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Endoplasmic reticulum (ER) stress is a condition in which the ER protein-folding machinery is impaired, leading to the accumulation of improperly folded proteins and triggering an unfolded-protein response. Excessive ER stress causes cell death and contributes to the development of chronic diseases. Interestingly, there is a bidirectional relationship between ER stress and the nuclear factor-kappa B (NF-κB) pathway. Curcumin, a natural polyphenolic compound found in Curcumae radix, exerts its neuroprotective effects by regulating ER stress and inflammation. Therefore, investigating the potential protective and regulatory effects of curcumin on ER stress, inflammation, and neurodegeneration under chronic neuroinflammatory conditions is of great interest. Mice were pretreated with Curcumae radix extract (CRE) for 19 days and then treated with CRE plus lipopolysaccharide for 1 week. We monitored pro-inflammatory cytokine levels in the serum and ER stress-, inflammation-, and neurodegeneration-related markers in the mouse cerebrum and hippocampus using Western blotting and qRT-PCR. CRE reduced Interleukin-1 beta levels in the blood and brain of mice with lipopolysaccharide-induced chronic inflammation. CRE also suppressed the expression of markers related to the ER stress and NF-κB signaling pathways. The expression of neurodegeneration-related markers was reduced in the mouse cerebrum and hippocampus. CRE exerts neuroprotective effects under chronic inflammatory conditions via multifaceted anti-inflammatory and ER stress-pathway regulatory mechanisms.

Background/Aims Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients. Methods Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort. Results 180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence

Abstract Circular RNAs (circRNAs) represent potential biomarkers because of their highly stable structure and robust expression pattern in clinical samples. The aim of this study was to evaluate the expression of a recently identified circRNA, hsa_circ_0005986; determine its clinical significance; and evaluate its potential as a biomarker of hepatocellular carcinoma (HCC). We evaluated hsa_circ_0005986 expression in 123 HCC tissue samples, its clinical significance, and its association with patients’ clinicopathological characteristics and survival. Hsa_circ_0005986 expression was downregulated in HCC tissues. Low hsa_circ_0005986 expression was more common in tumors larger than 5 cm [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.51–6.76; p = 0.002], advanced TNM stage (III/IV; OR, 2.39; 95% CI, 1.16–4.95; p = 0.018), and higher BCLC stage (B/C; OR, 2.71; 95% CI, 1.30–5.65; p = 0.007). High hsa_circ_0005986 expression was associated with improved survival and was an independent prognostic factor for overall [hazard ratio (HR), 0.572; 95% CI, 0.339–0.966; p = 0.037] and progression-free (HR, 0.573; 95% CI, 0.362–0.906; p = 0.017) survival. Moreover, the circRNA–miRNA–mRNA network was constructed using RNA-seq/miRNA-seq data and clinical information from TCGA-LIHC dataset. Our findings indicate a promising role for hsa_circ_0005986 as a prognostic biomarker in patients with HCC.

Background: Few studies investigated the prescription patterns of traditional Korean medicine (TKM) therapies for PCOS in clinical practice. The purpose of this study was to identify the common symptoms, herbal prescription patterns and types of adjunctive treatment for treating polycystic ovary syndrome (PCOS) in major traditional Korean medicine (TKM) hospitals. Methods: A retrospective chart review of PCOS patients was used for the study. The study involved the analysis of medical records (ICD-10, polycystic ovary syndrome: E28.2) from four TKM-based university hospitals in South Korea. Results: A total of 120 PCOS patients were analyzed. We found that PCOS patients had a wide range of symptoms, including menstrual irregularity, oligomenorrhea, amenorrhea, acne, infertility, and metrorrhagia. The most commonly prescribed prescriptions for PCOS treatment were Chokyung-san (Tiaojing-san), Gamiguibi-tang (Jiawei Guipi-tang), and Changbudodam-tang (Cangfu Daotan-tang). In addition, patients were most often treated with adjunctive acupuncture and moxibustion. Conclusion: Our study presents the major gynecological herbal prescriptions and other adjunctive therapies used for the treatment of PCOS in TKM-based hospitals. However, further pharmacological investigations and effective clinical trials should be developed to ensure the objectivity of efficacy assessments.

Background: This study aimed to examine the evidence for the effect of Lepidium meyenii Walp. [Brassicaceae] (L. meyenii W.), known as maca, on improving semen quality.Methods: Nine databases were searched for randomized controlled trials (RCTs) that examined the parameters for improvements in semen quality, regardless of the type of L. meyenii W. The risk of bias (ROB) among the studies was evaluated according to the Cochrane ROB tool.Results: Five RCTs met all of the inclusion criteria. Three RCTs showed mixed efficacy of maca in improving semen quality parameters, including sperm concentration and sperm motility, in men experiencing infertility. The meta-analysis also failed to show the efficacy of maca in increasing the sperm concentration compared to the placebo (weighted mean difference, 2.22, 95% confidence interval −2.94 to 7.37, p = 0.4). Two other RCTs also showed mixed effects of maca on several semen quality parameters in healthy men.Conclusion: The evidence from the included studies suggests unclear effects of maca on semen quality parameters in both men experiencing infertility and healthy men. However, the total number of RCTs and the total sample size were too small to draw firm conclusions.

Introduction: Polycystic Ovarian Syndrome (PCOS) is known to be an endocrine state that is characterized by oligomenorrhea, hyperandrogenism, and highly cystic follicles in the ovaries. The use of food ingredients and traditional medicine in Asian countries is well known, and previous studies have shown that Ecklonia cava K. [Alariaceae] (EC) is able to alleviate PCOS symptoms. D-Chiro-inositol (DCI) administration in pathologies where steroid biosynthesis is a crucial factor, i.e., PCOS, has provided satisfactory results.Methods: Therefore, we studied the synergistic effects of the two previously known active compounds. In rats with letrozole-induced PCOS, we focused on alternative therapies using EC and/or DCI extracts to alleviate ovarian failure.Results: As a nonsteroidal aromatase inhibitor, letrozole inhibits the conversion of testosterone to estrogen and subsequently causes PCOS. We divided 6-week-old female mice into the following six groups and evaluated them: vehicle, PCOS, PCOS + MET (metformin), PCOS + DCI, PCOS + EC, and PCOS + DCI + EC. In our study, PCOS rats treated with EC and DCI had low serum LH and T levels and low serum levels of inflammatory cytokines such as TNFα and IL-6. These treatments also appeared to regulate the production of factors that affect follicle formation and inflammation in the ovaries.Conclusion: We concluded that EC extract and/or DCI administration influenced aromatase production and reduced LH and T stimulation, and cotreatment with EC and DCI consequently restored ovarian dysfunction or anti-inflammatory responses in rats with PCOS-like symptoms.

