The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Background: Limited data are available on hepatitis C virus (HCV) infection in persons who inject drugs (PWID) in South Korea. The present study aimed to investigate the seroprevalence of HCV antibodies, risk factors for HCV seropositivity, and HCV treatment status in PWID between January 2012 and May 2022. Methods: We retrospectively reviewed the medical records of 418 drug users who underwent HCV antibody testing in three hospitals caring for 90% of known PWID in South Korea, of whom 373 were PWID. Results: The HCV seroprevalence was 39.7% (148/373) in PWID vs. 6.7% (3/45) in noninjection drug users (P < 0.001). Age ≥ 40 years, hospital type (58.2% in the prison hospital vs. 34.0% in the private hospital), and enrollment year (68.2% in 2012–2014 vs. 30.0% in 2021–2022) were independently associated with HCV seropositivity. Among the HCVseropositive PWID, 90.5% (134/148) were diagnosed with HCV infection; however, only 6.8% (10/148) received HCV treatment. The hepatitis B virus surface antigen and human immunodeficiency virus antibody positivity were 4.0% (14/352) and 1.9% (6/317) in tested PWID, respectively. Conclusion The HCV seroprevalence in PWID was 39.7% with a very low treatment rate, which prompts active measures to test and treat PWID for HCV infection in South Korea.

BACKGROUND: We aimed to confirm the long-term effect of patellar nonresurfacing (patellar decompression) in preventing anterior knee pain after total knee arthroplasty (TKA) and to investigate the possible complications. METHODS: Among patients who underwent primary TKA after being diagnosed as having advanced osteoarthritis (Kellgren-Lawrence grade 4) at our institution from January 2004 to December 2010, 121 patients who were followed up for more than 7 years were included in this study. Patients who underwent TKA with and without patellar decompression were classified as the study group and control group, respectively. A clinical knee rating score was used to compare the postoperative clinical outcomes between groups. To identify complications after patellar decompression, simple radiographs (weight-bearing anteroposterior and lateral views, patella in 30° and 45° axial views, and whole scanogram) were taken during follow-up. RESULTS: There were no complications such as patellar fracture, osteonecrosis, and subluxation. At 2 years after surgery, the prevalence of anterior knee pain was 12.7% and 18.0% in the study group and control group, respectively (p = 0.42), and the number of patients with patellofemoral osteoarthritis grade II or over was lower in the study group (p = 0.03). At 7 years after surgery, the prevalence of anterior knee pain was 18.3% and 24.0% in the study group and control group, respectively (p = 0.45), and there was no statistically significant intergroup difference in the number of patients with patellofemoral osteoarthritis grade II or over (p = 0.11). CONCLUSIONS Patellar nonresurfacing TKA reduces anterior knee pain in the early postoperative period. The procedure can be considered a relatively safe option with fewer complications; however, its effectiveness appears to decrease over time.

Background and Objectives: The efficacy of radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) is well established. The standard approach to RFCA in AF is pulmonary vein isolation (PVI). However, a large proportion of patients experiences recurrence of atrial tachyarrhythmia. The purpose of this study is to find out whether the AI model can assess AF recurrence in patients who underwent PVI. Materials and methods: This study was a retrospective cohort study that enrolled consecutive patients who under‑ went catheter ablation for symptomatic, drug-refractory AF and PVI. We developed an AI algorithm to predict recur‑ rence of AF after PVI using patient demographics and three-dimensional (3D) reconstructed left atrium (LA) images. Results: We included 527 consecutive patients in the study. The overall mean LA diameter was 42.0 ± 6.8 mm, and the mean LA volume calculated using 3D reconstructed images was 151.1 ± 46.7 ml. During the follow-up period, atrial tachyarrhythmia recurred in 158 patients. The area under the curve (AUC) of the AI model based on a convolu‑ tional neural network (including 3D reconstruction images) was 0.61 (95% confidence interval [CI] 0.53–0.74) using the test dataset. The total test accuracy was 66.3% (57.0–75.6), and the sensitivity was 53.3% (34.8–71.9). The specificity was 73.2% (51.8–75.0), and the F1 score was 52.5% 34.5–66.7). Conclusion In this study, we developed an AI algorithm to predict recurrence of AF after catheter ablation of PVI using individual reconstructed LA images. This AI model was unable to predict recurrence of AF overwhelmingly;therefore, further large-scale study is needed.

