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Purpose Perspectives of radiation oncologists on oligometastatic disease was investigated using multi-layered survey. Materials and Methods Online survey on the oligometastatic disease was distributed to the board-certified regular members of the Korean Society for Radiation Oncology. The questionnaire consisted of four domains: five questions on demographics; five on the definition of oligometastatic disease; four on the role of local therapy; and three on the oligometastatic disease classification, respectively. Results A total of 135 radiation oncologists participated in the survey. The median length of practice after board certification was 22.5 years (range, 1 to 44 years), and the vast majority (94.1%) answered affirmatively to the clinical experience in oligometastatic disease management. Nearly two-thirds of the respondents considered the number of involved organs as an independent factor in defining oligometastasis. Most frequently perceived upper limit on the numerical definition of oligometastasis was 5 (64.2%), followed by 3 (26.0%), respectively. Peritoneal and brain metastasis were nominated as the sites to be excluded from oligometastastic disease by 56.3% and 12.6% of the participants, respectively. Vast majority (82.1%) agreed on the role of local treatment in the management of oligometastatic disease. Majority (72%) of the participants acknowledged the European Society for Radiotherapy and Oncology (ESTRO)-European Organisation for Research and Treatment of Cancer (EORTC) classification of oligometastatic disease, however, only 43.3% answered that they applied this classification in their clinical practice. Underlying reasons against the clinical use were 'too complicated' (66.0%), followed by 'insufficient supporting evidence' (30.0%), respectively. Conclusion While most radiation oncologists supported the role of local therapy in oligometastatic disease, there were several inconsistencies in defining and categorizing oligometastatic disease. Continued education and training on oligometastatic disease would be also required to build consensus among participating caregivers. [ABSTRACT FROM AUTHOR]

The 2020 World Health Organization classification divided endocervical adenocarcinoma (ADC) into human papillomavirus–associated (HPVA) and human papillomavirus–independent (HPVI) ADCs. This multi-institutional study aimed to investigate the clinical features and prognosis of patients with endocervical ADC based on the updated World Health Organization classification. We retrospectively reviewed the 365 patients with endocervical ADC who underwent radical hysterectomy from 7 institutions. Tumor characteristics, patterns of failure, and survival outcomes were compared between HPVA and HPVI ADCs. Two hundred seventy-five (75.3%) and 90 (24.7%) patients had HPVA and HPVI ADC diagnoses, respectively. In all cases, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58.2% and 71.3%, respectively. HPVI ADC showed higher rates of local recurrence (25.6% vs 10.9%) and distant metastasis (33.3% vs 17.5%) than HPVA ADC. Multivariate survival analysis revealed that HPVI ADC showed significantly worse DFS (hazard ratio [HR], 1.919; 95% confidence interval [CI], 1.324-2.781; P <.001), distant metastasis-free survival (HR, 2.100; 95% CI, 1.397-3.156; P <.001), and OS (HR, 2.481; 95% CI, 1.586-3.881; P <.001) than HPVA ADC. Patients with gastric- and serous-type HPVI ADC had significantly worse OS than those with other HPVI ADCs (P =.020). Similarly, invasive stratified mucin-producing–type HPVA ADC showed significantly worse OS than other HPVA ADCs (P <.001). We demonstrated that HPVI ADC exhibited inferior DFS and OS and higher rates of local and distant recurrence compared with HPVA ADC. Gastric- and serous-type HPVI ADCs and invasive stratified mucin-producing–type HPVA ADC showed worse OS than other types of HPVI and HPVA ADCs, respectively. Our observation of significant differences in prognoses according to the histologic types needs to be validated in larger cohorts of patients with endocervical ADC. [ABSTRACT FROM AUTHOR]

Isoquercitrin (IQC) is a component abundantly present in many plants and is known to have an anti-viral effect against various viruses. In this study, we demonstrate that IQC exhibits strong anti-influenza A virus infection, and its effect is closely related to the suppression of hemagglutinin (HA) and neuraminidase (NA) activities. We used green fluorescent protein-tagged Influenza A/PR/8/34 (H1N1), A/PR/8/34 (H1N1), and HBPV-VR-32 (H3N2) to evaluate the anti-IAV effect of IQC. The fluorescence microscopy and fluorescence-activated cell sorting analysis showed that IQC significantly decreases the levels of GFP expressed by IAV infection, dose-dependently. Consistent with that, IQC inhibited cytopathic effects by H1N1 or H3N2 IAV infection. Immunofluorescence analysis confirmed that IQC represses the IAV protein expression. Time-of-addition assay showed that IQC inhibits viral attachment and entry and exerts a strong virucidal effect during IAV infection. Hemagglutination assay confirmed that IQC affects IAV HA. Further, IQC potently reduced the NA activities of H1N1 and H3N2 IAV. Collectively, IQC prevents IAV infection at multi-stages via virucidal effects, inhibiting attachment, entry and viral release. Our results indicate that IQC could be developed as a potent antiviral drug to protect against influenza viral infection. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify high-risk factors for regional recurrence in patients with breast cancer with pathologically negative lymph nodes.Methods and Materials: We retrospectively analyzed 3800 patients with stage pT1-pT3 breast cancer and pathologically negative lymph nodes between 2004 and 2012. All patients underwent upfront surgery with curative intent. Adjuvant systemic treatments were administered to most patients (96.7%) based on contemporary guidelines.Results: After a median follow-up of 83 months (range, 7-175 months), the estimated 10-year cumulative incidence rate of regional recurrence was 2.0%. Multivariate competing risk analysis revealed that high histologic grade, positive lymphovascular invasion, and stage pT2-3 were significant risk factors for any regional recurrence. Patients with ≥2 risk factors showed a significantly higher 10-year cumulative incidence rate of any regional recurrence than those with 1 or no risk factors (5.5% vs 1.2%; P < .001). When the number of retrieved lymph nodes was less than 10, the difference in the incidence rate of regional recurrence between patients with ≥2 risk factors and those with 1 or no risk factors was greater (6.6% vs 1.3%, respectively; P < .001). The 10-year disease-free survival was worse in patients with ≥2 risk factors than in those with 1 or no risk factors (84.7% vs 90.0%, respectively; P < .001). Patients with ≥2 risk factors also showed worse 10-year overall survival than did those with 1 or no risk factors (91.3% vs 97.0%, respectively; P < .001).Conclusions: Overall, the cumulative incidence rate of any regional recurrence was low at 10 years. However, patients with ≥2 risk factors showed an increased risk of any regional recurrence and worse disease-free survival, particularly when the number of retrieved lymph nodes was less than 10. [ABSTRACT FROM AUTHOR]

Objective: This multi-institutional study aimed to identify the optimal treatment strategy for small cell carcinoma of the cervix.Study Design: We retrospectively collected the medical records of 166 patients diagnosed with small cell carcinoma of the uterine cervix from January 2000 to December 2015 from 13 institutions of the Korean Radiation Oncology Group. After excluding 18 (10.8 %) patients who initially had distant metastasis, the treatment outcomes of 148 patients were analyzed.Results: After a median 46.4 (1.4-231.9) months of follow-up, the 5-year progression-free survival (PFS) and overall survival (OS) rates of all patients were 45.9 % and 63.5 %, respectively. Distant metastasis was the dominant pattern of failure occurring in 67 patients (45.3 %). We stratified the patients according to the primary local treatment: primary surgery (n = 119), primary radiotherapy (RT) (n = 26), and no local treatment group (n = 3). Although the primary RT group had advanced disease (FIGO stage ≧ IIB) more frequently than the primary surgery group (80.8 % vs. 47.9 %), the PFS and OS did not differ between the groups in multivariate analysis.Conclusion: Definitive RT is a reasonable local treatment option for small cell cervical cancer, particularly for advanced cases. Given the high rates of distant relapse, an effective systemic therapy protocol is warranted for small cell cervical cancer patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the impact of high-risk factors on the survival of patients with cervical cancer treated with surgery followed by adjuvant chemoradiotherapy. From 2000 to 2014, medical records of 897 patients with International Federation of Gynecology and Obstetrics stage IB–IIA disease treated with surgery were retrospectively reviewed. Among them, 483 patients with high-risk factors, including pelvic lymph node metastasis, parametrial invasion, or resection margin involvement, were analyzed. The median follow-up time was 57 months (range, 6–205 months). For patients with single and multiple high-risk factors, the 5-year DFS rates were 80.4% and 65.7%, respectively (p < 0.001), and 5-year OS rates were 87.3% and 75.1%, respectively (p = 0.001). Distant metastasis was the most common pattern of recurrence (86.1%). Furthermore, distant metastasis-free survival significantly differed with the number of high-risk factors present (single 82.7% vs. multiple 68.8%, p < 0.001). In the multivariate analysis, while parametrial invasion and resection margin involvement showed no association, the adenocarcinoma histology, pelvic lymph node metastasis, higher metastatic lymph node ratio, and multiple high-risk factors were independent prognosticators associated with poor DFS and OS. Patients with early-stage cervical cancer having multiple high-risk factors, adenocarcinoma histologic type, and pelvic lymph node metastasis accompanied by a higher lymph node ratio after surgery are more likely to have occult distant metastasis. Further, consolidation with systemic chemotherapy after adjuvant therapy might be considered to improve the survival outcome in this patient population. • We evaluated the impact of high-risk factors on the survival of patients with early-stage cervical cancer. • The presence of multiple high-risk factors was significantly associated with decreased survival outcomes. • Pelvic lymph node metastasis was the most significant prognosticators associated with disease recurrence and poor survival. • Consolidation with systemic chemotherapy after adjuvant therapy should be considered to improve the survival outcomes. [ABSTRACT FROM AUTHOR]