With the emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants, escaping vaccine-induced immunity is a concern. Three vaccination schedules, homologous or heterologous, have been initially applied due to an insufficient supply of vaccines in Korea. We investigated neutralizing activities against Omicron and Delta variants in each schedule. Three schedules using three doses of the BNT162b2 (BNT) or the ChAdOx1 (ChAd) vaccines include ChAd-ChAd-BNT, ChAd-BNT-BNT, and BNT-BNT-BNT. Neutralizing activities were evaluated using plaque-reduction neutralization test (PRNT) against wild type (WT) SARS-CoV-2, Delta variant, and Omicron variant. A total of 170 sera from 75 participants were tested, and the baseline characteristics of participants were not significantly different between groups. After the 2nd vaccine dose, geometric mean titers of PRNT ND50 against WT, Delta, and Omicron were highest after ChAd-BNT vaccination (2,463, 1,097, and 107) followed by BNT-BNT (2,364, 674, and 38) and ChAd-ChAd (449, 163, and 25). After the 3rd dose of BNT, the increase of PRNT ND50 against WT, Delta, and Omicron was most robust in ChAd-ChAd-BNT (4,632, 988, and 260), while the BNT-BNT-BNT group showed the most augmented neutralizing activity against Delta and Omicron variants (2,315 and 628). ChAd-BNT-BNT showed a slight increase of PRNT ND50 against WT, Delta, and Omicron (2,757, 1,279, and 230) compared to the 2nd dose. The results suggest that a 3rd BNT booster dose induced strengthened neutralizing activity against Delta and Omicron variants. The waning of cross-reactive neutralizing antibodies after the 3rd dose and the need for additional boosting should be further investigated.

Background: Integrative herbal medicine has been reported to have beneficial effects in the treatment of coronavirus disease 2019 (COVID-19).Aim: To compile up-to-date evidence of the benefits and risks of herbal medicine for the treatment of COVID-19 symptoms.Methods: Eleven databases, including PubMed, Cochrane Register of Controlled Trials (CENTRAL), Embase, Allied and Complementary Medicine Database (AMED), Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Chinese Science and Technique Journals Database (VIP), Research Information Service System (RISS), Korean Medical database (KMBase), Korean Association of Medical Journal database (KoreaMed), and OASIS database, were searched from 15 June, 2020, until 28 March 2022. Randomized controlled trials (RCTs), published in any language, reporting the efficacy and safety outcomes of herbal medicine in patients of all ages with a PCR-confirmed diagnosis of COVID-19 were included in this analysis. Data extraction and quality assessments were performed independently.Results: Random-effects meta-analyses showed evidence of favorable effects of treatment with herbal medicine when added to standard treatment, versus standard treatment alone, on the total effective rate (p = 0.0001), time to remission from fever (p < 0.00001), rate of remission from coughing (p < 0.0001), fatigue (p = 0.02), sputum production (p = 0.004), improvement of manifestations observed on chest computed tomography scans (p < 0.00001), incidence of progression to severe COVID-19 (p = 0.003), all-cause mortality (p = 0.003), time to a negative COVID-19 coronavirus test (p < 0.0001), and duration of hospital stay (p = 0.0003). There was no evidence of a difference between herbal medicine added to standard treatment, versus standard treatment alone, on the rate of remission from symptoms such as a fever, sore throat, nasal congestion and discharge, diarrhea, dry throat, chills, and the rate of conversion to a negative COVID-19 coronavirus test. Meta-analysis showed no evidence of a significant difference in adverse events between the two groups. There was an unclear risk of bias across the RCTs included in this analysis, indicating that most studies had methodological limitations.Conclusion: Current evidence suggests that herbal medicine added to standard treatment has potential benefits in the treatment of COVID-19 symptoms but the certainty of evidence was low.

Abstracts: Study region: Euiam Lake in the Republic of Korea Study focus: This study establishes a framework to prioritize total phosphorus (TP) management strategies based on machine learning (ML). A comparative analysis is conducted to evaluate the performance of four ML methods: random forest (RF), extreme gradient boosting (XGBoost), deep neural network (DNN), and long short-term memory (LSTM). The LSTM-based model is selected as the optimal predictive model of TP concentration in Euiam Lake (E_TP) on seasons (May to October) with high rainfall and inflow from two upstream dams (Chuncheon Dam and Soyanggang Dam). We also perform a gradient-based analysis to figure out the most influential factors on E_TP using the LSTM model. The top four priority factors are TP concentrations and suspended solids concentrations in the upstream dams. This application of the gradient-based analysis enables the predictive model to discuss quantitative reductions in the priorities. Based on these numerical results, we anticipate that the proposed framework can enhance the feasibility of management practices for achieving the water quality management goal of the study region. New hydrological insights: This study demonstrates that a robust predictive model can be developed for a serial impoundment system with distinct seasonal characteristics of rainfall, temperature, and water quality, thereby facilitating the selection of management priorities. Based on the predictive model results, we conclude that it is the key for managing the target TP concentration to prioritize the incoming TP concentrations and determine the quantitative

Background/Aims: This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. Methods: A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. Results: Among the 100 patients, 88% achieved a sustained virological response (SVR) 12 weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (

Due to the highly immunogenic nature of renal cell carcinoma (RCC), the tumor microenvironment (TME) is enriched with various innate and adaptive immune subsets. In particular, gamma-delta (γδ) T cells can act as potent attractive mediators of adoptive cell transfer immunotherapy because of their unique properties such as non-reliance on major histocompatibility complex expression, their ability to infiltrate human tumors and recognize tumor antigens, relative insensitivity to immune checkpoint molecules, and broad tumor cytotoxicity. Therefore, it is now critical to better characterize human γδ T-cell subsets and their mechanisms in RCCs, especially the stage of differentiation. In this study, we aimed to identify γδ T cells that might have adaptive responses against RCC progression. We characterized γδ T cells in peripheral blood and tumor-infiltrating lymphocytes (TILs) in freshly resected tumor specimens from 20 RCC patients. Furthermore, we performed a gene set enrichment analysis on RNA-sequencing data from The Cancer Genome Atlas (TCGA) derived from normal kidneys and RCC tumors to ascertain the association between γδ T-cell infiltration and anti-cancer immune activity. Notably, RCC-infiltrating CD3low Vγ9Vδ1 T cells with a terminally differentiated effector memory phenotype with up-regulated activation/exhaustion molecules were newly detected as predominant TILs, and the cytotoxic activity of these cells against RCC was confirmed in vitro. In an additional analysis of the TCGA RCC dataset, γδ T-cell enrichment scores correlated strongly with those for CTLs, Th1 cells, “exhausted” T cells, and M1 macrophages, suggesting active involvement of γδ T cells in anti-tumor rather than pro-tumor activity, and Vδ1 cells were more abundant than Vδ2 or Vδ3 cells in RCC tumor samples. Thus, we posit that Vγ9Vδ1 T cells may represent an excellent candidate for adoptive immunotherapy in RCC patients with a high risk of relapse after surgery.

