Self-powered semitransparent WS2/LaVO3vertical-heterostructure photodetectors by employing interfacial hexagonal boron nitride.

Two-dimensional (2D) semiconductor and LaVO3materials with high absorption coefficients in the visible light region are attractive structures for high-performance photodetector (PD) applications. Insulating 2D hexagonal boron nitride (h-BN) with a large band gap and excellent transmittance is a very attractive material as an interface between 2D/semiconductor heterostructures. We first introduce WS2/h-BN/LaVO3semitransparent PD. The photo-current/dark current ratio of the device exhibits a delta-function characteristic of 4 × 105at 0 V, meaning 'self-powered'. The WS2/h-BN/LaVO3PD shows up to 0.27 A W-1responsivity (R) and 4.6 × 1010cm Hz1/2W-1detectivity (D*) at 730 nm. Especially, it was confirmed that theD* performance improved by about 5 times compared to the WS2/LaVO3device at zero bias. Additionally, it is suggested that the PD maintains 87% of its initialRfor 2000 h under the atmosphere with a temperature of 25 °C and humidity of 30%. Based on the above results, we suggest that the WS2/h-BN/LaVO3heterojunction is promising as a self-powered optoelectronic device.

Fermented Aronia melanocarpa Inhibits Melanogenesis through Dual Mechanisms of the PI3K/AKT/GSK-3ß and PKA/CREB Pathways.

UV light causes excessive oxidative stress and abnormal melanin synthesis, which results in skin hyperpigmentation disorders such as freckles, sunspots, and age spots. Much research has been carried out to discover natural plants for ameliorating these disorders. Aronia melanocarpa contains various polyphenolic compounds with antioxidative activities, but its effects on melanogenesis have not been fully elucidated. In this study, we investigated the inhibitory effect of fermented Aronia melanocarpa (FA) fermented with Monascus purpureus on melanogenesis and its underlying mechanism in the B16F10 melanoma cell line. Our results indicate that FA inhibited tyrosinase activity and melanogenesis in alpha-melanocyte-stimulating hormone (α-MSH)-induced B16F10 cells. FA significantly downregulated the PKA/CREB pathway, resulting in decreased protein levels of tyrosinase, TRP-1, and MITF. FA also inhibited the transcription of MITF by increasing the phosphorylation levels of both GSK3ß and AKT. Interestingly, we demonstrated that these results were owing to the significant increase in gallic acid, a phenolic compound of Aronia melanocarpa produced after the fermentation of Monascus purpureus. Taken together, our research suggests that Aronia melanocarpa fermented with Monascus purpureus acts as a melanin inhibitor and can be used as a potential cosmetic or therapeutic for improving hyperpigmentation disorders.

The Anti-Inflammatory Activities of Fermented Curcuma That Contains Butyrate Mitigate DSS-Induced Colitis in Mice.

Inflammatory bowel disease is characterized by a radical imbalance of inflammatory signaling pathways in the gastrointestinal tract, and it is categorized into two diseases, such as Crohn's disease and ulcerative colitis. In this study, we investigated anti-inflammatory activities using fermented Curcuma that contains butyrate (FB). Nitric oxide production in RAW 264.7 cells and the expression of inducible nitric oxide synthase in the intestinal mucosa appears to be enhanced in active ulcerative colitis. Here, the cytotoxicity, physiological activity, and anti-inflammatory efficacy of FB in colitis animals were investigated. To verify the anti-inflammatory effect, this study was conducted using the dextran sulfate sodium (DSS)-induced colitis mice model. As a result, non-toxicity was confirmed, and anti-inflammatory effects were revealed by inducing a reduction of LPS-induced NO production. In the DSS-induced colitis, reduced weight was recovered and a decrease in inflammatory factors Ig-E and TNF-α in the mesenteric lymph node (MLN) and spleen was induced, and it was confirmed to help with the morphological remodeling of the intestine. In conclusion, this paper suggests that FB can help to alleviate intestinal inflammation and to improve the intestinal environment, with the help of morphological remodeling.

Application of electrical treatment on Euglena gracilis for increasing paramylon production.