Highlights • Postoperative pulmonary complications occurred in 22.1% following neoadjuvant chemoradiotherapy and surgery for esophageal cancer. • Pre-radiotherapy FEV1 and mean lung dose were the most relevant risk factors for postoperative pulmonary complications. • Mean lung dose having 20% risk of pulmonary complications was 9.4 Gy and 7 Gy for those with FEV1 ≥ 2L and FEV1 < 2L, respectively. Abstract Background and purpose In locally advanced esophageal cancer, the optimal dose constraints for neoadjuvant chemoradiotherapy (NACRT) have yet to be established. This study is carried out to identify the most reliable dosimetric predictors for pulmonary complications following NACRT and surgery for esophageal cancer. Materials and methods We retrospectively reviewed the medical records of 308 patients with esophageal cancer who received surgery following NACRT for locally advanced esophageal cancer from January 2005 to June 2017. Dose–volume histograms (DVH) of both lungs were computed for each patient along with total lung volume, mean lung dose (MLD), V 5 , V 10 , V 20 , and V 30. The effect of each parameter on postoperative pulmonary complications was estimated in univariate and multivariate logistic regression analysis. Results Postoperative pulmonary complications occurred in 22.1% of all patients. Univariate analysis for pulmonary complications showed that location of tumor (P = 0.017), pre-RT FEV1 (P = 0.003), MLD (P = 0.002), V 5 (P < 0.001), V 10 (P < 0.001), and V 20 (P = 0.007) were all significant risk factors. Significant factors for postoperative pulmonary complications in multivariate analysis were MLD (odds ratio (OR) 1.118, 95% confidence interval (CI) 1.025–1.219, P = 0.012) and pre-RT FEV1 (OR 0.483, 95% CI 0.294–0.795, P = 0.004). Conclusions In patients who received NACRT and surgery for esophageal cancer, MLD was the parameter most related to postoperative pulmonary complications. Further studies are needed to establish the optimal DVH constraints for NACRT in order to minimize the risk of postoperative pulmonary complications in esophageal cancer patients. [ABSTRACT FROM AUTHOR]

• Thuja orientalis folium inhibits influenza A viral infection. • Thuja orientalis folium significantly inhibits influenza viral binding and entry to the cells by modulating hemagglutinin. • Thuja orientalis folium represses the neuraminidase activity of the influenza virus. • Thuja orientalis folium contains a strong virucidal effect at the early phase of viral infection. Thuja orientalis Folium (TOF) has been prescribed traditionally as an expectorant for inflammatory airway disease. In this study, we evaluated the anti-influenza A virus (IAV) activity of TOF by detecting GFP expressed by influenza A virus (A/PR/8/34-GFP) infection. The fluorescence microscopy and fluorescence-activated cell sorting analysis showed that TOF potently inhibited IAV infection, dose-dependently. Consistently, immunofluorescence and Q-PCR analysis results confirmed TOF significantly represses IAV protein and RNA expression. TOF inhibited IAV infection at the binding and entry step upon viral infection and interferes with HA protein. Further, TOF exhibited a virucidal effect and inhibited the neuraminidase activity of IAV. Additionally, TOF prevented the cytopathic effect caused by H1N1 and H3N2 IAV infection. Amentoflavone among the constituents in TOF exerted the strongest anti-IAV effect. Myricetin, quercetin, and quercitrin also inhibited IAV infection. However, the potent anti-IAV effect of TOF may be related to the synergistic effect of constituents, not by a single specific compound. Our results suggest TOF exhibits a significant inhibitory effect against IAV infection at multi-stages via the blockage of viral attachment and entry, inhibition of neuraminidase, and induction of virucidal effects. [ABSTRACT FROM AUTHOR]

Obesity and chronic kidney disease (CKD) are major global health problems. There are very little data concerning the prevalence and its associated factors of obesity in non-dialyzed patients who have different stages of CKD. Therefore, in this study, we examined the prevalence of obesity and its associated factors according to the stages of CKD. We used nationwide representative data from the Korean National Health and Nutrition Examination Survey, which was conducted over a 7-year period from 2008 to 2014 by the Korea Centers for Disease Control and Prevention. The results indicated that: (1) general obesity and abdominal obesity were more prevalent in patients with CKD compared to those without CKD; (2) the prevalence of general obesity and abdominal obesity was highest in stage 2 CKD; (3) stages 3a and 3b were the factors associated with general obesity, and stage 3a was significantly associated with abdominal obesity; (4) the association between general obesity/abdominal obesity and CKD disappeared in people with advanced stage 4/5 CKD; and (5) the presence of comorbidities contributed to the development of both general obesity and abdominal obesity. The findings of this study might support the idea that weight loss is a good potential intervention for the prevention of disease progression in moderate CKD (stage 3), but not severe CKD (stage 4/5). [ABSTRACT FROM AUTHOR]

Highlights: [•] Galla rhois extract showed a possibility of the antiplatelet activity. [•] Galla rhois extract suppressed ERK1/2 phosphorylation and PLCβ phosphorylation. [•] Galla rhois extract includes MG and PGG, as its components. [•] Methyl gallate (MG) inhibited the collagen-induced platelet activation. [•] Penta-O-galloyl-β-d-glucoside (PGG) inhibited thrombin-induced platelet activation. [Copyright &y& Elsevier]

A bstract Backgound: To compare differences in endoscopic revision after previously failed lacrimal surgery that involved either external or endoscopic dacryocystorhinostomy. Design: Retrospective, comparative, nonrandomized clinical study. Participants: We assessed 77 patients (82 surgeries) treated for recurrent nasolacrimal duct obstruction. Methods: Electronic medical records for patients with recurrent epiphora who underwent endoscopic revisional dacryocystorhinostomy, after previous external or endoscopic dacryocystorhinostomy at Seoul St. Mary's Hospital from 2004 to 2010, were reviewed. Main Outcome Measures: Data regarding the lacrimal drainage system, comprehensive eye examination, surgical outcome and preoperative/perioperative transnasal endoscopy were analysed. Results: In total, 77 patients underwent 82 endoscopic revisional dacryocystorhinostomy procedures. A success rate of 84% was achieved for cases of previous external dacryocystorhinostomy and 80.7% for previous endoscopic dacryocystorhinostomy ( P = 0.722). For preoperative nasal endoscopy, more of the patients who underwent previous external dacryocystorhinostomy exhibited a hypertrophic middle turbinate and severe septal deviation when compared with patients who underwent previous endoscopic dacryocystorhinostomy ( P = 0.031, P = 0.001, respectively). For perioperative nasal endoscopy, more of the patients who underwent previous endoscopic DCR exhibited a smaller ostium when compared with patients who underwent previous external dacryocystorhinostomy ( P = 0.031). Conclusions: The success rate of revisional dacryocystorhinostomy in the previous external dacryocystorhinostomy group was slightly higher than that in the previous endoscopic dacryocystorhinostomy group. Differences in preoperative and perioperative endoscopic findings were detected between the groups. Clarifying these differences in endoscopic revision will help improve the surgical outcomes of primary surgery involving either external or endoscopic dacryocystorhinostomy. [ABSTRACT FROM AUTHOR]