Background/Aims The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT. Methods Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA >20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of

Abstract The risk of malnutrition in acute kidney injury and mortality in coronary artery disease patients has not been studied. This study aimed to evaluate whether nutritional status assessed by Onodera’s prognostic nutritional index (PNI) was related to percutaneous coronary intervention (PCI) outcomes. A total of 3731 patients who received PCI between January 2010 and December 2018 were included. The relationship between PNI at the time of PCI and the occurrence of contrast-associated acute kidney injury (AKI) and all-cause death was evaluated using logistic regression and Cox proportional hazards models, respectively. AKI occurred in 271 patients (7.3%). A low PNI was independently associated with an increased risk of AKI on multivariate logistic regression analysis (OR 0.96, 95% CI 0.94–0.98, P = 0.001). During the median follow-up of 4.3 years, Kaplan–Meier analysis showed that patients with AKI/low PNI

Background: Trans-arterial radioembolization (TARE) has shown promising results in treating hepatocellular carcinoma (HCC). We identified independent predictors of radiological complete response (CR) in patients with intrahepatic HCC who were treated with TARE. Methods: Patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited. CR was defined according to the modified Response Evaluation Criteria in Solid Tumors. Cox regression analysis was used to determine independent predictors of CR. Results: The median age of study participants (83 men and 19 women) was 64.3 years. The mean survival after TARE was 55.5 months, and 21 (20.6%) patients died during the study period. Patients who achieved CR (14 patients, 13.7%) had significantly higher serum albumin level (median 4.1 vs. 3.9 g/dL), lower total bilirubin level (median 0.6 vs. 0.7 mg/dL), lower aspartate aminotransferase level (median 30.0 vs. 43.0 IU/L), lower alkaline phosphatase level (median 79.0 vs. 103.0 IU/L), lower alpha-fetoprotein level (median 12.7 vs. 39.9 ng/mL), lower des-gamma-carboxyprothrombin level (median 575.5 vs. 2772.0 mAU/mL), lower model for end-stage liver disease (MELD) score (median 6.0 vs. 7.0), and smaller maximal tumor diameter (median 6.3 vs. 9.0 cm) compared to those who did not achieve CR (all p < 0.005). Multivariate Cox regression analysis showed that lower MELD score (hazard ratio (HR) = 0.436, p = 0.015) and maximal tumor size < 9 cm (HR = 11.180, p = 0.020) were independent predictors of an increased probability of radiological CR after TARE. Conclusions: Low MELD score and small maximal tumor size were independently associated with an increased probability of CR after TARE in patients with intrahepatic HCC.

Background/Aims: The hepatic steatosis index (HSI) is a noninvasive method to assess the severity of hepatic steatosis. Antiviral therapy (AVT) can impact aspartate aminotransferase and alanine aminotransferase levels, which are the main components of the HSI. Thus, we investigated the accuracy of the HSI in detecting hepatic steatosis in patients with chronic hepatitis B (CHB) receiving AVT, compared with those not receiving AVT and in those with nonalcoholic fatty liver disease (NAFLD). Methods: Patients with CHB or NAFLD who underwent a magnetic resonance imaging proton density fat fraction (MRI-PDFF) evaluation between March 2010 and March 2019 were recruited. Hepatic steatosis was diagnosed when the PDFF exceeded 5%. Area under the receiver operating characteristic curve (AUROC) analysis was used to assess the diagnostic accuracy of the HSI in the detection of hepatic steatosis. Results: The mean age of the study population (189 men and 116 women; 244 with CHB [184 with and 60 without AVT] and 61 with NAFLD) was 55.6 years. The AUROC values for detecting hepatic steatosis were similar between patients with CHB (0.727; p

Background Lymph node fine-needle aspiration (LN FNA) cytology indicates necrosis in various diseases. Dominant necrotic features make the diagnosis of underlying conditions very difficult. Methods We retrospectively reviewed 460 patients who underwent cervical LN aspiration cytology that revealed necrotic findings at Keimyung University Dongsan Hospital in Daegu, Korea, from 2003–2017. Each specimen was evaluated and analyzed in association with the clinical findings, biopsy findings, and/or other ancillary tests, including acid-fast bacilli staining and molecular testing for Mycobacterium tuberculosis. Results When necrotic features were noted upon cervical LN FNA cytology, the most common pathologic LN FNA category was necrosis alone (31.5%). The second most common category was granulomatous inflammation (31.3%), followed by Kikuchi disease (20.0%) and malignant neoplasm (8.7%). In cases where the cervical LN FNA revealed necrosis alone, the most common final diagnosis was tuberculosis. In young patients, Kikuchi disease should be considered as one cervical LN FNA category, while metastatic carcinoma should be suspected in older patients. Conclusions Even when necrosis alone is observed in LN FNA cytology, it is important to determine the cause through further evaluation.

BackgroundTraditional, Complementary and Integrative Medicine (TCIM) has been reported to use for symptom management of coronavirus disease 2019 (COVID-19). The objective of this review was to identify the overall usage prevalence of TCIM interventions for COVID-19.MethodsSurveys on the general population and observational studies on the COVID-19 patient chart review were located in the search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases in September 2021. Observational studies, such as cross-sectional studies, surveys, cohort studies and hospital-based patient case reviews, published in any language, reporting the usage of TCIM in the patients with COVID-19 or the general population during the COVID-19 pandemic were included in this review. Data screening and extraction were performed independently by two reviewers. The reporting quality of the included studies was assessed with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement. To conduct a meta-analysis of the usage prevalence of various TCIM interventions, the effect size of the proportion for each intervention was calculated with the inverse variance method. The main outcome was usage prevalence of TCIM interventions among patients with COVID-19 or the general population during the COVID-19 pandemic.ResultsA total of 62 studies were included in this review. The overall TCIM usage prevalence was estimated to be 0.64 (95% CI 0.54–0.73). The overall prevalence did not differ between the population-based survey (0.65, 95% CI 0.48–0.81) and the hospital-based patient case review (0.63, 95% CI 0.52–0.73). Statistical heterogeneity and comparatively low quality in reporting were observed, which should be cautiously considered when interpreting the results.ConclusionVarious TCIM interventions were reported to be used with comparatively high frequency. Future international collaborative research might overcome the main limitation of this study, i.e., the heterogeneity of the included data.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278452, identifier: CRD42021278452.

Evidence mapping of systematic reviews (SRs) systematically and comprehensively identifies, organizes, and summarizes the distribution of scientific evidence in a field. The aim of this evidence map is to provide a synopsis of the best clinical practices and interventions in stroke rehabilitative care and to identify areas with a paucity of evidence to guide future research. PubMed, EMBASE, CDSR, six Korean databases, and two Chinese databases were searched for SRs evaluating the effectiveness of any stroke rehabilitation intervention through October 2021. The quality of the SRs was assessed using AMSTAR 2. A bubble plot was used to graphically display clinical topics, the number of articles, the number of patients included, confidence, and effectiveness. In total, ninety-five SRs were identified; however, after methodological analysis, only 48 had sufficient quality to be included. In total, forty-eight SRs were included in the evidence mapping. The overall search identified SRs from 2015 to 2021. A total of four SRs focused on post-stroke cognitive impairment, whereas the other forty-four SRs focused on post-stroke motor function. In total, nineteen different traditional Chinese medicine (TCM) intervention modalities were included. Acupuncture was the most commonly used treatment. Overall, the quality of the included SRs was low or very low. Most SRs concluded that TCM interventions may have potential benefits in stroke rehabilitation. The results were more promising when acupuncture was used for shoulder–hand syndrome. However, the identified reviews cautioned that firm conclusions cannot be drawn. The evidence map provides a visual overview of the research volume and content involving TCM interventions in stroke rehabilitation. Evidence mapping can facilitate the process of knowledge translation from scientific findings to researchers and policymakers and possibly reduce waste in research.