Paramylon also called ß-1,3-glucan is a value-added product produced from Euglena gracilis. Recently, researchers have developed various strategies for the enhanced paramylon production, among which electrical treatment for microbial stimulation can be an alternative owing to the applicability to large-scale cultivation. In this study, we applied the electrical treatment for enhanced paramylon production and found the proper treatment conditions. Under the treatment with platinum electrodes at 10 mA, the paramylon production of treated cells was significantly increased about 2.5-fold, compared to those of the untreated cells, although the density of cells was maintained due to considerable stress. The size of treated cells became larger, possibly due to the increased level of paramylon production within the cells. Accordingly, the contents of glucose uptake, glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), and uridine diphosphoglucose (UDPG) were shifted to appropriate states for the process of paramylon synthesis under the treatment. The increased level of transcripts encoding glucan synthase-like 2 (EgGSL2) was also confirmed via droplet digital PCR (ddPCR) under the treatment. Overall, this study makes a major contribution to research on electrical stimulation and provides new insights into E. gracilis metabolism like paramylon synthesis. KEY POINTS: • Electrical treatment induced the paramylon production and morphological change of Euglena gracilis. • The glucose uptake of E. gracilis was increased during the electrical treatment, fueling the paramylon synthesis.

A strategic approach to apply bacterial substances for increasing metabolite productions of Euglena gracilis in the bioreactor.

Bacterial extracellular polymeric substances (EPS) are promising materials that have a role in enhancing growth, metabolite production, and harvesting efficiency. However, the validity of the EPS effectiveness in scale-up cultivation of microalgae is still unknown. Therefore, in order to verify whether the bacterial metabolites work in the scale-up fermentation of microalgae, we conducted a bioreactor fermentation following the addition of bacterial EPS derived from the marine bacterium, Pseudoalteromonas sp., to Euglena gracilis. Various culture strategies (i.e., batch, glucose fed-batch, and glucose and EPS fed-batch) were conducted to maximize metabolite production of E. gracilis in scale-up cultivation. Consequently, biomass and paramylon concentrations in the continuous glucose and EPS-treated culture were enhanced by 3.0-fold and 4.2-fold (36.1 ± 1.4 g L-1 and 25.6 ± 0.1 g L-1), respectively, compared to the non-treated control (12.0 ± 0.3 g L-1 and 6.1 ± 0.1 g L-1). Also, the supplementation led to the enhanced concentrations of α-tocopherols and total fatty acids by 3.7-fold and 2.8-fold, respectively. The harvesting efficiency was enhanced in EPS-supplemented cultivation due to the flocculation of E. gracilis. To the best of our knowledge, this is the first study that verifies the effect of bacterial EPS in scale-up cultivation of microalgae. Also, our results showed the highest paramylon productivity than any other previous reports. The results obtained in this study showed that the scale-up cultivation of E. gracilis using bacterial EPS has the potential to be used as a platform to guide further increases in scale and in the industrial environment. KEY POINTS: Effect of EPS on Euglena gracilis fermentation was tested in bioreactor scale. EPS supplement was effective for the paramylon, α-tocopherol, and lipid production. EPS supplement induced the flocculation of E. gracilis.

Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response.

BACKGROUND: Oropharyngeal cancer (OPC) exhibits diverse immunological properties; however, their implications for immunotherapy are unknown. METHODS: We analysed 37 surgically resected and nine recurrent or metastatic anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-treated OPC tumours. OPCs were classified into immune-rich (IR), mesenchymal (MS) and xenobiotic (XB) subtypes based on RNA-sequencing data. RESULTS: All IR type tumours were human papillomavirus (HPV) positive, most XB types were HPV negative, and MS types showed mixed HPV status. The IR type showed an enriched T cell exhaustion signature with PD-1+ CD8+ T cells and type I macrophages infiltrating the tumour nest on multiplex immunohistochemistry. The MS type showed an exclusion of CD8+ T cells from the tumour nest and high MS and tumour growth factor-ß signatures. The XB type showed scant CD8+ T cell infiltration and focal CD73 expression. The IR type was associated with a favourable response signature during anti-PD-1/PD-L1 therapy and showed a high APOBEC mutation signature, whereas the MS and XB types showed resistance signature upregulation. Among anti-PD-1/PD-L1-treated OPC patients, the IR type showed a favourable clinical response (3/4 patients), whereas the XB type showed early progression (3/3 patients). CONCLUSION: Our analysis classified OPCs into three subtypes with distinct immune microenvironments that are potentially related to the response to anti-PD-1/PD-L1 therapy.