Abstract: Sosihotang (SO) is an herbal medication, which has been widely used to treat fever, chill and vomiting due to common cold in east-Asian countries. In this study, to provide insight into the effects of SO on inflammation, we investigated its effect on pro-inflammatory mediator production in RAW 264.7 cells and mouse peritoneal macrophages using lipopolysaccharide (LPS) stimulation. SO significantly inhibited the production of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin (IL)-6 as well as gene expression of inducible nitric oxide synthase (iNOS), its synthesizing enzyme. In addition, SO inhibited nuclear factor (NF)-κB activation and suppressed extracellular signal-regulated kinase (ERK), p38 and c- Jun NH2-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) phosphorylation. Furthermore, we found SO suppresses the production of NO and IL-6 in LPS-stimulated peritoneal macrophage cells. High performance liquid chromatography (HPLC) analysis showed SO contains many active anti-inflammatory constituents such as liquiritigenin, baicalin, baicalein, glycyrrhizin and wogonin. We first elucidated the inhibitory mechanism of SO on inflammation induced by LPS in macrophage cells. Our results suggest SO has potential to be developed as a therapeutic agent for various inflammatory diseases. [Copyright &y& Elsevier]

Silicone tube intubation (STI) has been known as a standard treatment modality with functional nasolacrimal duct obstruction (FNDO). Recently, dacryocystorhinostomy (DCR) is suggested for FNDO treatment. However, there are no data for comparison according to the surgical types in FNDO patients. This study aimed to compare success rates of three different lacrimal drainage surgeries in FNDO patients. Consecutive patients (153 eyes) who were treated with surgical intervention due to FNDO were analyzed. Patients were divided into three groups according to the type of surgery undertaken: STI, endoscopic DCR (Endo-DCR), and external DCR (Ext-DCR). Symptomatic improvements in epiphora were evaluated using the following scoring system: 1, complete resolution (indicative of success); 2, partial resolution; and 3, no resolution or worsening of the condition. At months 3 and 6, the Endo-DCR group had the highest success rate (84.4 and 81.3 %), but there were no statistically significant differences in epiphora scoring among the patients. Epiphora was significantly improved after surgery by week 2 in the Endo-DCR group ( p = 0.0339) and by week 3 in the STI group ( p = 0.0161). There were no patients in the Endo- or Ext-DCR group with a score of 3 at month 6, but 4 of 6 (3.7 %) in the STI group had score of 3 at month 6 and underwent additional DCR for epiphora. Our results suggest that Endo-DCR offers the highest success rates in FNDO treatments in terms of the rapid and complete resolution of epiphora. [ABSTRACT FROM AUTHOR]

In the present study, we evaluated the ophthalmologic outcomes of 24 patients who received chemotherapy and/or radiotherapy for the treatment of non-conjunctival ocular adnexal mucosa-associated lymphoid tissue-type (MALT) lymphoma. Ophthalmologic outcomes were assessed in patients who received chemotherapy and/or radiotherapy from March 2004 until May 2010. Outcomes were determined according to common symptoms following chemotherapy and/or radiotherapy, which consisted of decreased visual acuity, dry eye symptoms, retinopathy, optic neuropathy, increased intraocular pressure, and blepharitis. Nine patients received chemotherapy alone, eight patients received radiotherapy alone, and seven patients received chemotherapy with additional radiotherapy (chemoradiation therapy). Patients treated by chemotherapy alone showed better ophthalmologic outcome scores (mean score, 1.56) than those treated by radiation alone or chemoradiation therapy (mean score, 4.01). In conclusion, the treatment of ocular adnexal lymphoma including radiotherapy showed poor ophthalmologic outcomes due to radiation-induced complications. Recently, many new treatment options have emerged, such as immunotherapy or radioimmunotherapy. In the future study, to select a better treatment modality with fewer complications, well-designed prospective trials with ophthalmologic outcomes are needed. [ABSTRACT FROM AUTHOR]

Sipjeondaebotang (SJ) has been used as a traditional drug in east-Asian countries. In this study, to provide insight into the biological effects of SJ and SJ fermented by Lactobacillus, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in macrophages. The investigation was focused on whether SJ and fermented SJ could inhibit the production of pro-inflammatory mediators such as prostaglandin (PG) E2 and nitric oxide (NO) as well as the expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in LPS-stimulated RAW 264.7 cells. We found that SJ modestly inhibited LPS-induced PGE2, NO and TNF-α production as well as the expressions of COX-2 and iNOS. Interestingly, fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, fermented SJ exhibited increased inhibition of p38 MAPK and c-Jun NH2-terminal kinase (JNK) MAPK phosphorylation as well as NF-κB p65 translocation by reduced IκBα degradation compared with either untreated controls or unfermented SJ. High performance liquid chromatography (HPLC) analysis showed fermentation by Lactobacillus increases liquiritigenin and cinnamyl alcohol contained in SJ, which are known for their anti-inflammatory activities. Finally, SJ fermented by Lactobacillus exerted potent anti-inflammatory activity by inhibiting MAPK and NF-κB signaling in RAW 264.7 cells. [ABSTRACT FROM AUTHOR]

Abstract: Lycium Fruit has been used as a traditional drug for low back pain and chronic cough in east-Asian countries. However, inhibitory effects of Lycium Fruit water extract (LFWE) on inflammation remain unknown. In this study, we investigated the inhibitory effects of LFWE on pro-inflammatory mediator production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. LFWE inhibited LPS-induced nitric oxide (NO), prostaglandin (PG) E2, tumor necrosis factor (TNF)-α and interleukin (IL)-6 production as well as their synthesizing enzyme inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 gene expression. Furthermore, LFWE inhibited phosphorylations of extracellular signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) as well as suppression of IκBα degradation and nuclear translocation of nuclear factor (NF)-κB upon LPS stimulation. In addition, LFWE suppressed NO, PGE2, TNF-α and IL-6 production in LPS-stimulated peritoneal macrophage cells. Taken together, our results suggest that LFWE inhibits the production of various inflammatory mediators via blockade on the MAPKs and NF-κB pathways. This finding first explains the mechanism of anti-inflammatory effect by LFWE in LPS-stimulated macrophage cells. [Copyright &y& Elsevier]

Citrus Unshiu peel (CUP) has been traditionally used in East Asia as a drug for the treatment of vomiting and dyspepsia. However, its effects on inflammation remain unknown. In this study, we investigated the effects of CUP on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The research focused on determining whether CUP could inhibit the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and the activation of nuclear factor (NF)-κB, mitogen-activated protein kinases (MAPKs), as well as the secretion of nitric oxide (NO), prostaglandin (PG) E2, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in LPS-stimulated RAW 264.7 cells. We found that CUP represses LPS-induced iNOS and COX-2 gene expression as well as NO, PGE2, TNF-α and IL-6 production. Additionally, CUP inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK) MAPK, and suppressed IκBα degradation and nuclear translocation of NF-κB. Collectively, our results indicate that CUP inhibits the production of various inflammatory mediators via blockade of MAPK phosphorylation pursuant to the inhibition of IκBα degradation and the nuclear translocation of NF-κB. These findings are the first to clarify the mechanism underlying the anti-inflammatory effect exerted by CUP in RAW 264.7 macrophage cells stimulated by inflammatory agents. [ABSTRACT FROM AUTHOR]

Citrus Unshiu peel (CUP) has been traditionally used in East Asia as a drug for the treatment of vomiting and dyspepsia. However, its effects on inflammation remain unknown. In this study, we investigated the effects of CUP on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The research focused on determining whether CUP could inhibit the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and the activation of nuclear factor (NF)-κB, mitogen-activated protein kinases (MAPKs), as well as the secretion of nitric oxide (NO), prostaglandin (PG) E2, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in LPS-stimulated RAW 264.7 cells. We found that CUP represses LPS-induced iNOS and COX-2 gene expression as well as NO, PGE2, TNF-α and IL-6 production. Additionally, CUP inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK) MAPK, and suppressed IκBα degradation and nuclear translocation of NF-κB. Collectively, our results indicate that CUP inhibits the production of various inflammatory mediators via blockade of MAPK phosphorylation pursuant to the inhibition of IκBα degradation and the nuclear translocation of NF-κB. These findings are the first to clarify the mechanism underlying the anti-inflammatory effect exerted by CUP in RAW 264.7 macrophage cells stimulated by inflammatory agents. [ABSTRACT FROM AUTHOR]

The purpose of the study was to evaluate the clinical effects of bicanalicular double silicone stents in endoscopic transnasal dacryocystorhinostomy with lacrimal trephinized canaliculoplasty for monocanalicular and common canalicular obstruction. Bicanalicular double silicone intubation in endoscopic transnasal dacryocystorhinostomy with lacrimal trephination was performed in 58 eyes of 54 patients (5 men, 49 women; mean age: 55.9 ± 14.9 years) with epiphora due to monocanalicular and common canalicular obstruction between November 2007 and August 2010. We reviewed the records of subjects who had undergone the same surgery with a bicanalicular single intubation for same disease between March 2004 and October 2007 as controls (56 eyes of 50 patients). We evaluated age, gender, the operative side, the site of canalicular obstruction, and the effects of double silicone intubation. Complications relating to the silicone tube were also investigated. The double-stent group showed higher anatomical success rates (91.4%) and functional success rates (82.8%) than the single-stent group (75.0 and 69.6%, respectively) ( p = 0.034 and p = 0.103, respectively). Bicanalicular double silicone stenting in endoscopic transnasal dacryocystorhinostomy with lacrimal trephinized canaliculoplasty may be an effective treatment for monocanalicular and common canalicular obstructions. This may also reduce more invasive surgery including Jones tube insertion ( p = 0.038). [ABSTRACT FROM AUTHOR]

Epimedium koreanum Nakai (EKN) is a popular plant in Korean and Chinese medicine for treating a variety of ailments. The aqueous extract of EKN has a significant inhibitory impact on influenza A virus (IAV) infection by directly blocking viral attachment and having a virucidal effect, according to this study. Using fluorescent microscopy and fluorescence-activated cell sorting (FACS) with a green fluorescent protein (GFP)-tagged Influenza A/PR/8/34 virus, we examined the effect of EKN on viral infection. By viral infection, EKN strongly suppresses GFP expression, and at a dosage of 100 µg/mL, EKN decreased GFP expression by up to 90% of the untreated infected control. Immunofluorescence and Western blot analyses against influenza viral proteins revealed that EKN decreased influenza viral protein expression in a dose-dependent manner. EKN inhibited the H1N1 influenza virus's hemagglutinin (HA) and neuraminidase (NA), preventing viral attachment to cells. Furthermore, EKN had a virucidal impact and inhibited the cytopathic effects of H1N1, H3N2 and influenza B virus infection. Finally, our findings show that EKN has the potential to be developed as a natural viral inhibitor against influenza virus infection. [Display omitted] • Epimedium koreanum Nakai inhibits influenza viral infection. • Epimedium koreanum Nakai directly blocks influenza viral binding onto the cells. • Epimedium koreanum Nakai exhibited suppressive effects of neuraminidase and hemagglutinin of influenza virus. • Epimedium koreanum Nakai prevents cytopathic effect by H1N1, H3N2 IAV, and IBV infection and contains virucidal effect. [ABSTRACT FROM AUTHOR]

Solid tumors contain normoxic and hypoxic regions depending on the distance from the capillary. Normal cells may also be exposed to hypoxia under certain physiological conditions. Tumor hypoxia has been shown to associate strongly with tumor propagation and malignant progression. Hypoxia-inducible factor (HIF)-1α is stable under hypoxia and induces transcription of target genes by binding to the hypoxia-response element (HRE). Here we investigated the oncolytic effects of a novel adenovirus mutant with a deleted E1B55 gene (Ad.Δ55.HRE), in which the expression of E1A, which is essential for adenoviral replication, is regulated under the control of an HRE-expression system. Ad.Δ55.HRE expressed E1A under normoxia and more E1A under hypoxia and exhibited oncolytic effects on various cultured tumor cells, but its cytotoxic effect is relatively attenuated in normal fibroblast cells under normoxic and hypoxic conditions. Ad.Δ55.HRE lysed Huh-7 hepatoma cells stably expressing HIF-1α more effectively compared to parental cells. Ad.Δ55.HRE treatment exhibited significant antitumor activity in PC-3 prostate- and MDA-MB-435 breast tumor-bearing nude mice in which HIF-1α protein was immunohistochemically detected. The E1A and hexon proteins of adenovirus were immunostained in MDA-MB-435 xenografts after Ad.Δ55.HRE treatment, suggestive of viral replication. Our results suggest that Ad.Δ55.HRE may be useful for the treatment of solid tumors. [Copyright &y& Elsevier]

We determined the effects of two extracts from Acer palmatum Thumb. leaves (hot water extract KIOM-2015EW and 25% ethanol extract KIOM-2015EE) in a benzalkonium chloride (BAC)-induced dry eye mouse model. Dry eye was induced by 0.2% BAC for 2 weeks, followed by treatment three times (eye drop) or once (oral administration) daily with KIOM-2015E for 2 weeks. Treatment with both KIOM-2015EE and KIOM-2015EW resulted in a marked increase in tear volume production for the 4 days of treatment. The Lissamine Green staining score, TUNEL-positive cells, and inflammatory index were significantly decreased after 2 weeks. Topical KIOM-2015EE administration exhibited a greater improvement in decreasing the ocular surface staining scores, inflammation, dead cells, and increasing tear production in a dose-dependent manner compared with the other groups. Furthermore, KIOM-2015E significantly reduced the phosphorylation of NF-κB, which was activated in the BAC-treated cornea. Topical administration was much more effective than oral administration for KIOM-2015E and KIOM-2015EE was more effective than KIOM-2015EW. Application of KIOM-2015E resulted in clinical improvement, inhibited the inflammatory response, and alleviated signs of dry eye. These results indicate that KIOM-2015E has potential as a therapeutic agent for the clinical treatment of dry eye. [ABSTRACT FROM AUTHOR]

Introduction: Although positron‐emission tomography (PET) plays an integral role in cervix cancer diagnosis, there are limited data on PET‐based image‐guided brachytherapy (IGBT). We aimed to report the long‐term outcomes of PET‐based IGBT. Methods: We reviewed 151 patients treated with definitive radiotherapy (RT), including PET‐based IGBT between 2009 and 2018. After median 45 Gy of external beam RT with the four‐field technique, a median 24 Gy of high‐dose‐rate iridium‐192 IGBT was delivered in six fractions with Fletcher‐Suit tandem and ovoids. All patients underwent 18F‐fluorodeoxyglucose‐PET/computed tomography planning with a brachytherapy applicator. Multivariable analysis of local control (LC) was performed using Cox regression analysis. Results: The median high‐risk clinical target volume (HRCTV) and HRCTV D90% were 51.8 (interquartile range [IQR] 35.9–79.4) cm3 and 77.7 (IQR 74.7–81.2) Gy, respectively. With a median follow‐up of 57 (IQR 24.3–81.4) months, the 5‐year LC rate was 89.2%. HRCTV ≥72 cm3 was associated with inferior LC (hazard ratio, 3.72, p =.017) after multivariable analysis: the 5‐year LC rates were 94.0% and 77.9% for HRCTVs ≥72 and < 72 cm3, respectively (p =.002). The impact of HRCTV D90% ≥70 Gy on LC was significant in patients with an HRCTV ≥72 cm3 compared to that in those with HRCTV < 72 cm3. Patients with adeno/adenosquamous carcinoma demonstrated inferior LC in both groups. There were 13 (8.6%) and 11 (7.3%) patients with acute and late severe toxicities after RT. Conclusion: PET‐based IGBT leads to favorable LC, and HRCTV ≥72 cm3 requires further dose escalation to improve outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prognostic significance of tumor regression rate according to radiation phase and histologic subtype in patients with locally advanced cervical cancer (LACC) treated with chemoradiation. We retrospectively reviewed the medical records of 398 patients with FIGO stage IIB-IVA cervical cancer treated with concurrent chemoradiotherapy (CCRT) between 2001 and 2019. Tumor response was assessed using serial magnetic resonance imaging (MRI) at three time points: pre-treatment, post-external beam radiotherapy (EBRT), and post-intracavitary radiotherapy (ICR). Tumor regression pattern according to histologic subtype and radiation phase (EBRT and ICR) was evaluated. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Of 398 patients, 44 patients had adenocarcinoma/adenosquamous carcinoma (AC/ASC) and 354 patients had squamous cell carcinoma (SCC). AC/ASC was associated with significantly worse PFS and OS than SCC (p < 0.001). AC/ASC had a relatively poorer regression rate in response to EBRT than SCC (p < 0.001), whereas there was no significant difference in overall tumor regression rate after completion of RT (EBRT and ICR) between the two histologic subtypes. Multivariable analysis demonstrated AC/ASC histology to be an independent prognostic factor of decreased PFS and OS. Moreover, tumor regression rate after completion of EBRT (post-EBRT tumor regression rate (EBRTregression ≤ 26%) and proportion of tumor regression during EBRT to overall tumor regression (EBRTproportion ≤ 40%) were independent predictors of poor survival in patients with LACC. Tumor regression pattern of LACC in response to CCRT differs according to histologic subtype. AC/ASC histology and poor tumor response to EBRT are independent prognostic factors for worse survival in patients with LACC. Further studies are needed to develop a CCRT protocol that is specialized for patients with AC/ASC. [ABSTRACT FROM AUTHOR]

Due to a superior dose conformity to the target, proton beam therapy (PBT) continues to rise in popularity. Recently, considerable efforts have been directed toward discovering treatment options for use in combination with PBT. This study aimed to investigate the targeting of checkpoint kinase 1 (CHK1), a critical player regulating the G2/M checkpoint, as a promising strategy to potentiate PBT in human triple-negative breast cancer (TNBC) cells. Protons induced cell-cycle arrest at the G2/M checkpoint more readily in response to increased CHK1 activation than X-rays. A clonogenic survival assay revealed that CHK1 inhibition using PF-477736 or small interfering RNA (siRNA) enhanced the sensitivity toward protons to a greater extent than toward X-rays. Western blotting demonstrated that PF-477736 treatment in the background of proton irradiation increased the pro-apoptotic signaling, which was further supported by flow cytometry using annexin V. Immunofluorescence revealed that proton-induced DNA double-strand breaks (DSBs) were further enhanced by PF-477736, which was linked to the downregulation of Rad51, essential for the homologous recombination repair of DSBs. Direct inactivation of Rad51 resulted in enhanced proton sensitization. Collectively, these data suggest that targeting CHK1 may be a promising approach for improving PBT efficacy in the treatment of TNBC. [ABSTRACT FROM AUTHOR]

Background: Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. Methods: We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6–9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0–29.9%, 30–49.9%, 50–69.9%, 70–79.9%, 80–89.9%, and 90–100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. Results: Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. Conclusion: For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume. [ABSTRACT FROM AUTHOR]

Purpose This study aims to determine the association between pre- and postoperative radiotherapy (PORT) circulating tumor DNA (ctDNA) dynamics and oncological outcomes in patients with residual triple-negative breast cancer who underwent surgery after neoadjuvant chemotherapy (NAC). Materials and Methods Between March 2019 and July 2020, 11 nonmetastatic patients with residual disease who underwent surgery after NAC were prospectively enrolled. In each patient, tumor specimens obtained during surgery and blood samples collected at three time points during PORT (T0: pre-PORT, T1: 3 weeks after PORT, T2: 1 month after PORT) were sequenced, targeting 38 cancerrelated genes. Disease-free survival (DFS) was evaluated and the association between DFS and ctDNA dynamics was analyzed. Results At T0, ctDNA was detected in three patients (27.2%). The ctDNA dynamics were as follows: two showed a decreasing ctDNA variant allele frequency (VAF) and reached zero VAF at T2, while one patient exhibited an increasing VAF during PORT and maintained an elevated VAF at T2. After a median follow-up of 48 months, two patients experienced distant metastasis without any locoregional failures. All failures occurred in patients with ctDNA positivity at T0 and a decreased VAF after PORT. The 4-year DFS rates according to the T0 ctDNA status were 67% (positive ctDNA) and 100% (negative ctDNA) (p=0.032). Conclusion More than a quarter of the patients with residual disease after post-NAC surgery exhibited pre-PORT ctDNA positivity, and ctDNA positivity was associated with poor DFS. For patients with pre-PORT ctDNA positivity, the administration of a more effective systemic treatment should be considered. [ABSTRACT FROM AUTHOR]

A correction to the article "Epimedium Koreanum Nakai Displays Broad Spectrum of Antiviral Activity In Vitro and In Vivo by Inducing Cellular Antiviral State" which was published in a previous issue is presented.

Incidental pulmonary nodules detected via computed tomography (CT) are usually small, solid nodules (diameters less than 8 mm) that are likely benign and are difficult to biopsy. Additional features of the benignity of these small nodules may help determine the need and periodicity of further follow-up and should be identified. This study was conducted to examine the clinical factors associated with benign solid pulmonary nodules measuring less than 8 mm in diameter. This retrospective study enrolled participants who underwent low-dose chest CT scans for 3 consecutive years during routine health check-ups at a university hospital in Korea. We chose a 2-year study period to ensure that the nodule(s) were benign, which meant there was no interval change over this period. Participants were stratified into two groups: no nodule (n = 56) and nodule(s) (n = 355). Multivariable logistic regression analyses were performed to explore associations (adjusted odds ratio [aOR], 95% confidence interval [CI], p-value) between variables and nodule(s). In this study cohort, elevated levels of low-density lipoprotein (LDL) cholesterol were positively associated factors with the presence of benign pulmonary nodule(s) (aOR: 1.10, 95% CI:1.00–1.20, p = 0.0488), whereas current cigarette smoking was negatively associated with nodules (aOR: 0.26, 95% CI: 0.08–0.81, p = 0.0202). Therefore, an elevated LDL cholesterol level was the only factor that was positively associated with the presence of benign small pulmonary nodules. [ABSTRACT FROM AUTHOR]

Aim Of the Review: Use of smart devices to provide real-time cardiopulmonary resuscitation (CPR) feedback in the context of out-of-hospital cardiac arrest (OHCA) has considerable potential for improving survival. However, the findings of previous studies evaluating the effectiveness of these devices have been conflicting. Therefore, we conducted a systematic review of the literature to assess the utility of smart devices for improving the quality of CPR during CPR training.Data Sources: Thirteen electronic databases were searched. The articles were reviewed according to the eligibility criteria. CPR quality was evaluated based on the rates and depths of chest compression, and the proportion of adequate depth of chest compressions.Results: Ultimately, 11 studies (5 randomised controlled trials, 1 randomised trial, and 5 randomised cross-over trials) were selected for this systematic review. Eight of these studies used smartphones and three used smartwatches. This review did not find an apparent benefit from smart device use during CPR in terms of maintaining the recommended compression rates and depths of chest compressions. However, all three smartwatch studies reported that the proportion of chest compressions of adequate depth was significantly improved with smartwatch use (smartwatch group vs. non-smartwatch group in the three studies: 65.01% vs. 45.15%, p = 0.01; 64.6% vs. 43.1%, p = 0.049; 98.7% vs. 79.3%, p = 0.002).Conclusion: This review does not find durable evidence for usefulness of smart devices in CPR training. However, the smartwatches may improve the accuracy of chest compression depth. Future studies with larger sample sizes might be necessary before reaching a firm conclusion. [ABSTRACT FROM AUTHOR]

Hoveniae semen seu fructus (HSF, fruit and seed of Hovenia dulcis Thunb) is an important traditional herbal medicine and food supplement in East Asia for the treatment of liver diseases, alcohol poisoning, obesity, allergy, and cancer. HSF has also been reported to have anti-inflammatory activity, but the cellular mechanism of action is not fully understood. We assessed the anti-inflammatory properties of an HSF ethanol (HSFE) extract and explored its precise mechanism. The ability of HSFE to suppress inflammatory responses was investigated in a murine macrophage cell line, RAW 264.7, and mouse primary macrophages. Secretions of NO, proinflammatory cytokines, inflammatory factors, and related proteins were measured using the Griess assay, ELISA, Western blot analysis, and real-time PCR, respectively. In addition, the main components of HSFE were analyzed by HPLC, and their anti-inflammatory activity was confirmed. Our results showed that pretreatment of HSFE markedly reduced the expression of NO and iNOS without causing cytotoxicity and significantly attenuated secretion of proinflammatory cytokines, including TNF-α, IL-6, and IL-1β. In addition, HSFE strongly suppressed phosphorylation of MAPK and decreased the activation of AP-1, JAK2/STAT, and NF-κB in LPS-stimulated RAW 264.7 cells in a concentration-dependent manner. Furthermore, HSFE strongly suppressed the inflammatory cytokine levels in mouse peritoneal macrophages. Also, as a result of HPLC analysis, three main components, ampelopsin, taxifolin, and myricetin, were identified in the HSFE extract, and each compound effectively inhibited the secretion of inflammatory mediators induced by LPS. These findings show that HSFE exerts anti-inflammatory effects by suppressing the activation of MAPK, AP-1, JAK2/STAT, and NF-κB signaling pathways in LPS-stimulated macrophages. In addition, the anti-inflammatory efficacy of HSFE appears to be closely related to the action of the three main components. Therefore, HSFE appears to be a promising candidate for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Purpose: To investigate possible correlations between blepharoptosis and pterygium in a nationally representative sample of the Korean population.Methods: This population-based, cross-sectional study was comprised of 3,685 males and 4,792 females (≥ 19 years of age) participating in the fifth annual Korea National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2012. The enrolled subjects underwent interviews, clinical examinations, and laboratory tests. Statistical tests were used to compare the prevalence of blepharoptosis, according to pterygium subtypes or pterygium existence. Multiple logistic regression analyses were also used to find the associations of blepharoptosis with pterygium.Results: Pterygium was present in 10.3% of males and 9.8% of females. The odds ratios (ORs) of pterygium in Korean males significantly decreased as the severity of blepharoptosis increased (p for trend = 0.0252). Using three models in multivariate analyses, males with blepharoptosis had an OR (95% confidence interval, (CI)) of 0.643 (0.435 ~ 0.951) for pterygium compared with males with no blepharoptosis, after adjusting for age, body mass index, smoking status, alcohol consumption, physical activity, serum vitamin D levels, diabetes mellitus, metabolic syndrome, high blood pressure, and stress intolerance. There was no significant association between blepharoptosis and females.Conclusions: The association between blepharoptosis and pterygium in the Korean population showed a gender difference. Epidemiologic evidence only showed a negative correlation between blepharoptosis and pterygium in Korean males. Further studies are needed, therefore, to examine the sex difference in the pathogenesis of pterygium. [ABSTRACT FROM AUTHOR]

Simple Summary: With the development of modern systemic therapy, the role and indications of PMRT need to be further investigated in early-stage N1 breast cancer patients who have received upfront mastectomy, as recent guidelines still do not reach a consensus. Our study aimed to identify risk factors that may worsen treatment outcomes, and found that three lymph node metastases were prognostic for loco-regional control (LRC), disease-free survival (DFS), and lympho-vascular invasion (LVI) for overall survival (OS). However, the benefit of PMRT was not evident even in patients with these risk factors, and the results were similar after propensity score matching. Moreover, the incidence of arm lymphedema was significantly higher after PMRT. Therefore, we cautiously suggest omitting PMRT in T1-2N1 breast cancer patients, given the similar oncologic outcomes and increased risk of RT-related toxicity after PMRT. This study aimed to evaluate the role of post-mastectomy radiotherapy (PMRT) in T1-2N1 breast cancer. Between 2006 and 2014, a total of 504 patients with T1-2N1 breast cancer were analyzed. PMRT was administered to 71 patients, and 1:2 propensity score matching (PSM) was performed between the PMRT and non-PMRT groups. Loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were compared according to PMRT status. Thirteen and one loco-regional recurrences were observed in the PMRT and non-PMRT groups, respectively. Before PSM, the 8-year LRC, DFS, and OS rates in the non-PMRT and PMRT groups were 98.5% and 96.5% (p = 0.426), 89.7% and 91.2% (p = 0.700), and 91.5% and 92.1% (p = 0.679), respectively. Corresponding rates were 95.6% and 96.5% (p = 0.365), 84.1% and 91.2% (p = 0.185), and 88.4% and 92.1% (p = 0.276), respectively, after PSM. Multivariate analysis showed that three lymph node metastases were prognostic for LRC and DFS rates and LVI for OS rate. Arm lymphedema developed in 32.4% of patients who received PMRT, which was significantly higher than the non-PMRT group (p < 0.001). Contributions of PMRT for improvement of treatments outcomes in T1-2N1 breast cancer patients were not evident, while the incidence of arm lymphedema significantly increased after PMRT. Further prospective trials are required to re-evaluate the role of PMRT. [ABSTRACT FROM AUTHOR]

Aim: Patients with locoregionally uncontrolled breast tumors are frequently referred for breast palliative radiotherapy (PRT) to mitigate symptoms. We analyzed the outcomes following breast PRT to optimize PRT according to risk groups. Methods: We reviewed 133 patients who underwent breast PRT. A median total dose of 45 Gy was prescribed with an equivalent dose in 2 Gy fractions (EQD2, α/β = 3.5) of 53 Gy. The Cox proportional hazards model was used to analyze the prognostic factors of local control (LC). Results: Most (90.2%) had polymetastatic disease (> 5 lesions), and 48.9% had bone metastasis. With a median follow-up of 17.2 months, the 2-year LC and overall survival (OS) rates were 49.4%, and 48.3%, respectively. Multivariable analyses demonstrated progressive or mixed responses outside the breast and > 2 lines of previous therapy as adverse features for clinical outcomes. Group 1 (0 risk factors) showed favorable 2-year LC and OS of 63.9%, and 72.8%, respectively, whereas group 3 (2 risk factors) showed the worst outcomes of 0%, and 6.8%, respectively. Breast PRT with EQD2 ≥ 63 Gy showed a significant benefit in LC for group 1 and marginal benefit (p = 0.055) for group 2, but no improvement for group 3 (p = 0.300). Conclusion: Breast PRT showed favorable LC outcomes in patients with stable disease outside the breast and treated with ≤ 2 lines of systemic treatment. Our findings warrant future clinical trials investigating the role of higher than palliative dose and early intervention of PRT in stage IV patients. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 22-year-old man with massive hemoptysis who undergo mechanical ventilation and intubation. It states that using emergency bronchoscopy, he was diagnosed of widespread blood clots. It says that several of his cylindrical clots were taken out through suctioning, which caused his tidal volume to rise to 400 milliliter (ml) and oxygen saturation to the upper 80s. It explains that endobronchial obstruction by blood clots causes airway obstruction.

Enzymatic browning is a major issue that needs to be solved in the food industry. Although swertiajaponin is a flavonoid rich in the whole herb of Swertia japonica that has been clinically used, its biological functions and applicat​ion in the foods have not been fully elucidated. Here, we showed that swertiajaponin efficiently blocked enzymatic browning in potatoes possibly by direct binding to and inactivating polyphenol oxidase. Furthermore, swertiajaponin showed potent antioxidant activity proven by markedly suppressed reactive oxygen species. Swertiajaponin significantly increased antioxidant properties of potato extract when it is added since it additively elevated total flavonoid content. Considering numerous beneficial effects of antioxidants, swertiajaponin may be used as a functional food additive to suppress enzymatic browning and elevate the antioxidant capacity of foods including beverages and soups by fortification of flavonoids. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Dianthi Herba is a traditional herbal medicine used to treat inflammatory-related diseases including acute pyelonephritis, cystitis, laryngopharyngitis, and urethritis. Aim of the study We investigated the effects of Dianthi Herba ethanolic extract (DH) on lipopolysaccharide (LPS)-mediated inflammatory responses in murine macrophages including RAW 264.7 cell line and mouse peritoneal macrophages as well as nociceptive and edema mouse models. Materials and methods The biological effects of DH on inflammatory cytokine, mediator, and related protein production were assessed using enzyme-linked immunosorbent assay (ELISA), Western blotting, and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). Additionally, Western blotting was performed to investigate intracellular signaling pathways, and the anti-nociceptive activity of three doses of DH (100, 200, and 300 mg/kg) against acetic acid-induced writhing responses and its inhibitory effects on xylene-induced ear edema were researched in mice through oral administration. Results DH treatment significantly inhibited nitric oxide (NO) secretion and inflammatory cytokine production in RAW 264.7 cells and mouse peritoneal macrophages and induced heme oxygenase (HO)−1 expression. DH strongly inhibited the transcriptional activity of nuclear factor (NF)-κB and phosphorylation of mitogen-activated protein kinases (MAPK) in LPS-stimulated macrophages. Meanwhile, DH exerted anti-nociceptive effects on writhing responses and anti-edema effects in mice. Conclusion We confirmed the anti-inflammatory activities and inhibitory mechanism of DH in macrophages and clarified its inhibitory effects in vivo. These findings illustrate the therapeutic potential of DH as a natural anti-inflammatory agent. [ABSTRACT FROM AUTHOR]

Background Retinopathy and left ventricular hypertrophy (LVH) are representative markers of microvascular and cardiac dysfunction in patients with chronic kidney disease (CKD). However, their relationship and their combined effects on clinical outcomes are unknown. Methods We included 401 patients with nondialysis-dependent CKD stage 3–5 who had been examined with fundus photography for diabetic or hypertensive retinopathy. The presence of LVH was identified by echocardiography. The clinical significance of retinopathy and LVH was evaluated in terms of the rate of renal function decline and for any cardiovascular event (CVE)/death. Results CKD patients with retinopathy had a higher prevalence of LVH than those without retinopathy (38.9% vs. 27.6%, P = 0.017). The presence of retinopathy was independently associated with LVH (odds ratio 1.69, 95% confidence interval [CI] 1.02, 2.80). Compared with subjects without either retinopathy or LVH, the coexistence of retinopathy and LVH was independently associated with rapid renal function decline (β = − 3.28; 95% CI − 6.52, − 0.04), whereas retinopathy or LVH alone were not. Patients with both retinopathy and LVH had a higher risk of CVE/death (adjusted hazard ratio 2.75; 95% CI 1.44, 5.26) than patients with either factor alone. A significant synergistic interaction was observed between retinopathy and LVH to predict CVE/death ( P for interaction = 0.049). Conclusions Retinopathy was independently associated with LVH. The coexistence of retinopathy and LVH was associated with higher risks of CKD progression and CVE/death than was either factor alone, and their combined effects synergized to predict the risk of CVE/death. [ABSTRACT FROM AUTHOR]

Lilii Bulbus, the bulb of tiger lily, has anti-oxidant and anti-tumorigenic properties. However, the effects of Lilii Bulbus on learning, memory, and hippocampal neurogenesis remain unknown. This study investigated whether water extract of Lilii Bulbus (WELB) affects memory ability and hippocampal neurogenesis. Behavioral analyses (Morris water maze and passive avoidance test), immunohistochemistry, cell proliferation assay, and immunoblot analysis were performed. WELB (50 and 100 mg/kg; for 14 days) enhanced memory retention and spatial memory in normal mice as well as in scopolamine-treated mice with memory deficits. Furthermore, the administration of WELB significantly increased the number of proliferating cells and surviving newborn cells in the dentate gyrus of the hippocampus in normal mice. We found that WELB has a pro-neurogenic effect by increasing the activation of brain-derived neurotrophic factor (BDNF)/cAMP response element-binding protein (CREB) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) in the hippocampus. Moreover, we confirmed that WELB (100 and 200 μg/ml) significantly increased NE-4 C and primary embryonic NSCs proliferation. Inhibition/knockdown of MEK/ERK blocked WELB-induced MEK/ERK phosphorylation and NSCs proliferation. Hence, MEK/ERK activation was required in WELB-induced NSCs proliferation. Our study demonstrates the first evidence for WELB promoting hippocampal neurogenesis and memory; pro-neurogenic activity may enhance brain plasticity, with implications for treating neurodegenerative diseases. [Display omitted] • WELB enhances hippocampus-dependent learning and memory in normal and scopolamine-induced memory deficits mice. • WELB promotes hippocampal neurogenesis in normal mice. • MEK/ERK/BDNF/CREB activation was required for WELB-induced NSCs proliferation. • WELB has the pro-neurogenic effects on memory and neurogenesis in the hippocampus. [ABSTRACT FROM AUTHOR]

Isatidis folium or Isatis tinctoria L. is a flowering plant of the Brassicaceae family, commonly known as woad, with an ancient and well-documented history as an indigo dye and medicinal plant. This study aimed to evaluate the anti-atopic dermatitis (AD) effects of Isatidis folium water extract (WIF) using a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model and to investigate the underlying mechanism using tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-activated HaCaT cells. Oral administration of WIF reduced spleen weight, decreased serum IgE and TNF-α levels, reduced epidermal and dermal thickness, and inhibited eosinophil and mast cell recruitment to the dermis compared to DNCB-induced control groups. Furthermore, oral WIF administration suppressed extracellular signal-regulated kinase and p38 mitogen-activated protein kinase protein expression levels, p65 translocation from the cytoplasm to the nucleus, and mRNA expression of TNF-α, IFN-γ, interleukin (IL)-6, and IL-13 in skin lesion tissues. In HaCaT cells, WIF suppressed the production of regulated upon activation, normal T cell expressed and secreted (RANTES), thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), MCP-1, and MIP-3a, which are inflammatory cytokines and chemokines related to AD, and inhibited the mRNA expression of RANTES, TARC, and MDC in TNF-α/IFN-γ-stimulated HaCaT cells. Overall, the results revealed that WIF ameliorated AD-like skin inflammation by suppressing proinflammatory cytokine and chemokine production via nuclear factor-κB pathway inhibition, suggesting WIF as a potential candidate for AD treatment. [ABSTRACT FROM AUTHOR]

Rhapontici Radix (RR) has been used in traditional medicine in East Asia and has been shown to have various beneficial effects. However, its biological properties or mechanism on inflammation-related diseases is unknown. The goal of this study was to determine the anti-inflammatory activity and underlying molecular mechanisms of Rhapontici Radix ethanol extract (RRE). The inhibitory effect of RRE on the production of NO, cytokines, inflammatory-related proteins, and mRNAs in LPS-stimulated macrophages was determined by the Griess assay, ELISA, Western blot analysis, and real-time RT-PCR, respectively. Our results indicate that treatment with RRE significantly inhibited the secretion of NO and inflammatory cytokines in RAW 264.7 cells and mouse peritoneal macrophages without cytotoxicity. We also found that RRE strongly suppressed the expression of iNOS and COX-2 and induced HO-1 expression. It also prevented nuclear translocation of NF-κB by inhibiting the phosphorylation and degradation of IκBα. Furthermore, the phosphorylation of MAPKs in LPS-stimulated RAW 264.7 cells was significantly inhibited by RRE. These findings suggest that RRE may operate as an effective anti-inflammatory agent by inhibiting the activation of NF-κB and MAPK signaling pathways and inducing HO-1 expression in macrophages. Our results suggest that RRE has potential value as candidate to inflammatory therapeutic phytomedicine. [ABSTRACT FROM AUTHOR]

Sanguisorbae Radix (SR) is well known as herbal medicine named “Zi-Yu” in Korea, which is the dried roots of Sanguisorba officinalis L. (Rosacease). We investigated the underlying mechanism on the inhibition of atopic dermatitis (AD) of an ethanol extract of SR (ESR) using 2,4-dinitrochlorobenzene- (DNCB-) induced AD mice model. Oral administration of ESR significantly suppressed DNCB-induced AD-like symptoms such as scratching behavior, ear thickness, epidermal thickness, and IgE levels. To investigate the effects of ESR treatment on degranulation of IgE/Ag-activated mouse bone marrow-derived mast cells (BMMCs), we measured the release of β-hexosaminidase (β-HEX, degranulation marker). ESR decreased the infiltration of eosinophils and mast cells into the AD skin lesions. Furthermore, ESR significantly inhibited degranulation of IgE/Ag-activated BMMCs. We have demonstrated that ESR decreased AD symptoms in mice and inhibits degranulation of IgE/Ag-activated mast cells. Our study suggests that ESR may serve as a potential therapeutic candidate for the treatment of AD symptoms. [ABSTRACT FROM AUTHOR]

Background: The Korean Radiation Oncology Group (KROG) 19 - 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run.Methods: Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans.Results: We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss's kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans.Conclusion: We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 - 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 - 09 study results. [ABSTRACT FROM AUTHOR]

This study investigated the antioxidant activity of one hundred kinds of pure chemical compounds found within a number of natural substances and oriental medicinal herbs (OMH). Three different methods were used to evaluate the antioxidant activity of DPPH radical-scavenging activity, ABTS radical-scavenging activity, and online screening HPLC-ABTS assays. The results indicated that 17 compounds exhibited better inhibitory activity against ABTS radical than DPPH radical. The IC50 rate of a more practical substance is determined, and the ABTS assay IC50 values of gallic acid hydrate, (+)-catechin hydrate, caffeic acid, rutin hydrate, hyperoside, quercetin, and kaempferol compounds were 1.03 ± 0.25, 3.12 ± 0.51, 1.59 ± 0.06, 4.68 ± 1.24, 3.54 ± 0.39, 1.89 ± 0.33, and 3.70 ± 0.15 μg/mL, respectively. The ABTS assay is more sensitive to identifying the antioxidant activity since it has faster reaction kinetics and a heightened response to antioxidants. In addition, there was a very small margin of error between the results of the offline-ABTS assay and those of the online screening HPLC-ABTS assay. We also evaluated the effects of 17 compounds on the NO secretion in LPS-stimulated RAW 264.7 cells and also investigated the cytotoxicity of 17 compounds using a cell counting kit (CCK) in order to determine the optimal concentration that would provide an effective anti-inflammatory action with minimum toxicity. These results will be compiled into a database, and this method can be a powerful preselection tool for compounds intended to be studied for their potential bioactivity and antioxidant activity related to their radical-scavenging capacity. [ABSTRACT FROM AUTHOR]

Epimedium Herb (EH) is a medicinal herb used in traditional Eastern Asia. In this study described, we investigated the biological effects of Epimedium Herb water extract (EHWE) on lipopolysaccharide (LPS)-mediated inflammation in macrophages and local inflammation in vivo. We also investigated the biological effects of EHWE on the production of inflammatory mediators, pro-inflammatory cytokines and related products, as well as nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) activation in LPS-stimulated macrophages. The analgesic effect of the acetic acid-induced writhing response and inhibitory activity on xylene-induced ear edema was also evaluated in mice. EHWE exhibited anti-inflammatory effects by inhibiting the production of nitric oxide (NO), interleukin (IL)-6 and IL-1β. In addition, EHWE strongly suppressed inducible nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO-1) expression, and inhibited NF-κB activation as well as MAPK pathway phosphorylation. Furthermore, EHWE exhibited an analgesic effect on the writhing response and an inhibitory effect on ear edema in mice. For the first time, we demonstrated the anti-inflammatory effects and inhibitory mechanism in macrophages, as well as the inhibitory activity of EHWE in vivo. Our results indicate a potential use of EHWE as an inflammatory therapeutic agent developed from a natural substance. [ABSTRACT FROM AUTHOR]

A systematic search for eyelid angiosarcoma was performed from inception to December 2020 in Medline, EMBASE, and the Cochrane databases. Forty two eyelid angiosarcoma cases in 32 articles were analyzed. Eyelid angiosarcomas showed an incidence peak in the eighth decade of life, and was reported more frequently in Caucasian males. Eyelid angiosarcomas were associated with a mortality rate of 26.2%, a recurrence rate of 14.3%, and a cure rate of 45.2%. Four years event-free survival (EFS) rate was 36.0%, with median EFS of 36 months. Eyelid angiosarcomas with bilateral involvement or metastasis showed higher mortality and recurrence rates than unilateral eyelid invasion cases. In the prognosis analysis according to treatment modalities, the mortality and recurrence rates were the lowest in patients who underwent surgical excision. The 4-year EFS probability in a group with surgical excision was 60.6%, but in a group without surgical excision it was 30.3%. A total of 45.2% of the cases was misdiagnosed and 21.4% of the cases could not be correctly diagnosed with the first biopsy trial. The prognosis for eyelid angiosarcomas was better than that of angiosarcomas invading the face and scalp. Surgical excision was the most important treatment modality; thus, should be considered as the first treatment of choice. [ABSTRACT FROM AUTHOR]

Background: Isatis tinctoria L (PLG) is a medicinal herb from the roots of Isatis indigotica Fort (Family Cruciferae). Previous studies have shown that PLG has anti-inflammatory and therapeutic effects against conditions such as acute and chronic hepatitis, various respiratory inflammations, and cancer. The purpose of this study was to define the pharmacological effects of PLG on inflammatory reactions and skin hyperkeratosis, which are the main symptoms of atopic dermatitis (AD), in vivo and in vitro. Methods: For the AD in vivo experiment, 2,4-dinitrochlorobenzene (DNCB) induction and oral administration of PLG were performed on male BALB/c mice for four weeks. For in vitro experiments, keratinocytes were activated using TNF-α/IFN-γ in cultured human keratinocyte (HaCaT) cells. PLG inhibited inflammatory chemokine production and blocked the nuclear translocation of NF-κB p65 in activated keratinocytes. Results: As a result of oral administration of PLG, dermis and epidermis thickening, as well as eosinophil and mast cell infiltration, were attenuated in AD skin lesions. In addition, the levels of immunoglobulin E (IgE), pro-inflammatory cytokines, and the MAPK/NF-κB signaling pathway were decreased in serum and dorsal skin tissues. Furthermore, PLG inhibited inflammatory chemokine production and blocked the nuclear translocation of NF-κB p65 in activated keratinocytes. In addition, epigoitrin and adenosine, the standard compounds of PLG, were identified as candidate AD compounds. Conclusions: These results indicate that PLG is a potent therapeutic agent for attenuating symptoms of AD. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of rapamycin on the TNF-α-induced secretion of interleukin-6 (IL-6) and IL-8 in orbital fibroblasts and its possible mechanism. Materials and methods: Orbital fibroblasts were obtained from patients with thyroid-associated ophthalmopathy. IL-6 and IL-8 levels were measured by enzyme-linked immunosorbent assays. The down-regulation of PDCD4 was performed by PDCD4 siRNA transfection. Results: Rapamycin significantly enhanced TNF-α-induced IL-6 and IL-8 secretion from orbital fibroblasts. Down-regulation of PDCD4 by PDCD4 siRNA transfection reduced TNF-α-induced IL-6 and IL-8 secretion from orbital fibroblasts. In addition, TNF-α was found to promote the mTOR-dependent proteasome-mediated degradation of PDCD4. Rapamycin increased PDCD4 expression via the inhibition of TNF-α-induced PDCD4 degradation in orbital fibroblasts. Conclusion: Rapamycin enhances the TNF-α-induced secretion of IL-6 and IL-8 by suppressing PDCD4 degradation in orbital fibroblasts. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop an oral formulation that would improve the solubility and oral absorption of sirolimus using a TPGS micellar solution. The effect of TPGS on the solubility and stability of sirolimus was evaluated. The sirolimus-loaded TPGS micelles were prepared using the thin-film hydration method. The average size of the sirolimus-loaded TPGS micelles was 11 nm. The concentration of sirolimus in a 50 mg/mL TPGS micellar solution was 0.97 ± 0.12 mg/mL, which demonstrates an enhancement of approximately 400-fold from the solubility of sirolimus in water. Furthermore, pharmacokinetic studies in rats indicated that the TPGS micellar solution significantly improved the oral absorption of sirolimus. Therefore, the preliminary results from this study suggest that a TPGS micellar solution has great potential for clinical applications. [ABSTRACT FROM AUTHOR]