Identification of non-alcoholic steatohepatitis (NASH) with high activity and fibrosis is a major priority in patients with non-alcoholic fatty liver disease. We validated the predictive value of the FibroScan-aspartate aminotransferase (FAST) score and other non-invasive fibrosis surrogates in predicting high-risk NASH criteria. This multicenter retrospective study recruited 251 biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients (132 [52.6%] men) between 2011 and 2014. The FAST score was calculated using transient elastography data and aspartate aminotransferase (AST) levels. The NAFLD fibrosis score (NFS), fibrosis-4 index (FIB-4), and AST to platelet ratio index (APRI) were calculated using biochemical data. The area under the receiver operating characteristic curves (AUCs) of the FAST score, liver stiffness, NFS, FIB-4, and APRI were 0.752, 0.718, 0.609, 0.650, and 0.722 for NAFLD activity score (NAS) ≥5 (n = 117, 46.6%); 0.788, 0.754, 0.649, 0.701, and 0.747 for fatty liver inhibition of progression-NASH with histologic activity ≥3 (n = 202, 80.5%); 0.807, 0.806, 0.691, 0.732, and 0.760 for severe disease with activity ≥3 and/or fibrosis ≥3 (n = 132, 52.6%); and 0.714, 0.812, 0.748, 0.738, and 0.669 for NASH with NAS ≥4 and fibrosis ≥2 (n = 70, 27.9%), respectively. The FAST score had the highest AUC for the most high-risk NASH criteria, except for in predicting NAS ≥4 and fibrosis ≥2. The liver stiffness value showed consistently acceptable performance in predicting all high-risk NASH criteria. The FAST score has acceptable performance in identifying high-risk NASH. However, liver stiffness alone was not inferior to the FAST score.

Background & Aims: Accurate hepatocellular carcinoma (HCC) risk prediction facilitates appropriate surveillance strategy and reduces cancer mortality. We aimed to derive and validate novel machine learning models to predict HCC in a territory-wide cohort of patients with chronic viral hepatitis (CVH) using data from the Hospital Authority Data Collaboration Lab (HADCL). Methods: This was a territory-wide, retrospective, observational, cohort study of patients with CVH in Hong Kong in 2000–2018 identified from HADCL based on viral markers, diagnosis codes, and antiviral treatment for chronic hepatitis B and/or C. The cohort was randomly split into training and validation cohorts in a 7:3 ratio. Five popular machine learning methods, namely, logistic regression, ridge regression, AdaBoost, decision tree, and random forest, were performed and compared to find the best prediction model. Results: A total of 124,006 patients with CVH with complete data were included to build the models. In the training cohort (n = 86,804; 6,821 HCC), ridge regression (area under the receiver operating characteristic curve [AUROC] 0.842), decision tree (0.952), and random forest (0.992) performed the best. In the validation cohort (n = 37,202; 2,875 HCC), ridge regression (AUROC 0.844) and random forest (0.837) maintained their accuracy, which was significantly higher than those of HCC risk scores: CU-HCC (0.672), GAG-HCC (0.745), REACH-B (0.671), PAGE-B (0.748), and REAL-B (0.712) scores. The low cut-off (0.07) of HCC ridge score (HCC-RS) achieved 90.0% sensitivity and 98.6% negative predictive value (NPV) in the validation cohort. The high cut-off (0.15) of HCC-RS achieved high specificity (90.0%) and NPV (95.6%); 31.1% of patients remained indeterminate. Conclusions: HCC-RS from the ridge regression machine learning model accurately predicted HCC in patients with CVH. These machine learning models may be developed as built-in functional keys or calculators in electronic health systems to reduce cancer mortality. Lay summary: Novel machine learning models generated accurate risk scores for hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis. HCC ridge score was consistently more accurate than existing HCC risk scores. These models may be incorporated into electronic medical health systems to develop appropriate cancer surveillance strategies and reduce cancer death.

Background/Aims: Sarcopenia is associated with liver fibrosis in patients with nonalcoholic fatty liver disease and chronic hepatitis B. We investigated the association between sarcopenia and hepatic fibrotic burden in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM who had received a comprehensive medical health checkup were recruited. Muscle mass was assessed using computed tomography. Fibrotic burden was assessed using the fibrosis-4 index (FIB-4). The study population was divided by quartile stratification of the lumbar skeletal muscle index (LSMI). Results: Among 309 patients with T2DM, 75 (24.3%) had sarcopenia. These patients were significantly older and had higher FIB-4, whereas they had significantly lower body mass index (BMI) and LSMI than patients without sarcopenia (all p

Abstract Background Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages. Results We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCOhigh TAMs induce a phenotypic shift towards mesenchymal cellular state of glioma stem cells, promoting both invasive and proliferative activities, as well as therapeutic resistance to irradiation. MARCOhigh TAMs also significantly accelerate tumor engraftment and growth in vivo. Moreover, both MA-TAM master regulators and their target genes are significantly correlated with poor clinical outcomes and are often associated with genomic aberrations in neurofibromin 1 (NF1) and phosphoinositide 3-kinases/mammalian target of rapamycin/Akt pathway (PI3K-mTOR-AKT)-related genes. We further demonstrate the origination of MA-TAMs from peripheral blood, as well as their potential association with tumor-induced polarization states and immunosuppressive environments. Conclusions Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy.

Purpose: Ginseng has been used as a tonic to improve overall health, restore balance in the body, help the body to heal itself, reduce stress, boost energy, and enhance the immune system. The aim of this review was to assess current evidence that ginseng improves sperm quality. Materials and Methods: We searched twelve databases (PubMed, EMBASE, AMED, the Cochrane Library, five Korean medical databases, and three Chinese medical databases), using a cut-off date of 1st December 2019. We included clinical studies in which healthy men or men with fertility issues were treated with ginseng. We used Cochrane’s risk of bias (ROB) tool to assess the ROB in the studies examined. Results: From two-hundred and nineteen potentially eligible studies, just five relevant studies were selected (two randomized clinical trials [RCTs], one controlled clinical trial [CCT], and two observational studies). Of these studies, one RCT reported some positive results when using Korean red ginseng to improve sperm quality in infertile men. In addition, the other RCT reported that the effects of ginseng on sperm quality were equivalent to those found when valerian tablets are taken by healthy people. One CCT and two uncontrolled observational studies, however, did not demonstrate the clear effectiveness of ginseng in improving sperm quality in infertile men. Conclusions: Currently, there are few trials investigating the efficacy of ginseng for improving sperm quality. The available studies demonstrate a high ROB. It can be suggested that overall, the evidence regarding ginseng improving sperm quality is limited.

Epidermoid cysts are commonly encountered benign lesions in the field of plastic surgery, but their malignant transformation into squamous cell carcinoma (SCC) is extremely rare. A 68-year old woman with a cystic mass on her left lower back presented to our department. We excised the lesion under the suspicion of an epidermoid cyst or metastatic colon cancer based on the patient’s medical history. The skin defect was covered with a split-thickness skin graft, and histopathological evaluation revealed the presence of SCC. Because of the low incidence of SCC arising from an epidermoid cyst, the mechanism of transformation of such cysts to SCC and the prognosis of this condition have not yet been well established. We therefore share the details of this rare case to contribute to the growing base of knowledge about SCC that arises from an epidermoid cyst.