PURPOSE: Lapatinib is a candidate drug for treatment of trastuzumab-resistant, human epidermal growth factor receptor 2 (HER2)–positive gastric cancer (GC). Unfortunately, lapatinib resistance renders this drug ineffective. The present study investigated the implication of forkhead box O1 (FOXO1) signaling in the acquired lapatinib resistance in HER2-positive GC cells. MATERIALS AND METHODS: Lapatinib-resistant GC cell lines (SNU-216 LR2-8) were generated in vitro by chronic exposure of lapatinib-sensitive, HER2-positive SNU-216 cells to lapatinib. SNU-216 LR cells with FOXO1 overexpression were generated by stable transfection of a constitutively active FOXO1 mutant (FOXO1A3). HER2 and MET in SNU-216 LR cells were downregulated using RNA interference. The sensitivity of GC cells to lapatinib and/or cisplatin was determined by crystal violet assay. In addition, Western blot analysis, luciferase reporter assay and reverse transcription–polymerase chain reaction were performed. RESULTS: SNU-216 LR cells showed upregulations of HER2 and MET, but downregulation of FOXO1 compared to parental SNU-216 cells. FOXO1 overexpression in SNU-216 LR cells significantly suppressed resistance to lapatinib and/or cisplatin. In addition, FOXO1 negatively controlled HER2 and MET at the transcriptional level and was negatively controlled by these molecules at the post-transcriptional level. A positive crosstalk was shown between HER2 and MET, each of which increased resistance to lapatinib and/or cisplatin. CONCLUSION: FOXO1 serves as an important linker between HER2 and MET signaling pathways through negative crosstalks and is a key regulator of the acquired lapatinib resistance in HER2-positive GC cells. These findings provide a rationale for establishing a novel treatment strategy to overcome lapatinib resistance in a subtype of GC patients.
Blotting, Western ; Cell Line ; Cisplatin ; Down-Regulation ; Drug Resistance ; Gentian Violet ; Humans ; In Vitro Techniques ; Luciferases ; Parents ; Receptor, Epidermal Growth Factor ; Receptor, ErbB-2 ; RNA Interference ; Stomach Neoplasms ; Transfection ; Up-Regulation

PURPOSE: To compare the clinical outcome of combined small incision lenticule extraction and collagen cross-linking (SMILE Xtra) with SMILE. METHODS: This study included 30 eyes from 15 patients who had undergone SMILE Xtra and a random sample of 30 eyes from 15 patients receiving SMILE alone during the same period. We obtained the following parameters from all patients: uncorrected (UDVA) and corrected distance visual acuity (CDVA), spherical equivalent (SE), efficacy and safety index, and corneal high-order aberrations. RESULTS: The SMILE Xtra group had higher preoperative SE and thinner central corneal and residual stromal bed thickness and optic zone diameter compared to the control group (p < 0.001). At 6 months, there was no significant difference in UDVA or CDVA between the two groups. The efficacy indices were 0.97 ± 0.16 and 1.05 ± 0.17 in the SMILE Xtra and control groups, respectively (p = 0.044), and there was no significant difference in safety index between the two groups during the follow-up period. Total corneal high-order aberrations numbered 2.59 ± 0.56 and 2.02 ± 0.41 in the SMILE Xtra and control groups, respectively (p < 0.001), and there was significant increase in spherical aberration and horizontal corneal aberration in both groups compared to preoperative results. Corneal haze was observed in 20% of eyes in the SMILE Xtra group, and no complication such as corneal ectasia was observed during the follow-up period. CONCLUSIONS: SMILE Xtra had good early clinical outcome compared to SMILE alone. It appears that SMILE Xtra can be a good modality when the cornea is thin or SE is high. However, postoperative corneal haze should be considered.
Collagen* ; Cornea ; Dilatation, Pathologic ; Follow-Up Studies ; Humans ; Visual Acuity

PURPOSE: To compare the clinical outcome of combined small incision lenticule extraction and collagen cross-linking (SMILE Xtra) with SMILE. METHODS: This study included 30 eyes from 15 patients who had undergone SMILE Xtra and a random sample of 30 eyes from 15 patients receiving SMILE alone during the same period. We obtained the following parameters from all patients: uncorrected (UDVA) and corrected distance visual acuity (CDVA), spherical equivalent (SE), efficacy and safety index, and corneal high-order aberrations. RESULTS: The SMILE Xtra group had higher preoperative SE and thinner central corneal and residual stromal bed thickness and optic zone diameter compared to the control group (p < 0.001). At 6 months, there was no significant difference in UDVA or CDVA between the two groups. The efficacy indices were 0.97 ± 0.16 and 1.05 ± 0.17 in the SMILE Xtra and control groups, respectively (p = 0.044), and there was no significant difference in safety index between the two groups during the follow-up period. Total corneal high-order aberrations numbered 2.59 ± 0.56 and 2.02 ± 0.41 in the SMILE Xtra and control groups, respectively (p < 0.001), and there was significant increase in spherical aberration and horizontal corneal aberration in both groups compared to preoperative results. Corneal haze was observed in 20% of eyes in the SMILE Xtra group, and no complication such as corneal ectasia was observed during the follow-up period. CONCLUSIONS: SMILE Xtra had good early clinical outcome compared to SMILE alone. It appears that SMILE Xtra can be a good modality when the cornea is thin or SE is high. However, postoperative corneal haze should be considered.
Collagen* ; Cornea ; Dilatation, Pathologic ; Follow-Up Studies ; Humans ; Visual Acuity

