Background/Aims: The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells. Methods: Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors. The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively. Results: We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function. Conclusions Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background/Aims: Patients with active cancer frequently develop venous thromboembolism (VTE). However, there is little data about VTE in patients with advanced cholangiocarcinoma (CCA). Therefore, we investigated the clinical significance of VTE in patients with advanced CCA. Methods: We analyzed the data of a total of 332 unresectable CCA patients diagnosed between 2010 and 2020 in this retrospective study. We investigated the incidence and risk factors for VTE, and its effect on survival in patients with advanced CCA. Results: During a median follow-up of 11.6 months, 118 patients (35.5%) developed VTE. The cumulative incidence of VTE was 22.4% (95% confidence interval [CI], 0.18 to 0.27) at 3 months and 32.8% (95% CI, 0.27 to 0.38) at 12 months. Major vessel invasion was an independent risk factor for VTE (hazard ratio, 2.88; 95% CI, 1.92 to 4.31; p<0.001). Patients who developed VTE during follow-up had shorter overall survival than patients who did not (11.50 months vs 15.83 months, p=0.005). In multivariable analysis, VTE (hazard ratio, 1.58; 95% CI, 1.23 to 2.02;p<0.001) was associated with poor overall survival. Conclusions Major vessel invasion is related to the occurrence of VTE in advanced CCA. The development of VTE significantly decreases the overall survival and is an important unfavorable prognostic factor for survival.

Background: This study aimed to analyze the accuracy of the output of three-dimensional (3D) customized surgical guides and titanium implants in a rabbit model, and of mandibulectomy, reconstructive surgery, and surgical outcome; additionally, the correlation between surgical accuracy and surgical outcomes, including the differences in surgical outcome according to surgical accuracy, was analyzed. Results: The output of implants was accurately implemented within the error range (− 0.03–0.03 mm), and the surgical accuracy varied depending on the measured area (range − 0.4–1.1 mm). Regarding surgical outcomes, anglebetween the mandibular lower borders showed the most sensitive results and distance between the lingual cusps of the first molars represented the most accurate outcomes. A significant correlation was noted between surgical accuracy in the anteroposterior length of the upper borders pre- and postoperatively and the angle between themandibular lower borders (regression coefficient = 0.491, p = 0.028). In the group wherein surgery was performed more accurately, the angle between the mandibular lower borders was reproduced more accurately (p = 0.021). Aselective laser melting machine accurately printed the implants as designed. Considering the positive correlation among surgical accuracy in the mandibular upper borders, angle between the mandibular lower borders, and more accurately reproduced angle between the mandibular lower borders, the angle between the mandibular lower borders is considered a good indicator for evaluating the outcomes of reconstructive surgery. Conclusion To reduce errors in surgical outcomes, it is necessary to devise a positioner for the surgical guide and design a 3D surgical guide to constantly maintain the direction of bone resection. A fixed area considering the concept of three-point fixation should be selected for stable positioning of the implant; in some cases, bilateral cortical bone fixation should be considered. The angle between the mandibular lower borders is a sensitive indicator for evaluating the outcomes of reconstructive surgery.

Background/Aims: The combinatorial effects of prophylactic methods for postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) in patients with risk factors remain unclear. In this network meta-analysis, we compared the efficacy of various prophylactic strategies to decrease the risk of PEP among patients with risk factors. Methods: A systematic review was performed to identify randomized controlled trials from PubMed, Embase, and the Cochrane Library through July 2021. We used frequentist network meta-analysis to compare the rates of PEP among patients who received prophylactic treatments as follows: class A, rectal nonsteroidal anti-inflammatory drugs; class B, prophylactic pancreatic stent; class C, aggressive hydration; or control, no prophylaxis or active control. We selected those studies that included patients with risk factors for PEP. Results: We identified 19 trials, comprising 4,328 participants. Class ABC (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.03 to 0.24), class AC (OR, 0.10; 95% CI, 0.02 to 0.47), class AB (OR, 0.12; 95% CI, 0.05 to 0.26), class BC (OR, 0.13; 95% CI, 0.04 to 0.41), class A (OR, 0.16; 95% CI, 0.05 to 0.50), and class B (OR, 0.26; 95% CI, 0.14 to 0.46), were associated with a reduced risk of PEP as compared to that of the control. The most effective prophylaxis was ABC (0.87), followed by AC (0.68), AB (0.65), BC (0.56), A (0.49), and B (0.24) according to P-score. Conclusions The results of this network meta-analysis suggest that the more prophylactic methods are employed, the better the outcomes. It appears that for patients with risk factors, we need to prevent PEP through the use of these well proven combination strategies.

Peripheral scalp T-cell lymphoma is a very rare disease. We report a case of a 22-year-old man who presented an indolent large scalp mass in the right frontal scalp region. The patient’s physical examination demonstrated no palpable mass in the chest, abdomen, and extremities. The brain CT revealed a high-density large scalp mass of the subgaleal layer in the right frontal and a small scalp mass of the subgaleal layer in the left frontal. The brain MRI showed multifocal enhancing masses in the bilateral dura, the subgaleal layer of the scalp, and the skull. The patient underwent removal of the tumor found in the right frontal scalp. The histologic diagnosis was peripheral T-cell lymphoma. Bone marrow aspiration showed the involvement of T-cell lymphoma. The patient received chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP protocol) for 3 cycles. The patient was discharged without neurological deficit. The patient showed no evidence of recurrence 15 months after surgery. We report a rare case of peripheral T-cell lymphoma mimicking benign scalp tumors.

Objective: We aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer’s disease study (BICWALZS) participants. Methods: A total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants. Results: The mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer’s dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer’s disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea. Conclusion The BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.

Objective: : Cervical surgery in patients with cervical spondylotic myelopathy (CSM) and cerebral palsy (CP) is challenging owing to the complexities of the deformity. We assessed factors affecting postoperative complications and outcomes after CSM surgery in patients with CP. Methods: : Thirty-five consecutive patients with CP and CSM who underwent cervical operations between January 2006 and January 2014 were matched to 35 non-cerebral palsy (NCP) control patients. Postoperative complications and radiologic outcomes were compared between the groups. In the CP group, the Japanese Orthopaedic Association score; Oswestry neck disability index; modified Barthel index; and values for the grip and pinch, Box and Block, and Jebsen-Taylor hand function tests were obtained preand postoperatively and compared between those with and without postoperative complications. Results: : Sixteen patients (16/35%) in the CP group and seven (7/35%) in the NCP group (p=0.021) had postoperative complications. Adjacent segment degeneration (p=0.021), postoperative motor weakness (p=0.037), and revisions (p=0.003) were significantly more frequent in the CP group than in the NCP group; however, instrument-related complications were not significantly higher in the CP group (7/35 vs. 5/35, p=0.280). The number of preoperative fixed cervical deformities were significantly higher in CP with postoperative complications (5/16 vs. 1/19, p=0.037). In the CP group, clinical outcomes were almost similar between those with and without postoperative complications. Conclusion : The occurrence of complications during the follow-up period was high in patients with CP. However, postoperative complications did not significantly affect clinical outcomes.

Purpose: Thioacetamide (TAA) produces reactive oxygen species (ROS) in the liver, and the generated ROS induces liver injury through inflammatory reactions. The current study was undertaken to investigate the hepatoprotective effect of Artemisiae Capillaris Herba water extract (AC), imparted via its antioxidant activity, in an animal model of TAA-induced liver injury. Methods: Animal experiments were conducted in 5 groups: normal, control (TAA 200 mg/kg), SM (TAA 200 mg/kg + silymarin 100 mg/kg), ACL (TAA 200 mg/kg + AC 100 mg/kg), ACH (TAA 200 mg/kg + AC 200mg/kg). TAA (intraperitoneal) and treatment compounds (per oral) were administered for 3 days. Serum levels of ammonia concentration and myeloperoxidase (MPO) activity were subsequently measured. Liver tissues were subjected to western blot analysis for measuring the oxidative stress (NADPH oxidase), anti-oxidative activity (Nrf2, heme oxygenase-1 [HO-1], superoxide dismutase [SOD], catalase, and GPx-1/2), tissue inhibitors of metalloproteinase (TIMP)-1, and matrix metalloproteinases (MMPs) protein expressions. Results: Serum ammonia levels and MPO activity were significantly increased in the TAAinduced control group, whereas groups administered AC treatment showed markedly reduced levels. Western blot analysis revealed significantly increased NOX2 and p22phox expressions, (oxidative stress-related factors) in the TAA-induced control group. These levels were determined to be significantly decreased after AC exposure. Moreover, antioxidantrelated factors including Nrf2, HO-1, SOD, catalase, and GPx-1/2 were significantly decreased in the control group and increased in the AC treated groups. In addition, MMP expressions were significantly suppressed in the AC treatment group due to increased levels of TIMP-1. Conclusion Taken together, these data indicate that exposure to AC reduces the oxidative stress by inhibiting the expression of NADPH oxidase (NOX2 and p22phox ) through the Nrf2 signaling pathway. We therefore propose the potential of AC for the prevention and treatment of TAA-induced liver injury.