Abstract Background Tumor cell-intrinsic mechanisms and complex interactions with the tumor microenvironment contribute to therapeutic failure via tumor evolution. It may be possible to overcome treatment resistance by developing a personalized approach against relapsing cancers based on a comprehensive analysis of cell type-specific transcriptomic changes over the clinical course of the disease using single-cell RNA sequencing (scRNA-seq). Methods Here, we used scRNA-seq to depict the tumor landscape of a single case of chemo-resistant metastatic, muscle-invasive urothelial bladder cancer (MIUBC) addicted to an activating Harvey rat sarcoma viral oncogene homolog (HRAS) mutation. In order to analyze tumor evolution and microenvironmental changes upon treatment, we also applied scRNA-seq to the corresponding patient-derived xenograft (PDX) before and after treatment with tipifarnib, a HRAS-targeting agent under clinical evaluation. Results In the parallel analysis of the human MIUBC and the PDX, diverse stromal and immune cell populations recapitulated the cellular composition in the human and mouse tumor microenvironment. Treatment with tipifarnib showed dramatic anticancer effects but was unable to achieve a complete response. Importantly, the comparative scRNA-seq analysis between pre- and post-tipifarnib-treated PDX revealed the nature of tipifarnib-refractory tumor cells and the tumor-supporting microenvironment. Based on the upregulation of programmed death-ligand 1 (PD-L1) in surviving tumor cells, and the accumulation of multiple immune-suppressive subsets from post-tipifarnib-treated PDX, a PD-L1 inhibitor, atezolizumab, was clinically applied; this resulted in a favorable response from the patient with acquired resistance to tipifarnib. Conclusion We presented a single case report demonstrating the power of scRNA-seq for visualizing the tumor microenvironment and identifying molecular and cellular therapeutic targets in a treatment-refractory cancer patient.

Abstract This study aims to present a comprehensive model that effectively explains dissatisfaction, complaint behavior, and revisiting intentions of hair service consumers through an empirical analysis. In order to empirically verify the conceptual model, a questionnaire was developed based on previous studies and responses that were collected through an online survey agency. Subjects were Korean female consumers in their 20s to 50s who experienced dissatisfaction with hair services in the salons they visited during the past year. The conceptual model suggested in the theoretical research was analyzed empirically through the structural equation modeling (SEM) test and finally suggested after ordering, eliminating unnecessary paths. According to the results, dissatisfaction with the hair service significantly affects the complaint behavior and the revisiting intentions while the complaint behavior has a mediating effect between dissatisfaction and the revisiting intentions. Analysis showed that dissatisfaction with human response services and private complaint behaviors are the factors that most negatively influence revisiting intentions. It was confirmed that businesses should focus on the management of the customer service delivered by the employees and on word of mouth. Public complaint behavior was proven to increase revisiting intentions of consumers, needing more attention. This study aims to provide plausible reasons and objective materials to the establishment of a solid theoretical base for the research on dissatisfaction, complaint behavior, and revisiting intentions of hair service consumers. It is expected that the results of this study will help create differentiated marketing strategies for unsatisfied and complaining consumers.

Background Attention deficit hyperactivity disorder (ADHD) patients often use complementary and alternative medicine to treat symptoms, and acupuncture is one option. This systematic review aims to assess whether acupuncture is an effective treatment for attention deficit hyperactivity disorder (ADHD). Methods We will search nine databases from their inception: PubMed, AMED, CINAHL, EMBASE, the Cochrane Central Register of Controlled Trials, RISS, KoreaMed, KISS, and the China National Knowledge Infrastructure database. Two investigators will independently review the selected studies, extract the data, and analyze them. The Cochrane Risk of Bias Assessment Tool will be used to assess the risk of bias. Discussion Because this is a systematic review, no ethical approval is needed. The systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to support health policy and practice. Trial registration number Reviewregistry1345.

Background and Objectives: Attention-deficit hyperactivity disorder (ADHD) is a common childhood disorder characterized by inattention, hyperactivity, and impulsivity. However, it is uncertain whether the use of acupuncture (AT) in children with ADHD is supported by the current evidence. This review aims to provide updated evidence of the effectiveness of acupuncture in children with ADHD. Methods: Nine databases were searched from their inception to 28 July 2022. Two authors independently screened potentially eligible studies. The quality assessment of the selected studies was performed using Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). The characteristics of the included studies were presented in a tabular form, and a meta-analysis was performed on the treatment effects of AT on ADHD symptoms. Results: Fourteen studies involving 1185 patients evaluating the efficacy of AT for ADHD treatment were included in this review. Compared to conventional medicine alone, the meta-analysis indicated that AT as an add-on to conventional medicine has a positive effect on improving conduct problems, learning problems, hyperactivity–impulsivity, and hyperactivity symptoms in ADHD patients. Similarly, AT alone was found to improve learning problems, hyperactivity–impulsivity, and hyperactivity symptoms in ADHD patients and exhibited better total treatment efficacy than conventional medicine alone. No major adverse events were reported. The risk of bias of the included studies was generally concerning. Conclusions: Evidence on the effectiveness of AT for ADHD patients is currently too limited to provide recommendations for its usage. More studies with the proper methodology are needed for the validation of AT interventions in treating children with ADHD.

Messenger RNA (mRNA) vaccination was developed to mitigate the coronavirus disease 2019 pandemic. However, data on antibody kinetics and factors influencing these vaccines’ immunogenicity are limited. We conducted a prospective study on healthy young adults who received two doses of the mRNA-1273 vaccine at 28-day intervals. After each dose, adverse events were prospectively evaluated, and blood samples were collected. The correlation between humoral immune response and reactogenicity after vaccination was determined. In 177 participants (19–55 years), the geometric mean titers of anti-S IgG antibody were 178.07 and 4409.61 U/mL, while those of 50% neutralizing titers were 479.95 and 2851.67 U/mL four weeks after the first and second vaccine doses, respectively. Anti-S IgG antibody titers were not associated with local reactogenicity but were higher in participants who experienced systemic adverse events (headache and muscle pain). Antipyretic use was an independent predictive factor of a robust anti-SARS-CoV-2 antibody response after receiving both vaccine doses. Systemic reactogenicity after the first dose influenced antibody response after the second dose. In conclusion, mRNA-1273 induced a robust antibody response in healthy young adults. Antipyretic use did not decrease the anti-SARS-CoV-2 antibody response after mRNA-1273 vaccination.

Colorectal carcinoma invading the submucosa but not the muscularis propria (pT1) represents the earliest form of clinically relevant colorectal cancer in most patients. T1 colorectal cancer with synchronous liver metastasis is considered to be rare. We report a rare case of T1 colon cancer with synchronous liver metastasis not detected by preoperative imaging study. A 54-year-old male patient presented to our department for treatment of sigmoid colon cancer following an endoscopic submucosal dissection. Histopathological examination revealed the pedunculated mass was moderately differentiated adenocarcinoma without lymphovascular invasion and the depth of submucosal invasion was 2,000 μm, the resection margin was not involved. We performed a laparoscopic anterior resection with lymph node dissection. After the 3 months, the patient’s carcinoembryonic antigen level elevated from 1.4 to 7.26 ng/mL (normal level:

Background: Most women experiencing menopause have sought out traditional treatment options to relieve their symptoms. The aim of this study, which used a web-based survey, was to investigate perceptions of Korean medicine doctors (KMDs) on managing menopausal symptoms with herbal medicines. Methods: We developed and then sent a questionnaire via email to a total 497 KMDs in obstetrics and gynecology affiliated with the Society of Korean Medicine. The questionnaire consisted of three categories and a total of 26 items focusing on major menopausal symptoms, prescriptions, pattern identification, and background characteristics. Results: Out of the 497 KMDs, we received responses from 48 doctors, a response rate of 9.7%. The most common symptoms of menopausal disorder perceived by responded KMDs were hot flashes (22.9%), sleep disorders (18.2%), systemic fatigue (12.5%), and sweating (12.0%). The herbal medicines reported to be the most effective when treating patients with menopausal disorders were Jiawei shaoyao-san (12.5%), Jiawei guipi-decoction (11.8%). The responding KMDs recommended one to two months of treatment for female menopausal disorder, using two to three doses of herbal medicine per day in combination with traditional Korean medicine (KM) therapies such as acupuncture, moxibustion, cupping, and pharmacopuncture. Conclusion: The results of this survey may provide information about doctor’s perceptions on using herbal medicines to manage patient’s menopausal symptoms. Future studies should be done with a larger sample size to overcome the limitation of this study and to examine how KM is used for treating menopausal symptoms in clinical practice. Keywords: Menopausal symptoms, Herbal medicines, Web-based survey

Activated cdc42-associated kinase 1 (ACK1) is a well-known non-receptor tyrosine kinase that regulates cell proliferation and growth through activation of cellular signaling pathways, including mitogen-activated protein kinase (MAPK). However, the anti-HBV activity of ACK1 has not been elucidated. This study aimed to investigate the role of ACK1 in the HBV life cycle and the mechanism underlying the anti-HBV activity of ACK1. To examine the antiviral activity of ACK1, we established HepG2-ACK1 cells stably overexpressing ACK1. The HBV life cycle, including HBeAg/HBsAg secretion, HBV DNA/transcription, and enhancer activity, was analyzed in HepG2 and HepG2-ACK1 cells with HBV replication-competent HBV 1.2mer (HBV 1.2). Finally, the anti-HBV activity of ACK1 was examined in an HBV infection system. ACK1 suppressed HBV gene expression and transcription in HepG2 and HepG2-ACK1 cells. Furthermore, ACK1 inhibited HBV replication by decreasing viral enhancer activity. ACK1 exhibited its anti-HBV activity via activation of Erk1/2, which consequently downregulated the expression of HNF4α binding to HBV enhancers. Furthermore, hepatocyte growth factor (HGF) induced ACK1 expression at an early stage. Finally, ACK1 mediated the antiviral effect of HGF in the HBV infection system. These results indicated that ACK1 induced by HGF inhibited HBV replication at the transcriptional level by activating the MAPK-HNF signaling pathway. Our findings suggest that ACK1 is a potentially novel upstream molecule of MAPK-mediated anti-HBV activity.

Background and Objectives: ZBTB48 is a telomere-related protein that has been renamed telomeric zinc finger-associated protein (TZAP). It favorably binds to elongated telomeres to regulate their appropriate length. However, TZAP expression has not been investigated in hepatocellular carcinomas (HCC). Materials and Methods: The clinical significance of TZAP expression in 72 HCC was investigated. Additionally, its findings were supported by open big data and cancer cell lines. Results: TZAP expression level was not associated with the clinical parameters of HCC. TZAP expression induced a poorer survival result (overall survival, p = 0.020; disease-free survival, p = 0.012). TCGA data showed TZAP expression was more frequently found in HCCs with hepatitis C infection (p = 0.023). However, TCGA data revealed that TZAP expression did not predict HCC prognosis. In a cell line study, TZAP inhibition via siRNA suppressed PLC/PRF/5 cell growth; however, cell viability was increased in HepG2 cells. Conclusions: We presented the clinical and prognostic values of TZAP expression in HCC tissues and cancer cell lines. Additionally, the TCGA results also revealed a significant role for TZAP expression. TZAP expression may involve HCC progression and its prognosis.

This study aimed to evaluate the predictive performance of pre-existing well-validated hepatocellular carcinoma (HCC) prediction models, established in patients with HBV-related cirrhosis who started potent antiviral therapy (AVT). We retrospectively reviewed the cases of 1339 treatment-naïve patients with HBV-related cirrhosis who started AVT (median period, 56.8 months). The scores of the pre-existing HCC risk prediction models were calculated at the time of AVT initiation. HCC developed in 211 patients (15.1%), and the cumulative probability of HCC development at 5 years was 14.6%. Multivariate Cox regression analysis revealed that older age (adjusted hazard ratio [aHR], 1.023), lower platelet count (aHR, 0.997), lower serum albumin level (aHR, 0.578), and greater LS value (aHR, 1.012) were associated with HCC development. Harrell’s c-indices of the PAGE-B, modified PAGE-B, modified REACH-B, CAMD, aMAP, HCC-RESCUE, AASL-HCC, Toronto HCC Risk Index, PLAN-B, APA-B, CAGE-B, and SAGE-B models were suboptimal in patients with HBV-related cirrhosis, ranging from 0.565 to 0.667. Nevertheless, almost all patients were well stratified into low-, intermediate-, or high-risk groups according to each model (all log-rank p < 0.05), except for HCC-RESCUE (p = 0.080). Since all low-risk patients had cirrhosis at baseline, they had unneglectable cumulative incidence of HCC development (5-year incidence, 4.9–7.5%). Pre-existing risk prediction models for patients with chronic hepatitis B showed suboptimal predictive performances for the assessment of HCC development in patients with HBV-related cirrhosis.

Background: This study aimed to obtain the symptom, prescription and therapeutic patterns for the treatment of patients with menopausal syndrome in major Korean medicine (KM) hospitals. Methods: We used a retrospective chart review of climacteric disorder and postmenopausal syndrome patients by examining medical records (ICD-10, menopausal and female climacteric states: N95.1, Menopausal and perimenopausal disorder, unspecified: N95.9) from eight university KM hospitals in South Korea. Results: The main symptoms of 1,682 patients with menopausal disorders visiting 8 college-affiliated oriental medicine hospitals were hot flush, hyperhidrosis, fatigue, insomnia, and chest tightness. Guipi-tang (decoction), Siwu Guipi-tang (decoction), Qingxin Lianzi-yin (decoction), Jiawei Xiaoyao-san (powder) and Guipi Wendan-tang (decoction) were the most commonly prescribed herbal medicines for menopausal disorders. Patients were most often treated with a combination of herbal medicine and acupuncture. Conclusion: Our study shows that the current prescribed herbal medicines were used for treating menopausal disorders in Korean medicine hospitals. However, the objectivity of the efficacy assessment should be studied further.

Jaeumgeonbi-Tang (JGT), a traditional herbal medicine, has been used to treat dizziness and vertigo in Korea and China for hundreds of years. The purpose of this study was to evaluate the pharmacological properties of JGT in chronic subjective dizziness (CSD) patients. A randomized, double-blind, parallel-group and placebo-controlled trial was performed with a total of 50 CSD patients. The patients were randomly assigned to one of two groups: JGT or placebo (n = 25 for each). All participants received the treatment (placebo or JGT, 24 g/day) for 4 weeks. We analyzed the serum levels of oxidative stressors, antioxidants, and stress hormones. Serum levels of lipid peroxidation, but not nitric oxide, were significantly decreased in the JGT group. JGT not only prevented the decline of serum total glutathione contents and total antioxidant capacity, but it also increased superoxide dismutase and catalase activities. Serum levels of stress hormones including cortisol, adrenaline, and serotonin were notably normalized by JGT treatment, but noradrenaline levels were not affected. Regarding the safety and tolerability of JGT, we found no allergic, adverse, or side effects in any of the participants. JGT showed beneficial effects on CSD patients by improving redox status and balancing psycho-emotional stress hormones.