OBJECTIVE: To investigate the clinical feasibility of a newly developed, portable, gait assistive robot (WA-H, ‘walking assist for hemiplegia’) for improving the balance function of patients with stroke-induced hemiplegia. METHODS: Thirteen patients underwent 12 weeks of gait training on the treadmill while wearing WA-H for 30 minutes per day, 4 days a week. Patients' balance function was evaluated by the Berg Balance Scale (BBS), Fugl-Meyer Assessment Scale (FMAS), Timed Up and Go Test (TUGT), and Short Physical Performance Battery (SPPB) before and after 6 and 12 weeks of training. RESULTS: There were no serious complications or clinical difficulties during gait training with WA-H. In three categories of BBS, TUGT, and the balance scale of SPPB, there was a statistically significant improvement at the 6th week and 12th week of gait training with WA-H. In the subscale of balance function of FMAS, there was statistically significant improvement only at the 12th week. CONCLUSION: Gait training using WA-H demonstrated a beneficial effect on balance function in patients with hemiplegia without a safety issue.
Gait* ; Hemiplegia ; Humans ; Rehabilitation* ; Robotics ; Stroke

OBJECTIVES: This study analyzed the incidence and characteristics of in-hospital cardiac arrest (IHCA) in Korea based on a sample group of patients that is representative of the population. METHODS: The incidence of IHCA in adults was extracted from HIRA-NIS-2009, a sample of all patients using medical services in Korea. IHCA patients were analyzed according to gender, age, type of medical institute, and classification under the 6th revision of the Korean Standard Classification of Diseases (KCD-6). In addition, to assess the differences arising from the size of medical institutes, the IHCA incidence was analyzed in relation to the number of inpatient beds. RESULTS: Based on the sample data, the total incidence of IHCA in Korea was found to be 2.46 per 1,000 admissions (95% confidence interval [CI], 2.37–2.55). A higher incidence was found among men at 3.18 (95% CI, 3.03–3.33), compared to women at 1.84 (95% CI, 1.74–1.94). The incidence of IHCA was also higher in hospitals that had more than 600 inpatients beds at 5.40 (95% CI, 5.16–5.66) in comparison to those that had less than 600 inpatients beds at 4.09 (95% CI, 3.76–4.36) (p < 0.001). By primary disease, the incidence was the highest for infectious diseases. CONCLUSIONS: We demonstrated that the IHCA incidence based on gender, age, diagnostic group, and number of beds could be analyzed using the insurance claim data from a national representative sample.
Academies and Institutes ; Adult* ; Cardiopulmonary Resuscitation ; Classification ; Communicable Diseases ; Epidemiology ; Female ; Heart Arrest* ; Humans ; Incidence* ; Inpatients ; Insurance ; Korea* ; Male ; National Health Programs

BACKGROUND/AIMS: Recently, the incidence of nursing home-acquired pneumonia (NHAP) has been increasing and is now the leading cause of death among nursing home residents. This study was performed to identify risk factors associated with NHAP mortality, focusing on facility characteristics. METHODS: Data on all patients > or = 70 years of age admitted with newly diagnosed pneumonia were reviewed. To compare the quality of care in nursing facilities, the following three groups were defined: patients who acquired pneumonia in the community, care homes, and care hospitals. In these patients, 90-day mortality was compared. RESULTS: Survival analyses were performed in 282 patients with pneumonia. In the analyses, 90-day mortality was higher in patients in care homes (12.2%, 40.3%, and 19.6% in community, care homes, and care hospitals, respectively). Among the 118 NHAP patients, residence in a care home, structural lung diseases, treatment with inappropriate antimicrobial agents for accompanying infections, and a high pneumonia severity index score were risk factors associated with higher 90-day mortality. However, infection by potentially drug-resistant pathogens was not important. CONCLUSIONS: Unfavorable institutional factors in care homes are important prognostic factors for NHAP.
Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Cause of Death ; Cross Infection/diagnosis/drug therapy/microbiology/*mortality ; Female ; *Homes for the Aged ; *Hospitals ; Humans ; Inappropriate Prescribing ; Kaplan-Meier Estimate ; Male ; *Nursing Homes ; Pneumonia, Bacterial/diagnosis/drug therapy/microbiology/*mortality ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome