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Selaginella tamariscina is a perennial plant that is used for diverse diseases. This study investigated whether Selaginella tamariscina has an antiviral effect against influenza A virus (IAV) infection. We used green fluorescent protein (GFP)-tagged influenza A virus (IAV) to examine the effect of Selaginella tamariscina ethanol extract (STE) on influenza viral infection. Fluorescence microscopy and flow cytometry showed that STE potently represses GFP expression by the virus, dose-dependently. STE significantly inhibited the expression of the IAV M2, NP, HA, NA, NS1, and PB2 proteins. Time-of-addition and hemagglutination inhibition assays showed that STE has an inhibitory effect on hemagglutinin and viral binding on the cells at an early infection time. In addition, STE exerted a suppressive effect on the neuraminidase activity of the H1N1 and H3N2 IAVs. Furthermore, dose-dependently, STE inhibited the cytopathic effect induced by H3N2, as well as by H1N1 IAV. Especially in the presence of 200 µg/mL STE, the cytopathic effect was completely blocked. Our findings suggest that STE has antiviral efficacy against IAV infection; thus, it could be developed as a natural IAV inhibitor. [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]

Background: As breast augmentation has become more popular, an increasing number of women with augmented breasts require treatment for breast cancer. This study aimed to assess the outcomes of postoperative whole breast radiation therapy (WB-RT) in Asian patients with breast cancer who underwent prior cosmetic breast implantation. Methods: We retrospectively reviewed the medical records of 61 patients with breast cancer who had prior cosmetic breast implants (prior-CBI) and underwent breast-conserving surgery (BCS) and WB-RT between 2015 and 2020. The median implant volume was 238.8 cc, with a median interval of 84.7 months between the prior-CBI and BCS. WB-RT was administered with either conventional fractionation (CF-RT) at 50 Gy in 25 fractions (N = 36) or hypofractionation (HF-RT) at 42.6 Gy in 16 fractions (N = 25). The incidences of implant-related complications (IRC) and their contributing factors were analyzed. Results: After a median follow-up of 43.5 months, the 3-year cumulative incidences of IRC and implant loss were 17.2% and 4.9%, respectively. Among the four (6.6%) patients who opted for implant removal after RT, three were potentially related to RT-related capsular contracture. There was no difference in the 3-year cumulative IRC rates following CF-RT and HF-RT (12.2% and 26.7%, respectively; p = 0.120). The risk factors for IRC included a larger implant size (> 260 cc) and a higher ratio of breast tissue to implant volume. Conclusions: This study demonstrated a favorable safety profile of WB-RT for treatment of breast cancer in Asian women with prior-CBI. The integration of HF-RT following BCS was thought to be a feasible approach. [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]

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]

Purpose: This study aimed to compare the radiosensitizing effect of the PARP inhibitor, Olaparib, between proton and X-rays irradiations in BRCA-proficient breast cancer (BC) cells. Methods: Two BRCA-proficient BC cell lines, MDA-MB-231 and T47D BC, were used. Cell proliferation was assessed using the CCK-8 assay, and radiosensitivity was determined through the clonogenic survival assay. Flow cytometry was employed to analyze cell cycle distribution and apoptosis. The kinetics of DNA damage repair were evaluated using γH2AX immunofluorescence imaging and the comet assay. Tumor spheroid assays were conducted to test radiosensitivity in a three-dimensional culture condition. Results: Olaparib sensitized both MDA-MB-231 and T47D cells to proton and X-ray irradiation in the clonogenic assay. MDA-MB-231 cells exhibited a higher dose enhancement factor for Olaparib than T47D cells. Olaparib increased radiation-induced G2/M cell cycle arrest and apoptosis specifically in MDA-MB-231 cells. γH2AX immunostaining and the comet assay showed Olaparib augmented radiation-induced DNA damage and apoptosis. The enhancement effect of Olaparib was more pronounced in proton irradiation than in X-ray irradiation, particularly in MDA-MB-231 cells than T47D cells. Both radiation and Olaparib dose-dependently inhibited spheroid growth in both cell lines. The synergy scores demonstrated that Olaparib interacted more strongly with protons than X-rays. The addition of an ATR inhibitor further enhanced Olaparib-induced proton radiosensitization in MDA-MB-231 cells. Conclusion: This study found that Olaparib enhanced radiation efficacy in BRCA-proficient breast cancer cells, with a more pronounced effect observed with proton irradiation compared to X-ray irradiation. Combining Olaparib with an ATR inhibitor increased the radiosensitizing effect of protons. [ABSTRACT FROM AUTHOR]

Panax ginseng Meyer and Inula japonica Thunb. are well established in traditional medicine and are known for their therapeutic properties in managing a range of ailments such as diabetes, asthma, and cancer. Although P. ginseng and I. japonica can alleviate pulmonary fibrosis (PF), the anti-fibrosis effect on PF by the combination of two herbal medicines remains unexplored. Therefore, this study explores this combined effect. In conditions that were not cytotoxic, MRC-5 cells underwent treatment using the formula combining P. ginseng and I. japonica (ISE081), followed by stimulation with transforming growth factor (TGF)-β1, to explore the fibroblast-to-myofibroblast transition (FMT). After harvesting the cells, mRNA levels and protein expressions associated with inflammation and FMT-related markers were determined to evaluate the antiinflammation activities and antifibrosis effect of ISE081. Additionally, the anti-migratory effects of ISE081 were validated through a wound-healing assay. ISE081 remarkably reduced the mRNA levels of interleukin (IL)-6, IL-8, α-smooth muscle actin (SMA), and TGF-β1 in MRC-5 cells and suppressed the α-SMA and fibronectin expressions, respectively. Furthermore, ISE081 inhibited Smad2/3 phosphorylation and wound migration of MRC-5 cells. Under the same conditions, comparing those of ISE081, P. ginseng did not affect the expression of α-SMA, fibronectin, and Smad2/3 phosphorylation, whereas I. japonica significantly inhibited them but with cytotoxicity. The results indicate that the synergistic application of P. ginseng and I. japonica enhances the anti-fibrotic properties in pulmonary fibroblasts and concurrently diminishes toxicity. Therefore, ISE081 has the potential as a prevention and treatment herbal medicine for PF. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). Methods: Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. Results: The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887–1.069) and 0.866 (interquartile range: 0.773–0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = − 0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. Conclusion: Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry. [ABSTRACT FROM AUTHOR]

Background: Angiosarcoma is an extremely rare malignant tumor. So far, only about 42 cases of angiosarcoma involving the eyelids have been reported. Eyelid angiosarcoma occurs more frequently in elderly Caucasian males and is prone to misdiagnosis. We present a case report in a young Asian male patient with eyelid angiosarcoma that was misdiagnosed as a chalazion. Case presentation: A 46-year-old South Korean male with no underlying disease had a right lower lid mass. The lesion was initially misdiagnosed as a chalazion at a local clinic, but a diagnosis of eyelid angiosarcoma was made after the first biopsy trial. PET-CT was performed to ensure that there was no metastasis in the whole body. Surgical excision with enough surgical margin was used alone for treatment and reconstruction was performed with a tarsoconjunctival advancement flap (modified Hughes procedure), which helped ensure good cosmesis. No recurrence was observed 4 years and 5 months after the surgery. Conclusions: The current study presents the first case of chalazion-mimicked eyelid angiosarcoma in a young Asian male aged under 50 years. This case shows that even if a benign eyelid disease is suspected in a young patient, an incisional biopsy must be performed to confirm whether the lesion is malignant. Since the prognosis is good for the case of eyelid angiosarcoma, if there is no clear evidence of distal metastasis, surgical resection should be performed with an enough safety margin. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

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]

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]

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]

Broccoli (Brassica oleracea L. var. Italica) leaves are a byproduct of broccoli and could be used as a food source. The study aimed to evaluate the effect of broccoli leaves on influenza A virus (IAV) infection. We investigated the effect of ethanol extract of Broccoli leaves (EBL) on IAV infection using green fluorescent protein (GFP)–tagged Influenza A/PR/8/34 virus (PR8-GFP IAV). When EBL and PR8-GFP IAV were cotreated to RAW 264.7 cells, the fluorescence microscopy and fluorescence-activated cell sorting (FACS) analysis showed that EBL significantly reduced the levels of GFP expression by influenza viral infection dose-dependently. Immunofluorescence (IF) analysis confirmed that EBL decreased the expression of IAV proteins. EBL exhibited a strong inhibitory effect of IAV binding on the cells and moderate virucidal impact. Consistently, EBL potently suppressed the hemagglutination by IAV infection. These results indicate that EBL prevents IAV attachment via the inhibition of HA upon viral infection. Finally, EBL as an HA inhibitor of IAV could be used as the natural antiviral source to protect against influenza viral infection. [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 impact of immediate breast reconstruction (iBR) on patients treated with post-mastectomy radiation therapy (PMRT) using propensity score matching (PSM). Methods: After a retrospective review of patients treated with PMRT between 2008 and 2017, we included 153 patients who underwent iBR and 872 patients who did not undergo iBR. Among the 153 patients who underwent iBR, 34 received one-stage iBR with autologous tissue and 119 received two-stage iBR. Conventional fractionated PMRT with a total dose of 50–50.4 Gy in 25–28 fractions was performed in all patients. Propensity scores were calculated via logistic regression. Results: Patients who underwent iBR were younger, had early stage disease, and had more frequent hormone receptor-positive tumor than those who did not undergo iBR. After PSM, 127 patients from each group with well-balanced characteristics were selected. With a median follow-up of 67.5 months, iBR led to better 6-year disease-free survival rates compared to no iBR before PSM (84.8% vs. 71.4%, p = 0.003); after PSM, there was no significant difference (84.8% vs. 75.5%, p = 0.130). On multivariable analysis in the matched cohort, iBR was not associated with inferior disease-free survival (hazard ratio, 0.67; p = 0.175). In the sensitivity analysis, iBR was not associated with a lower disease-free survival across all prognostic groups. The 5-year cumulative incidence of iBR failure was 15.0%. Conclusion: In patients with adverse pathologic factors planning to receive PMRT, iBR did not compromise oncologic outcomes. In addition, iBR can be considered in patients treated with PMRT with several clinicopathologic risk factors. [ABSTRACT FROM AUTHOR]

Aim: This study was performed to evaluate patterns of breast cancer subtypes in Korean patients with synchronous (SBC) or metachronous bilateral breast cancer (MBC). Methods: We retrospectively reviewed records of 302 patients with SBC (n = 161) or MBC (n = 141) who received curative surgery at our hospital between 1995 and 2013. Expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was determined by immunohistochemistry (IHC) staining. We categorized breast cancers into the following subtypes: ER+ or PR+, HER2− (i.e., luminalA); ER+ or PR+, HER2+ (i.e., luminalB HER2+); ER−, PR− and HER2+ (i.e., HER2‐enriched); ER−, PR− and HER2− (i.e., triple negative, TN). Results: More patients with MBC were ≤40 years at the time of breast cancer diagnosis than patients with SBC (34.6% vs. 19.3%, P < 0.01). The proportion of subtypes in SBC and MBC were as follows: luminalA, 65.8% vs. 45.0%; luminalB, HER2+, 9.0% vs. 8.5%; HER2‐enriched, 4.1% vs. 12.1%; and TN, 11.2% vs. 31.2%, respectively (P < 0.01). The 10‐year overall survival rate in patients with SBC and MBC was 89.0% and 93.6%, respectively. The 10‐year disease‐free survival rate in patients with SBC and MBC was 79.6% and 80.9%, respectively. Locoregional recurrence was found in 2.5% of patients with SBC and 9.9% of patients with MBC. Distant metastasis occurred in 8.7% of patients with SBC and 4.9% of patients with MBC. Conclusion: The distribution of breast cancer subtypes was different between SBC and MBC. TN‐subtype was profoundly more frequent in MBC whereas luminal‐subtype was most frequently found among SBC. [ABSTRACT FROM AUTHOR]

Background: Ocular hypertension is a major risk factor for glaucoma, which is characterized by the presence of ganglion cells, ganglion disease, and an irreversible reduction in the number of ganglion cells and axons. Although the anti-inflammatory and detoxifying effects of the maple tree (Acer palmatum Thunb.) leave extract are well known, it is unclear whether the extract can protect the eyes from ocular hypertension. Objective: This study was conducted to investigate whether the alcohol extract from A. palmatum Thunb. leaves (KIOM-2015E) had a protective effect on eyes in an animal model of steroid-induced ocular hypertension. We investigated whether KIOM-2015E had a therapeutic effect on ocular diseases induced by elevated intraocular pressure (IOP) by reducing IOP. Results: Ocular hypertension was induced in 9-week-old female C57BL/6 mice weighing 23–27 g with 4 weeks of steroid injection. After 4 weeks, 1 or 2 mg/mL of KIOM-2015E was instilled in the mice three times a day for 5 weeks. IOP was measured weekly, and the eyes were lysed after drug administration to investigate the changes in the histological parameters and the levels of anti-apoptotic proteins. IOP was elevated, OPN1SW levels were decreased in the retinal tissue, and GFAP levels were increased in the mice with induced ocular hypertension. IOP was lowered in a concentration-dependent manner in the mice treated with KIOM-2015E. KIOM-2015E was confirmed to have an inhibitory effect on the histological changes on the retina, activity of glial and astrocytic cells, and cell death. Conclusions: Treatment with KIOM-2015E improved steroid-induced ocular hypertension. KIOM-2015E prevented retinal degeneration caused by increased ocular pressure by regulating protein levels and histological parameter expression in retina. [ABSTRACT FROM AUTHOR]

Propose: We aimed to investigate the prevalence and risk factors of dry eye syndrome (DES) among a population-based cohort study.Methods: This cross-sectional study was conducted on 475 subjects (184 men and 291 women) enrolled in the Study Group for Environmental Eye Disease at July 2013. Using the ocular surface disease index (OSDI), we measured the DES severity and defined DES as OSDI score ≥13. Current symptoms of DES and possible risk factors such as body mass index, occupations, comorbidities, exercise, smoking and drinking status were assessed by multivariate logistic regression.Results: Prevalence of DES was significantly higher in women (52.6%) than in men (41.9%) (p <.001). Compared to white-collar workers, blue-collar workers and unemployed persons showed significantly higher DES prevalence and severity. Compared to those with low BMI (<23.0 kg/m2), people with extremely high BMI (≥30.0 kg/m2) had significantly higher odds ratio (OR) of having DES after fully adjusted for sex, age, hypertension, diabetes, menopausal status, hormone replacement therapy, occupation, and lifestyle factors (OR: 2.83, 95% confidence interval: 1.04–7.71).Conclusions: We found some novel factors which have been unknown to the relationship with DES through the five years observation of the cohort. The positive associations of unemployment status, blue-collar work, alcohol habit, and obesity with DES suggests a person's comprehensive condition, not individual factors, contribute significantly in developing DES. Further studies will be helpful to understand the underlying mechanisms. [ABSTRACT FROM AUTHOR]

One strategy for a functional cure of HIV-1 is "block and lock", which seeks to permanently suppress the rebound of quiescent HIV-1 by epigenetic silencing. For the bivalent promoter in the HIV LTR, both histone 3 lysine 27 tri-methylation (H3K27me3) and DNA methylation are associated with viral suppression, while H3K4 tri-methylation (H3K4me3) is correlated with viral expression. However, H3K27me3 is readily reversed upon activation of T-cells through the T-cell receptor. In an attempt to suppress latent HIV-1 in a stable fashion, we knocked down the expression or inhibited the activity of UTX/KDM6A, the major H3K27 demethylase, and investigated its impact on latent HIV-1 reactivation in T cells. Inhibition of UTX dramatically enhanced H3K27me3 levels at the HIV LTR and were associated with increased DNA methylation. In latently infected cells from patients, GSK-J4, which is a potent dual inhibitor of the H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A, effectively suppressed the reactivation of latent HIV-1 and also induced DNA methylation at specific sites in the 5'LTR of latent HIV-1 by the enhanced recruitment of DNMT3A to HIV-1. Nonetheless, suppression of HIV-1 through epigenetic silencing required the continued treatment with GSK-J4 and was rapidly reversed after removal of the drug. DNA methylation was also rapidly lost after removal of drug, suggesting active and rapid DNA-demethylation of the HIV LTR. Thus, induction of epigenetic silencing by histone and DNA methylation appears to be insufficient to permanently silence HIV-1 proviral transcription. Author summary: The "block and lock" strategy for a functional HIV-1 cure is based on the premise that permanent inactivation of the HIV-1 can be achieved by epigenetic silencing of the proviral DNA. For cellular genes, long-term silencing is achieved during cell differentiation by the induction of specific epigenetic modifications involving histone and DNA methylation. During HIV-1 silencing, histone methylation and DNA methylation are observed, but both sets of modifications can be reversed upon activation of T-cells through the T-cell receptor or potent latency reversing agents. In an attempt to enhance silencing of HIV-1 transcription, we used an inhibitor of H3K27 demethylases to increase H3K27 methylation. This in turn led to enhanced DNA methylation of HIV-1. Unfortunately, although the treatment effectively silenced HIV-1 and prevented viral reactivation, the silencing effects were short-lived and quickly reversed after removal of the drug. [ABSTRACT FROM AUTHOR]

Background: Excessive skeletal muscle loss during neoadjuvant concurrent chemoradiotherapy (NACRT) is significantly related to survival outcomes of oesophageal cancer. However, the conventional method for measuring skeletal muscle mass requires computed tomography (CT) images, and the calculation process is labour‐intensive. In this study, we built machine‐learning models to predict excessive skeletal muscle loss, using only body mass index data and blood laboratory test results. Methods: We randomly split the data of 232 male patients treated with NACRT for oesophageal cancer into the training (70%) and test (30%) sets for 1000 iterations. The naive random over sampling method was applied to each training set to adjust for class imbalance, and we used seven different machine‐learning algorithms to predict excessive skeletal muscle loss. We used five input variables, namely, relative change percentage in body mass index, albumin, prognostic nutritional index, neutrophil‐to‐lymphocyte ratio, and platelet‐to‐lymphocyte ratio over 50 days. According to our previous study results, which used the maximal χ2 method, 10.0% decrease of skeletal muscle index over 50 days was determined as the cut‐off value to define the excessive skeletal muscle loss. Results: The five input variables were significantly different between the excessive and the non‐excessive muscle loss group (all P < 0.001). None of the clinicopathologic variables differed significantly between the two groups. The ensemble model of logistic regression and support vector classifier showed the highest area under the curve value among all the other models [area under the curve = 0.808, 95% confidence interval (CI): 0.708–0.894]. The sensitivity and specificity of the ensemble model were 73.7% (95% CI: 52.6%–89.5%) and 74.5% (95% CI: 62.7%–86.3%), respectively. Conclusions: Machine learning model using the ensemble of logistic regression and support vector classifier most effectively predicted the excessive muscle loss following NACRT in patients with oesophageal cancer. This model can easily screen the patients with excessive muscle loss who need an active intervention or timely care following NACRT. [ABSTRACT FROM AUTHOR]

Background: This study was performed to evaluate circulating tumor DNA (ctDNA) kinetics during postoperative radiotherapy (PORT) in patients with residual triple-negative breast cancer (TNBC) at surgery following neoadjuvant chemotherapy (NAC). Methods: Stage II/III patients with post-NAC residual TNBC who required PORT were prospectively included in this study between March 2019 and July 2020. For 11 TNBC patients, next-generation sequencing targeting 38 genes was conducted in 55 samples, including tumor tissue, three plasma samples, and leukocytes from each patient. The plasma samples were collected at three-time points; pre-PORT (T0), after 3 weeks of PORT (T1), and 1 month after PORT (T2). Serial changes in ctDNA variant allele frequency (VAF) were analyzed. Results: Somatic variants were found in the tumor specimens in 9 out of 11 (81.8%) patients. Mutated genes included TP53 (n = 7); PIK3CA (n = 2); and AKT1, APC, CSMD3, MYC, PTEN, and RB1 (n = 1). These tumor mutations were not found in plasma samples. Plasma ctDNA variants were detected in three (27.3%) patients at T0. Mutations in EGFR (n = 1), CTNNB1 (n = 1), and MAP2K (n = 1) was identified with ctDNA analysis. In two (18.2%) patients, the ctDNA VAF decreased through T1 and T2 while increasing at T2 in one (9.1%) patient. After a median follow-up of 22 months, no patient showed cancer recurrence. Conclusion: Among patients with post-NAC residual TNBC, more than a quarter exhibited a detectable amount of ctDNA after curative surgery. The ctDNA VAF changed variably during the course of PORT. Therefore, ctDNA kinetics can serve as a biomarker for optimizing adjuvant treatment. [ABSTRACT FROM AUTHOR]

Background: There has been few research on how to measure skin status quantitatively throughout the course of radiotherapy (RT). We evaluated the changes in the skin induced by 2 different RT techniques using objective measurements in breast cancer patients. Methods: In this prospective study, between August 2015 and March 2019, serial measurements of the dermatological factors during and after postmastectomy radiotherapy (PMRT) were made in 40 breast cancer patients. PMRT was performed using the conventional photon tangential technique (PTT) or patient-tailored bolus technique (PTB). We analyzed these measurements using a mixed effect model and compared the clinically evaluated radiation dermatitis and patient-reported outcomes (PROs). Results: The trend of changes in melanin and erythema was significantly different between the PTB and PTT groups (p = 0.045 and 0.016, respectively). At the 3-month follow-up erythema intensity and melanin were higher in the PTB group than in PTT group (both p < 0.001). Eight patients (40% in the PTB group) reported grade 2 radiation dermatitis and 1 patient (5% in the PTB group) reported grade 3 radiation dermatitis. No grade 2 or higher radiation dermatitis was found in the PTT group. Ten patients (50%) in the PTB group and 3 patients (15%) in the PTT group reported severe erythema likely due to questionable clinical evaluation, but hyperpigmentation was rarely reported at the follow-up visits. Conclusion: The PTB group showed higher intensity of erythema at the end of RT than the PTT group and the increase in melanin lasted until the 3-month follow-up visits in the PTB group. Moreover, patients subjectively appealed more severe symptoms following PTB in PROs. [ABSTRACT FROM AUTHOR]

Background: It is difficult to assess the impact of multiple comorbidities on clinical outcomes in chronic obstructive pulmonary disease (COPD). In this study, we aimed to investigate exacerbation-associated comorbidities, determine whether the number of comorbidities is an independent risk factor for exacerbation, and identify other exacerbation-associated factors in a Korean COPD population using a nationwide population-based cohort. This study focused on severe exacerbations that required hospitalisation or emergency room visits.Methods: The National Health Insurance Service-National Sample Cohort, version 2.0, data sampled between 2002 and 2015 were analysed. Data from two years after the diagnosis of COPD were analysed for each participant (N = 12,554, entire cohort). Moreover, 42% of the participants underwent additional health examinations (N = 5306, health-screening cohort). Fifteen comorbidities that were previously reported as risk factors for exacerbations were examined. A logistic regression model was used to analyse association with exacerbations.Results: Asthma (1.57 [1.39-1.76] and 1.24 [1.06-1.44]), lung cancer (1.84 [1.30-2.59] and 2.28 [1.54-3.37]), and heart failure (1.39 [1.16-1.67] and 1.52 [1.18-1.97]) were associated with exacerbation in both cohorts (odds ratio [95% confidence interval] in the entire cohort and health-screening cohort, respectively). The number of comorbidities was an independent risk factor, and old age, male sex, low body mass index, and current smoking were also independent risk factors. High cholesterol levels and body mass index exerted protective effects against exacerbation.Conclusions: The number of comorbidities, certain comorbidities such as asthma, lung cancer and heart failure, and low BMI were associated with an increased risk of severe exacerbation in COPD patients. [ABSTRACT FROM AUTHOR]

Background: The effects of comorbidities on chronic obstructive pulmonary disease (COPD) have been usually studied individually in the past. In this study, we aimed to investigate the comorbidities associated with mortality, the effect of multimorbidity on mortality and other factors associated with mortality among Korean COPD population.Methods: The Korean National Health Insurance Service-National Sample Cohort version 2.0, collected between 2002 and 2015, was used. Among COPD patients [entire cohort (EC), N = 12,779], 44% of the participants underwent additional health examination, and they were analysed separately [health-screening cohort (HSC), N = 5624]. Fifteen comorbidities previously reported as risk factors for mortality were studied using Cox proportional hazards regression models.Results: Total mortality rates were 38.6 per 1000 person-years (95% CI 37.32-40.01) and 27.4 per 1000 person-years (95% CI 25.68-29.22) in EC and HSC, respectively. The most common causes of death were disease progression, lung cancer, and pneumonia. Only some of the comorbidities had a direct impact on mortality. Multimorbidity, assessed by the number of comorbid diseases, was an independent risk factor of all-cause mortality in both cohorts and was a risk factor of respiratory mortality only in HSC. The Kaplan-Meier analysis showed significant differences in survival trajectories according to the number of comorbidities in all-cause mortality but not in respiratory mortality. Low BMI, old age and male sex were independent risk factors for both mortalities in both cohorts.Conclusions: The number of comorbidities might be an independent risk factor of COPD mortality. Multimorbidity contributes to all-cause mortality in COPD, but the effect of multimorbidity is less evident on respiratory mortality. [ABSTRACT FROM AUTHOR]

Case Presentation: A 21-year-old man was admitted to our hospital with recurrent bilateral pneumothorax and hemoptysis. Three years earlier, he underwent coil embolization due to a subarachnoid hemorrhage caused by an intracerebral aneurysm rupture. Two months after the coil embolization, he underwent an emergent total colectomy due to a massive infarction of the colon. One year after the colectomy, he started to have recurrent hemoptysis, and a few months later, multiple episodes of bilateral pneumothorax that required a chest tube placement began to occur. Notably, he had a history of easy bruising. He was taking Depakote and aspirin to prevent seizure and thromboembolic complications, respectively, both of which he began taking after the coil embolization. He denied the use of any illicit drugs. The histories of his parents and sister were not remarkable. [ABSTRACT FROM AUTHOR]

The postoperative hypofractionated intensity-modulated radiation therapy (POHIM-RT) trial is a phase II study to evaluate toxicity following hypofractionated intensity modulated radiation therapy (IMRT) for cervical cancer. This study describes the results of a benchmark procedure for RT quality assurance of the POHIM-RT trial. Six participating institutions were provided computed tomography for RT planning and an IMRT plan for a sample and were instructed to delineate volumes, create a treatment plan and quality assurance (QA) plan, and submit the results of all procedures. The inter-institutional agreements on RT volume and plan results were evaluated using the kappa value and dice similarity coefficients. The simultaneous truth and performance level estimation (STAPLE) method was employed to generate a consensus target volume. The treatment volumes, organs-at-risk volumes, and results of the RT plan and QA reported by the institutions were acceptable and adhered well to the protocol. In terms of clinical target volume (CTV) delineation, there were differences between the institutions, particularly in vaginal cuff and paracolpium subsites. Consensus CTV was generated from the collected CTVs with the STAPLE method. The participating institutions showed considerable agreement regarding volume, dose and QA results. To improve CTV agreement in CTV, we provided feedback with images of the consensus target volume and detailed written guidelines for specific subsites that were the most heterogeneous. [ABSTRACT FROM AUTHOR]

This study was performed to identify risk factors for pelvic nodal failure (PNF) after definitive concurrent chemo-radiotherapy (CCRT) in patients with metastatic pelvic lymph nodes (mPLNs) from squamous cell carcinoma (SCC) of the cervix. We retrospectively reviewed data on 80 patients who received definitive CCRT between 2005 and 2014 at our hospital. All patients underwent brachytherapy and whole-pelvic radiotherapy (WPRT) without nodal boost. mPLNs was diagnosed by magnetic resonance imaging and positron emission tomography. The rate of PNF and factors affecting PNF were analysed. A total of 156 mPLNs were found. The median number of mPLNs was 2 per patient (range 1–6); the median short diameter was 1.7 cm (range 1.0–4.2 cm). After a median follow-up of 64 months, 10 (6.4%) mPLNs failed in 13 (16.3%) patients. The 5-year PNF-free survival (PNFFS), disease-free survival and overall survival rates were 83.4, 62.7 and 74.7%, respectively. The mPLN size was not associated with the risk of PNF. However, pre-radiotherapy SCC antigen (SCC-Ag) >6.8 ng/mL and number of mPLNs >2 were significant risk factors for PNF. Using the two risk factors, we categorized the patients into three risk groups. The 5-year PNFFS rates in patients with 0, 1 and 2 risk factors were 100.0, 78.3 and 44.4%, respectively (P  < 0.01). SCC-Ag level and number of mPLNs were significant factors for PNF. Patients with both risk factors developed frequent PNF after WPRT without nodal boost. The two risk factors can be a guide in deciding whether to administer nodal boost radiotherapy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the optimal radiotherapy (RT) regimen for patients with clinical metastasis to the internal mammary lymph node (cIMN+) from breast cancer.Methods: We retrospectively reviewed the medical records of 84 patients with cIMN+ breast cancer treated with curative surgery, taxane-based chemotherapy, and postoperative RT between January 2009 and December 2014. Postoperative RT was administered to the whole breast or chest wall using 50 Gy in 2 Gy fractions. Boost RT to the internal mammary lymph node (IMN) was administered at the physician's discretion. We categorized patients into two groups according to the IMN dose as follows: low-dose IMN RT (50.0-63.5 Gy) and high-dose IMN RT (63.6-70.4 Gy).Results: After a median follow-up of 58 months (range, 12-111 months), IMN recurrence was observed in 2 patients (2.4%), and all IMN recurrences developed simultaneously with distant metastases. The 5-year locoregional recurrence-free survival, disease-free survival (DFS), and overall survival rates were 89.1, 72.0, and 81.2%, respectively. The triple-negative subtype, IMN size ≥1.0 cm, old age, and low-dose IMN were significantly associated with poor DFS. Among the patients with IMN size ≥1.0 cm, the 5-year DFS was significantly higher in those treated with high-dose IMN RT than in those treated with low-dose IMN RT (69.3% vs. 33.3%, p = 0.019).Conclusions: IMN RT without IMN dissection resulted in favorable outcomes in cIMN+ breast cancer. For patients with a large IMN, a higher IMN radiation dose might be needed for disease control. [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]

Aloe vera ethanol extract (AVE) reportedly has significant anti-influenza virus activity, but its underlying mechanisms of action and constituents have not yet been completely elucidated. Previously, we have confirmed that AVE treatment significantly reduces the viral replication of green fluorescent protein-labeled influenza A virus in Madin-Darby canine kidney (MDCK) cells. In addition, post-treatment with AVE inhibited viral matrix protein 1 (M1), matrix protein 2 (M2), and hemagglutinin (HA) mRNA synthesis and viral protein (M1, M2, and HA) expressions. In this study, we demonstrated that AVE inhibited autophagy induced by influenza A virus in MDCK cells and also identified quercetin, catechin hydrate, and kaempferol as the active antiviral components of AVE. We also found that post-treatment with quercetin, catechin hydrate, and kaempferol markedly inhibited M2 viral mRNA synthesis and M2 protein expression. A docking simulation suggested that the binding affinity of quercetin, catechin hydrate, and kaempferol for the M2 protein may be higher than that of known M2 protein inhibitors. Thus, the inhibition of autophagy induced by influenza virus may explain the antiviral activity of AVE against H1N1 or H3N2. Aloe vera extract and its constituents may, therefore, be potentially useful for the development of anti-influenza agents. [ABSTRACT FROM AUTHOR]

We compared treatment outcomes between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy alone with R-CHOP followed by consolidative radiation therapy (RT) in diffuse large B-cell lymphoma (DLBCL). We analyzed 404 patients with Stage I–II DLBCL who received six to eight cycles of R-CHOP and achieved a good response after a full course of chemotherapy. Propensity-score matching was used to assess the role of consolidative RT. The R-CHOP alone group (n = 184) was matched in a 1:2 ratio with the R-CHOP plus RT group (n = 92). Twenty-four (13.0%) of 184 patients receiving R-CHOP alone and 8 (8.7%) of 92 patients receiving R-CHOP plus RT had bulky diseases (>7.5 cm). A Deauville score of 1–2 was achieved for 159 (86.4%) of 184 patients receiving R-CHOP alone and 84 (91.3%) of 92 patients receiving R-CHOP plus RT. After a median follow-up time of 42 months, the recurrence-free survival (RFS) rate (86.7% vs 93.0%, P = 0.464) and overall survival rate (88.3% vs 95.1%, P = 0.295) at 5 years did not differ significantly between the R-CHOP alone and R-CHOP plus RT arms. In the additional multivariate analyses, large tumor size (>7.5 cm) was significantly associated with decreased RFS (hazard ratio, 2.368 and confidence interval, 1.837–6.697; P = 0.048). Consolidative radiation was not a significant factor for RFS (P = 0.563). Tumor size was a significant factor for RFS in the rituximab era. The outcome of omitting consolidative RT for good responders after six to eight cycles of R-CHOP chemotherapy was acceptable in early-stage DLBCL without a bulky disease. [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]

The aim of this study was to assess the anti-inflammatory and anti-apoptotic effects of KIOM-2015EW, the hot-water extract of maple leaves in hyperosmolar stress (HOS)-induced human corneal epithelial cells (HCECs). HCECs were exposed to hyperosmolar medium and exposed to KIOM-2015EW with or without the hyperosmolar media. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 production and apoptosis were observed, and the activation of mitogen-activated protein kinases (MAPKs) including extracellular signal regulated kinase (ERK), p38 and c-JUN N-terminal kinase (JNK) signaling and nuclear factor (NF)-κB was confirmed. Compared to isomolar medium, the induction of cell cytotoxicity significantly increased in HCECs exposed to hyperosmolar medium in a time-dependent manner. KIOM-2015EW-treatment significantly reduced the mRNA and protein expression of pro-inflammatory mediators and apoptosis. KIOM-2015EW-treatment inhibited HOS-induced MAPK signaling activation. Additionally, the HOS-induced increase in NF-κB phosphorylation was attenuated by KIOM-2015EW. The results demonstrated that KIOM-2015EW protects the ocular surface by suppressing inflammation in dry eye disease, and suggest that KIOM-2015EW may be used to treat several ocular surface diseases where inflammation plays a key role. [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]

Coptidis Rhizoma is derived from the dried rhizome of Ranunculaceous plants and is a commonly used traditional Chinese medicine. Although Coptidis Rhizoma is commonly used for its many therapeutic effects, antiviral activity against respiratory syncytial virus (RSV) has not been reported in detail. In this study, we evaluated the antiviral activities of Coptidis Rhizoma extract (CRE) against RSV in human respiratory tract cell line (HEp2) and BALB/c mice. An effective dose of CRE significantly reduces the replication of RSV in HEp2 cells and reduces the RSV-induced cell death. This antiviral activity against RSV was through the induction of type I interferon-related signaling and the antiviral state in HEp2 cells. More importantly, oral administration of CRE exhibited prophylactic effects in BALB/c mice against RSV. In HPLC analysis, we found the presence of several compounds in the aqueous fraction and among them; we confirmed that palmatine was related to the antiviral properties and immunemodulation effect. Taken together, an extract of Coptidis Rhizoma and its components play roles as immunomodulators and could be a potential source as promising natural antivirals that can confer protection to RSV. These outcomes should encourage further allied studies in other natural products. [ABSTRACT FROM AUTHOR]