Correction: Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Comparison of Surgical Outcomes of Robotic and Conventional Approaches in Patients with Pre- and Poststyloid Parapharyngeal Space Tumors.

BACKGROUND: Benefits and drawbacks of robotic surgical approaches for parapharyngeal space (PPS) tumors remain undetermined. The purpose of this study is to compare surgical outcomes of PPS tumor patients who underwent robotic surgery with those of patients who received conventional surgical treatment. PATIENTS AND METHODS: We retrospectively analyzed clinicopathologic data from 136 patients who underwent surgical removal of PPS tumors via conventional or robotic approaches. RESULTS: We identified PPS tumors in pre- and poststyloid regions in 87 (64%) and 49 (36%) patients, respectively. There were 48 (35.3%) pleomorphic adenomas, 36 (26.5%) schwannomas, and 24 (17.6%) paragangliomas. Conventional surgical techniques were performed in 83 patients, and robotic surgical approaches were administered to 53 patients. Transcervical-parotid and transcervical approaches were most commonly performed in conventional surgery, while transoral and retroauricular approaches were the preferred surgical methods in robotic surgery for pre- and poststyloid PPS tumors, respectively. Robotic surgery resulted in less estimated blood loss during poststyloid PPS tumor surgery. Postoperative cranial nerve complications were noted in 36 of 83 cases (43.4%) in the conventional surgery group and in 17 of 53 cases (32.1%) in the robotic surgery group. Intraoperative tumor spillage of pleomorphic adenoma showed no significant differences between the two groups (13.6% in conventional vs. 15.4% in robotic surgery). The mean follow-up time was 4.9 ± 3.4 years, and recurrences were observed in two patients during follow-up without a significant difference between the two groups (4.5% in conventional vs. 3.8% in robotic surgery). CONCLUSIONS: Robotic surgery in PPS tumors is feasible through transoral, retroauricular, or combined approaches and provides treatment outcomes comparable to those of conventional open surgery.

Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer.

BACKGROUND: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. METHODS: Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform. RESULTS: From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR, CCND1, MYC, and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56], P < 0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53], P < 0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor. CONCLUSIONS: Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.

Four-week repeated dose oral toxicity study of KDS2010, a novel selective monoamine oxidase B inhibitor, in Sprague Dawley rats.

Repeated dose oral toxicity and toxicokinetic of KDS2010, a new drug for Parkinson's disease, was investigated after 4-week repeated oral administration at 30, 50, 75, or 100 mg/kg/day in rats. Body weight and body weight gain decreased in rats of both sexes in the 75 and 100 mg/kg groups, and food consumption was reduced in male rats of the 75 and 100 mg/kg male groups. Histological alterations were observed in the kidney (urothelial hyperplasia, inflammatory cell infiltration in the renal pelvis, tubular vacuolation/degeneration, basophilic tubules, and hyaline droplets in the proximal tubules) of the 75 and 100 mg/kg male groups and the 50 and 100 mg/kg female groups. The 75 and 100 mg/kg male groups showed adverse effect in the testes (degeneration/exfoliation of germ cells, seminiferous tubules atrophy) and epididymis (cellular debris, oligospermia). These changes were partially recovered after a 2-week recovery period. However, basophilic tubules and hyaline droplets in the proximal tubules in the kidney and germ cell degeneration/exfoliation in the testis were not recovered. In toxicokinetics study, systemic exposure to KDS2010 increased proportionally in both sexes by in a dose -dependent manner. In addition, repeated administration for 4 weeks led to increased tendency of systemic exposure in both sexes compared with that in Day 1. In conclusion, KDS2010 was shown to target the kidney and testis with a no-observed-adverse-effect level of 50 and 30 mg/kg/day for males and females, respectively.

Thirteen-week oral toxicity study of fermented ginseng, GBCK25, in Sprague-Dawley rats.

Ginseng (Panax ginseng) is commonly used in Asia as a medicinal herb. In particular, fermented ginseng, GBCK25, has been recently developed to increase ginsenoside absorption. It also has other beneficial biological effects such as hemodynamic and anti-inflammation functions. Here, we investigated the potential toxicity of GBCK25 in Sprague-Dawley rats following 13 weeks of GBCK25 treatment by oral gavage at doses of 250, 500, or 1000 mg/kg/day and reversible toxic effects over a 4-week recovery phase. Ten male and female rats per group were randomly allocated to the main toxicology groups and five male and female rats per group were allocated to the 0 and 1000 mg/kg/day recovery groups, respectively. There was no mortality; significant clinical toxicity or microscopic findings; and changes in body weight, food consumption, hematological parameters, serum biochemistry, or absolute and relative organ weights in any of the groups. In conclusion, there were no toxicological changes upon repeated oral gavage of GBCK25 at doses of 250, 500, or 1000 mg/kg/day in Sprague-Dawley rats over 13 weeks. The no-observed-adverse-effect level of GBCK25 was 1000 mg/kg/day in both sexes of Sprague-Dawley rat.

The First Human Trial of Transoral Robotic Surgery Using a Single-Port Robotic System in the Treatment of Laryngo-Pharyngeal Cancer.

BACKGROUND: This study aimed to evaluate the feasibility and safety of the DaVinci SP system for performing transoral robotic surgery (TORS) in patients with head and neck cancer. METHODS: From October 2018 to April 2019, the medical records of 41 patients who underwent TORS using the DaVinci SP system were retrospectively reviewed. RESULTS: During TORS, three robotic arms could be used to perform a geometric resection of the lesion in a narrow working space. The mean total operation time was 60 min, and the average time required to set up the robotic system was 10 min or less. All patients successfully underwent TORS. All robotic arms were inserted through a single port, which widened the working space around the patient's head and allowed the operative assistant an easy approach to the patient during the operation. The joggle joint of the robotic arms aided easy manipulation within the confined working space. The joggle joints of the endoscopic arm were controlled through the navigation system, which was very helpful in securing superior visualization of the surgical site, especially in the area of the larynx and the hypopharynx. CONCLUSION: The study confirmed that the DaVinci SP system provided technical advantages above the Si and Xi systems for performing TORS. It was especially helpful in ensuring proper visualization of the surgical field and in performing precise surgery during surgery to the tongue base or the hypopharyngeal lesion.

Fibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition.

Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor.

A Clinical Trial of Combination Neoadjuvant Chemotherapy and Transoral Robotic Surgery in Patients with T3 and T4 Laryngo-Hypopharyngeal Cancer.

BACKGROUND: We conducted a prospective clinical trial of combination neoadjuvant chemotherapy, transoral robotic surgery (TORS), and customized adjuvant therapy in patients with locally advanced laryngo-hypopharyngeal cancer. METHODS: Between September 2008 and August 2016, 35 patients were enrolled in this clinical trial. RESULTS: Twenty patients had hypopharyngeal cancer and 15 had laryngeal cancer. Twenty-nine patients (82.9%) had T3 disease and six patients (17.1%) had T4 disease, while 12 patients (34.3%) had stage III disease and 23 patients (65.7%) had stage IV disease. The 3-year disease-specific survival rate was 82.4% and the 3-year disease-free survival rate was 69.48%. Decannulation was successful in 31 of 34 patients at an average of 18 days postoperatively. Among all patients, 83% exhibited a favorable subjective swallowing status, while five patients (14.4%) became dependent on feeding tubes. CONCLUSIONS: Neoadjuvant chemotherapy combined with TORS and customized adjuvant therapy, based on detailed pathological information, afforded favorable oncological outcomes and preserved organ functionalities in T3-T4 laryngo-hypopharyngeal cancer.

A hot-water extract of Sanguisorba officinalis ameliorates endotoxin-induced septic shock by inhibiting inflammasome activation.

The inflammasome is a multiprotein signaling complex that mediates inflammatory innate immune responses through caspase 1 activation and subsequent IL-1ß secretion. However, because its aberrant activation often leads to inflammatory diseases, targeting the inflammasome holds promise for the treatment of inflammation-related diseases. In this study, it was found that a hot-water extract of Sanguisorba officinalis (HSO) suppresses inflammasome activation triggered by adenosine 5'-triphosphate, nigericin, microbial pathogens, and double stranded DNA in bone marrow-derived macrophages. HSO was found to significantly suppress IL-1ß production in a dose-dependent manner; this effect correlated well with small amounts of caspase 1 and little ASC pyroptosome formation in HSO-treated cells. The anti-inflammatory activity of HSO was further confirmed in a mouse model of endotoxin-induced septic shock. Oral administration of HSO reduced IL-1ß titers in the serum and peritoneal cavity, increasing the survival rate. Taken together, our results suggest that HSO is an inhibits inflammasome activation through nucleotide-binding domain and leucine-rich repeat pyrin domain 3, nucleotide-binding domain and leucine-rich repeat caspase recruitment domain 4 and absent in melanoma 2 pathways, and may be useful for treatment of inflammasome-mediated diseases.