Background: Nocturnal crying is a common condition in which children intermittently or continuously cry and fuss during the night, at certain times or throughout the night. It is a common pediatric sleep disturbance for which medical assistance is highly sought by parents, and one of the non-pharmacologic treatments for nocturnal crying is pediatric acupuncture. This review aimed to review the literature about the effectiveness and safety of pediatric acupuncture for nocturnal crying.Methods: Literature searches were performed on PubMed, the Cochrane Controlled Register of Trials (CENTRAL), Allied and Complementary Medicine Database (AMED), Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Chinese Science and Technique Journals Database (VIP), OASIS, the Research Information Service System (RISS), and National Digital Science Library (NDSL) from the available date of inception until December 28, 2020. Two review authors independently screened the titles and abstracts of all relevant articles from the search to select eligible articles. All variants of clinical studies on acupuncture treatment for nocturnal crying, including case reports and case studies, were eligible. Data were independently extracted by two review authors using a standard data extraction form. Retrieved data are presented in a tabular form and narratively discussed.Results: We included 12 studies (10 case series and two case reports) with a total sample size of 2,324 children recruited from the hospital outpatient department. All of the included studies were conducted in mainland China and administered acupuncture as the sole intervention. For the primary outcome, the total efficacy rate of acupuncture treatment for nocturnal crying was reported as 100% in 9 studies, 95% in one study, 94% in another study, and 86% in the remaining study. For the secondary outcome, one study reported a 14% recurrence rate, whereas another study reported an 11% recurrence rate after treatment. There were no follow-ups in most of the studies. None of the studies reported possible adverse events. Most children recovered after one treatment. Generally, the acupoints that were most frequently selected were acupoints EM30 and PC9.Conclusions: This comprehensive review suggested that pediatric acupuncture may be an effective treatment for nocturnal crying, which could be worth investigating further.

In the assessment of second language oral communication, the video-call speaking test has received increasing attention as a test method with higher practicality than its in-person counterpart, but still with broad coverage of the test construct. Previous studies into video-call assessment have focussed on the individual (as opposed to paired or group) interactional format. The current study extends this line of research by focussing on paired speaking interactions, with a specific focus on the construct of interactional competence. A concurrent triangulation design was adopted with the use of both quantitative and qualitative data through recordings and scores of test performances, questionnaires, and focus groups. Findings indicate that video-call paired interactions in the assessment context of interest in this study are largely comparable to in-person interactions in terms of scores, with statistically small-effect size differences identified. Some differences in terms of turn-taking management, examiner, and test-taker perceptions were also identified. We argue for a more in-depth awareness of the characteristics of video-call speaking in its own right, which can inform both assessment and learning contexts.

Background/Aims The influence of hepatic steatosis (HS) on chronic hepatitis B (CHB) is unclear. We evaluated the influence of the degree of HS, assessed using the controlled attenuation parameter (CAP) of transient elastography (TE), on treatment outcomes in CHB patients initiated on antiviral therapy. Methods A total of 334 patients who were initiated on entecavir or tenofovir between 2007 and 2016 with available TE results were recruited. Results Of the total study population, 146 (43.7%) patients had HS (CAP > 238 dB/m). Three-hundred-three patients (90.7%) achieved complete virological response (CVR) (hepatitis B virus DNA

We present the case of a 71-year-old man who was diagnosed with amoebic encephalitis caused by Balamuthia mandrillaris. He had rheumatic arthritis for 30 years and had undergone continuous treatment with immunosuppressants. First, he complained of partial spasm from the left thigh to the left upper limb. Magnetic resonance imaging revealed multifocal enhancing nodules in the cortical and subcortical area of both cerebral hemispheres, which were suggestive of brain metastases. However, the patient developed fever with stuporous mentality and an open biopsy was performed immediately. Microscopically, numerous amoebic trophozoites, measuring 20 to 25 µm in size, with nuclei containing one to four nucleoli and some scattered cysts having a double-layered wall were noted in the background of hemorrhagic necrosis. Based on the microscopic findings, amoebic encephalitis caused by Balamuthia mandrillaris was diagnosed. The patient died on the 10th day after being admitted at the hospital. The diagnosis of amoebic encephalitis in the early stage is difficult for clinicians. Moreover, most cases undergo rapid deterioration, resulting in fatal consequences. In this report, we present the first case of B. mandrillaris amoebic encephalitis with fatal progression in a Korean patient.

Abstract Background There are large variations in prognosis among hepatocellular carcinoma (HCC) patients undergoing radiofrequency ablation (RFA). However, current staging or scoring systems hardly discriminate the outcome of HCC patients treated with RFA. Methods A total of 757 treatment‐naïve HCC patients undergoing RFA (derivation cohort) were analyzed to establish a nomogram for disease‐free survival (DFS) based on Cox proportional hazard regression model. Accuracy of the nomogram was assessed and compared with conventional staging or scoring systems. Furthermore, external validation was performed in an independent cohort including 208 patients (validation cohort). Results Tumor size, tumor number, alpha‐fetoprotein, prothrombin induced by vitamin K absence‐II, lymphocyte count, albumin, and presence of ascites were adopted to construct the prognostic nomogram from the derivation cohort. Calibration curves to predict probability of DFS at 3 and 5 years after RFA showed good agreements between the nomogram and actual observations. The concordance index of the present nomogram was 0.759 (95% confidence interval 0.728‐0.790), which was superior to those of conventional staging or scoring systems (range 0.505‐0.683, all P

Background: Cnidium officinale Makino (COM) has been used traditionally to treat female menstrual disorders, such as amenorrhea, hypomenorrhea and oligomenorrhea, by improving blood circulation. The present study aimed to investigate the alleviating effect of COM extracts on surgical injuryinduced ischemia in the hind-limb of mice. Methods: In this study, female C57BL/6 mice were ovariectomized, and the vessels of the hind-limb were excised after ligation by surgical silk (6–0). The mice were orally administered with COM (150 or 300 mg/kg/day) for 3 weeks, and the blood flow rate of hind-limbs was evaluated by using a laser Doppler system after hind-limb ischemic surgery in an in vivo study. Additionally, the migration and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated in an in vitro study. Results: The blood flow rate was synchronized to the nonischemic lesion of the hind-limb, and its elevation compared to the vehicle was observed at 14 and 21 days after hind-limb ischemic surgery in COM-treated groups. The number of capillaries increase in a dose-dependent manner in the COM-treated groups (150 and 300 mg/kg). In HUVECs, the activities of cell migration were significantly increased by 50 and 75 μg/mL for the COM-treated groups. In addition, the number of tubule branches and junctions was also increased by doses of COM (50 and/or 75 μg/mL). Conclusion: The results of our study suggested that the COM extract may have therapeutic application for the treatment of hind-limb ischemic damage, which is due to the improvement of the peripheral angiogenetic system. Keywords: Cnidium officinale Makino, Hind-limb ischemia, Angiogenesis, Blood flow