A New Clinical Trial of Neoadjuvant Chemotherapy Combined With Transoral Robotic Surgery and Customized Adjuvant Therapy for Patients With T3 or T4 Oropharyngeal Cancer.

BACKGROUND: A prospective clinical trial of combination neoadjuvant chemotherapy, transoral robotic surgery (TORS), and customized adjuvant therapy for patients with locally advanced oropharyngeal cancer was conducted. METHODS: Between July 2009 and October 2016, 31 patients were enrolled in this clinical trial. RESULTS: The primary lesions were located in the tonsils of 27 patients and in the base of the tongue of 4 patients. Of the 31 patients, 16 (51.6%) were classified as T3 and 15 patients (48.4%) as T4a. Three patients (9.7%) had stage 3 disease, and 28 (90.3%) had stage 4 disease. The 5-year overall survival rate was 78.7%; the 5-year disease-specific survival rate was 85%; and the 5-year disease-free survival rate was 80.8%. At the final follow-up visit, 26 patients were alive with no evidence of disease, and 1 was alive with disease. Four patients died during the study: two of tumor-node-metastasis (TNM)-related disease and two of another condition. All the patients tolerated an oral diet at an average of 7.4 days postoperatively. At the subjective swallowing evaluation using the Functional Outcome Swallowing Scale score, 83.9% of the patients exhibited favorable outcomes. No patient was permanently dependent on a feeding tube. All the patients breathed and phonated in the absence of a permanent tracheotomy at the final follow-up evaluation. CONCLUSIONS: The treatment strategy in this study afforded good oncologic and functional outcomes for patients with locally advanced oropharyngeal cancer. Although future large-scale multicenter studies with longer follow-up periods are needed, this study showed that neoadjuvant chemotherapy combined with TORS is useful for treating advanced oropharyngeal cancer.

Clinicopathological factors influencing the outcomes of surgical treatment in patients with T4a hypopharyngeal cancer.

BACKGROUND: The purpose of this study was to determine prognostic factors influencing outcomes of surgical treatment in patients with T4a hypopharyngeal cancer. METHODS: The present study enrolled 93 patients diagnosed with T4a hypopharyngeal cancer who underwent primary surgery between January 2005 and December 2015 at six medical centers in Korea. Primary tumor sites included pyriform sinus in 71 patients, posterior pharyngeal wall in 14 patients, and postcricoid region in 8 patients. Seventy-two patients received postoperative radio(chemo)therapy. RESULTS: Five-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 38% and 45%, respectively. In univariate analysis, 5-year DFS was found to have significant and positive correlations with margin involvement (p < 0.001) and extracapsular spread (p = 0.025). Multivariate analysis confirmed that margin involvement (hazard ratio (HR): 2.81; 95% confidence interval (CI): 1.49-5.30; p = 0.001) and extracapsular spread (HR: 2.08; 95% CI: 1.08-3.99; p = 0.028) were significant factors associated with 5-year DFS. In univariate analysis, cervical lymph node metastasis (p = 0.048), lymphovascular invasion (p = 0.041), extracapsular spread (p = 0.015), and esophageal invasion (p = 0.033) were significant factors associated with 5-year DSS. In multivariate analysis, extracapsular spread (HR: 2.98; 95% CI: 1.39-6.42; p = 0.005) and esophageal invasion (HR: 2.87; 95% CI: 1.38-5.98; p = 0.005) remained significant factors associated with 5-year DSS. CONCLUSION: Margin involvement and extracapsular spread are factors influencing recurrence while extracapsular spread and esophageal invasion are factors affecting survival in patients with T4a hypopharyngeal cancer treated by primary surgery.