Background Neoadjuvant chemoradiation therapy (CRT) is a widely used preoperative treatment strategy for locally advanced rectal cancer (LARC). However, a few studies have evaluated the molecular changes caused by neoadjuvant CRT in these cancer tissues. Here, we aimed to investigate changes in immunotherapy-related immunogenic effects in response to preoperative CRT in LARC.Methods We analyzed 60 pairs of human LARC tissues before and after irradiation from three independent LARC cohorts, including a LARC patient RNA sequencing (RNA-seq) dataset from our cohort and GSE15781 and GSE94104 datasets.Results Gene ontology analysis showed that preoperative CRT significantly enriched the immune response in LARC tissues. Moreover, gene set enrichment analysis revealed six significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways associated with downregulated genes, including mismatch repair (MMR) genes, in LARC tissues after CRT in all three cohorts. Radiation also induced apoptosis and downregulated various MMR system-related genes in three colorectal cancer cells. One patient with LARC showed a change in microsatellite instability (MSI) status after CRT, as demonstrated by the loss of MMR protein and PCR for MSI. Moreover, CRT significantly increased tumor mutational burden in LARC tissues. CIBERSORT analysis revealed that the proportions of M2 macrophages and CD8 T cells were significantly increased after CRT in both the RNA-seq dataset and GSE94104. Notably, preoperative CRT increased various immune biomarker scores, such as the interferon-γ signature, the cytolytic activity and the immune signature.Conclusions Taken together, our findings demonstrated that neoadjuvant CRT modulated the immune-related characteristics of LARC, suggesting that neoadjuvant CRT may enhance the responsiveness of LARC to immunotherapy.

Background/Aims Untreated rupture of the thoracic aorta is associated with a high mortality rate. We aimed to review the clinical results of endovascular treatment for ruptured thoracic aortic disease. Methods We retrospectively reviewed data on 37 patients (mean age, 67.0 ± 15.18 years) treated for ruptured thoracic aortic disease from January 2005 to May 2016. The median follow-up duration was 308 days (interquartile range, 61 to 1,036.5). The primary end-point of the study was the composite of death, secondary intervention, endoleak, and major stroke/paraplegia after endovascular treatment. Results The etiologies of ruptured thoracic aortic disease were aortic dissection (n = 11, 29.7%), intramural hematoma (n = 7, 18.9%), thoracic aortic aneurysm (n = 14, 37.8%), and traumatic aortic transection (n = 5, 13.5%). Three patients died within 24 hours of thoracic endovascular aortic repair, and one showed type I endoleak. The technical success rate was 89.2% (33/37). The in-hospital mortality rate was 13.5% (5/37); no deaths occurred during follow-up. The composite outcome rate during follow-up was 37.8% (14/37), comprising death (n = 5, 13.5%), secondary intervention (n = 5, 13.5%), endoleak (n = 5, 13.5%), and major stroke/paraplegia (n = 3, 8.1%). Left subclavian artery revascularization and proximal landing zone were not associated with the composite outcome. Low mean arterial pressure (MAP; ≤ 60 mmHg, [hazard ratio, 13.018; 95% confidence interval, 2.435 to 69.583, p = 0.003]) was the most significant predictor and high transfusion requirement in the first 24 hours was associated with event-free survival (log rank p = 0.018). Conclusions Endovascular treatment achieves high technical success rates and acceptable clinical outcome. High transfusion volume and low MAP were associated with poor clinical outcomes.

Acquisition of acquired chemoresistance during treatment cycles in urothelial carcinoma of the bladder (UCB) is the major cause of death through enhancing the risk of cancer progression and metastasis. Elevated glucose flux through the abnormal upregulation of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) controls key signaling and metabolic pathways regulating diverse cancer cell phenotypes. This study showed that OGT expression levels in two human UCB cell models with acquired resistance to gemcitabine and paclitaxel were significantly upregulated compared with those in parental cells. Reducing hyper-O-GlcNAcylation by OGT knockdown (KD) markedly facilitated chemosensitivity to the corresponding chemotherapeutics in both cells, and combination treatment with OGT-KD showed more severe growth defects in chemoresistant sublines. We subsequently verified the suppressive effects of OGT-KD monotherapy on cell migration/invasion in vitro and xenograft tumor growth in vivo in chemoresistant UCB cells. Transcriptome analysis of these cells revealed 97 upregulated genes, which were enriched in multiple oncogenic pathways. Our final choice of suspected OGT glycosylation substrate was VCAN, S1PR3, PDGFRB, and PRKCG, the knockdown of which induced cell growth defects. These findings demonstrate the vital role of dysregulated OGT activity and hyper-O-GlcNAcylation in modulating treatment failure and tumor aggression in chemoresistant UCB.

Background: Medical observation period is a period of 14 days after any exposure to coronavirus disease 2019 (COVID-19) occurred. This review aimed to summarize and analyze the herbs and herbal formulae recommended by available guidelines. Methods: A total of 14 sources were searched for potential guidelines that provide herbal medicine treatment for the medical observation period of COVID-19. We summarized and analyzed the recommended herbal formulae and performed a network analysis to identify the relationship between herbs. Results: We found 9 guidelines that provide herbal formula for medical observation based on clinical manifestation. There are 12 herbal formulae with a total of 53 herbs recommended by the guidelines. The result of our network analysis showed that the herb Citri Reticulatae Pericarpium (Chen Pi) strongly paired with the herb Glycyrrhizae Radix et Rhizoma (Gan Cao). Conclusion: This review briefly summarized the usage of herbal medicine for the medical observation period of COVID-19 and may serve as a reference for future studies. More research is needed in the future to provide evidence on the usage of herbal medicine in various phases of COVID-10.

Background: Coronavirus disease 2019 (COVID-19) is pandemic and has caused illness to many people worldwide. This review aimed to summarize and analyze the herbal formulae provided by the guidelines for their pattern identifications (PIs) and compositions of herbs to treat patients with COVID-19. Methods: We searched 7 data sources for eligible traditional medicine guidelines up to March 6, 2020 and found a total of 28 traditional medicine guidelines that provide treatment measures for COVID-19. Results: Of the 28 guidelines, there were 26 government-issued Chinese guidelines and 2 Korean guidelines. After standardizing the terminology of the PIs and herbal formulae, there were 8 PIs and 23 herbal formulae for the mild stage, 11 PIs and 31 herbal formulae for the moderate stage, 8 PIs and 21 herbal formulae for the severe stage, and 6 PIs and 23 herbal formulae for the recovery stage in the Chinese guidelines. In the Korean guidelines, there were 4 PIs and 15 herbal formulae for the mild stage, 3 PIs and 3 herbal formulae for the severe stage, and 2 PIs and 2 herbal formulae for the recovery stage. In the frequency analysis of herbs, Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum, Ephedrae Herba, and Gypsum Fibrosum were found to be the herbs with the high frequency of usage in the Chinese guidelines. Conclusion: This review can be used as guidance for the traditional medicine treatment of COVID-19. Clinical evidence is needed in the future to evaluate the efficacy of traditional medicine.