Combined Oral Medroxyprogesterone/Levonorgestrel-Intrauterine System Treatment for Women With Grade 2 Stage IA Endometrial Cancer.

OBJECTIVE: The aim of this study was to evaluate the oncologic and pregnancy outcomes of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment in young women with grade 2-differentiated stage IA endometrial adenocarcinoma who wish to preserve fertility. METHODS: We retrospectively reviewed the medical records of patients with grade 2 stage IA endometrial adenocarcinoma who had received fertility-sparing treatment at CHA Gangnam Medical Center between 2011 and 2015. All of the patients were treated with combined oral MPA (500 mg/d)/LNG-IUS, and follow-up dilatation and curettage were performed every 3 months. RESULTS: A total of 5 patients were included in the study. The mean age was 30.4 ± 5.3 years (range, 25-39 years). After a mean treatment duration of 11.0 ± 6.2 months (range, 6-18 months), complete response (CR) was shown in 3 of the 5 patients, with partial response (PR) in the other 2 patients. One case of recurrence was reported 14 months after achieving CR. This patient was treated again with combined oral MPA/LNG-IUS and achieved CR by 6 months. The average follow-up period was 44.4 ± 26.2 months (range, 12-71 months). There were no cases of progressive disease. No treatment-related complications arose. CONCLUSIONS: Combined oral MPA/LNG-IUS treatment is considered to be a reasonably effective fertility-sparing treatment of grade 2 stage IA endometrial cancer. Although our results are encouraging, it is preliminary and should be considered with experienced oncologists in well-defined protocol and with close follow-up.

A hot water extract of Aralia cordata activates bone marrow-derived macrophages via a myeloid differentiation protein 88-dependent pathway and protects mice from bacterial infection.

In traditional Asian medicine, Aralia cordata (AC) is a known as a pain reliever and anti-inflammatory drug. Although several of its biological activities have been reported, the immunomodulatory effects of a hot water extract of AC (HAC) have not yet been described. The aim of this study was to investigate whether HAC modulates the activation of macrophages, which play important roles in innate immune responses against microbial pathogens, and if so, to determine the molecular mechanisms by which HAC mediates this process. It was found that HAC activates bone marrow-derived macrophages (BMDM) and increases amounts of nitric oxide and proinflammatory cytokines in a dose-dependent manner. In addition, HAC was found to induce phosphorylation of NF-κB and mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinases, extracellular signal-regulated kinases and p38. Interestingly, these effects were absent in BMDM prepared from myeloid differentiation protein 88-knockout mice. Polysaccharides from HAC exerted stronger immunostimulatory effects than HAC itself. Furthermore, orally administered HAC clearly enhanced clearance of the intracellular pathogen Listeria monocytogenes by boosting innate immune responses. These results demonstrate that HAC exerts immunostimulatory effects through the TLR/MyD88 and NF-κB/MAPK signal transduction pathways.

Evidence for No Significant Impact of Müllerian Anomalies on Reproductive Outcomes of Twin Pregnancy in Korean Women.

The present article aimed to evaluate the impact of congenital Müllerian anomalies (MA) on twin pregnancy after 24 gestational weeks in Korean women. All records of twin pregnancies in a large maternity hospital in Korea between January 2005 and July 2013 were analyzed. Patients with monochorionic monoamniotic (MCMA) twins, non-Korean patients, patients with twins delivered prior to 24 gestational weeks, and patients with miscarriage of one fetus or intrauterine fetal death (IUFD) before 24 gestational weeks were excluded from data analysis. In total, 1,422 women with twin pregnancy were eligible for data analysis, including 17 (1.2%) who had a known congenital MA (septate uterus, bicornuate uterus, arcuate uterus, and unicornuate uterus). Except for the mode of conception, baseline demographics were similar between women with MA and those without MA. No significant differences were found in pregnancy outcomes of gestational age at delivery (p = .86), birth weight of smaller and larger twins (p = .54 and p = .65), and number of twins with birth weight <5th percentile for gestational age (p = .43).The rates of obstetrical complications such as pre-eclampsia, gestational diabetes mellitus (GDM), placenta previa, cerclage, IUFD, and postpartum hemorrhage were not significantly different between the two groups either. We concluded that the presence of congenital MA may not increase obstetrical risks in outcomes of pregnancy of twins delivered after 24 gestational weeks.