Structural Modification and Characteristics of Lappaconitine Alkaloid for the Discovery of Bioactive Components by Hypervalent Iodine Reagent.

Lappaconitine, a diterpene alkaloid isolated from Aconitum sinomontanum Nakai, exhibits a wide range of biological activities, making it a promising candidate for the development of novel derivatives with therapeutic potential. In our research, we executed a two-step transformation via oxidative cleavage of lappaconitine's vicinal diol using the hypervalent iodine reagent PhI(OAc)2, followed by strong alkaline hydrolysis. This approach yielded four new unanticipated compounds, whose structures were identified by spectroscopic methods and/or X-ray crystallography. Thus, we proposed plausible reaction mechanisms for their formations and particularly investigated the remarkable diastereoselectivity for the formation of single stereoisomer 8 observed during the alkaline hydrolysis step. Among them, compound 8 (code name: QG3030) demonstrated both enhanced osteogenic differentiation of human mesenchymal stem cells and significant osteogenic effect in an ovariectomized rat model with no acute oral toxicity.

Using Platelet-Rich Fibrin to Remove Graphite Tattoos May Yield Excellent Long-Term Result.

Graphite tattoos are rarely reported because they are mainly caused by an accidental injury or habits during childhood that cause a pencil to penetrate the oral mucosa. Unlike other pigmentations, it stains layers that are deeper than the subepithelial and mucosal layers, and in most cases, it takes the form of a grayish black macule. This case report describes depigmentation with the denudation technique that was followed by a novel approach of using platelet-rich fibrin to cover exposed bone. A 41-year-old male patient presented with an aesthetic complaint from a grayish black staining on the labial gingiva near the maxillary central and lateral incisors. The lesion was diagnosed as a graphite tattoo due to the patient's history of sticking his gum with pencils when he was young. The entire pigmented gingiva was surgically removed and covered with two layers of PRF membrane to protect the exposed bone surface and provide an extracellular matrix for migration of gingival fibroblasts. Healing patterns were observed at 1, 2, 4, and 8 weeks, and satisfactory clinical and aesthetic results were obtained. Creeping attachment was observed at 8 years postop, and there was no recurrence for a long-term period of 13 years.

Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study.

Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.

Predictors of Choledocholithiasis in Cholecystectomy Patients and Their Cutoff Values and Prediction Model in Korea in Comparison with the 2019 ASGE Guidelines.

Background/Aims: : In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) established clinical predictors for choledocholithiasis. Our study was designed to evaluate these predictors within the Korean clinical context, establish cutoff values, and develop a predictive model. Methods: : This retrospective study analyzed patients who underwent laparoscopic cholecystectomy. The relationships between choledocholithiasis and predictors including age, blood tests, and imaging findings were assessed through univariate and multivariate logistic regression analyses. We established Korean cutoff values for these predictors and developed a scoring system for choledocholithiasis using a multivariate logistic regression. The performance of this scoring system was then compared with that of the 2019 ASGE guidelines through a receiver operating characteristic curve. Results: : We established Korean cutoff values for age (>70 years), alanine aminotransferase (>26.5 U/L), aspartate aminotransferase (>28.5 U/L), gamma-glutamyl transferase (GGT; >82.5 U/L), alkaline phosphatase (ALP; >77.5 U/L), and total bilirubin (>0.95 mg/dL). In the multivariate analysis, only age >70 years, GGT >77.5 U/L, ALP >77.5 U/L, and common bile duct dilatation remained significant. We then developed a new Korean risk stratification model from the multivariate analysis, with an area under the curve of 0.777 (95% confidence interval, 0.75 to 0.81). Our model was stratified into the low-risk, intermediate-risk, and high-risk groups with the scores being <1.0, 1.0-5.5, and >5.5, respectively. Conclusions: : Predictors of choledocholithiasis in cholecystectomy patients and their cutoff values in Korean should be adjusted and further studies are needed to develop appropriate guidelines.

Programmed Death 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Gene Expression in Peripheral Blood Mononuclear Cells Can Serve as Prognostic Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive form of liver cancer with poor prognosis. The lack of reliable biomarkers for early detection and accurate diagnosis and prognosis poses a significant challenge to its effective clinical management. In this study, we investigated the diagnostic and prognostic potential of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in peripheral blood mononuclear cells (PBMCs) in HCC. PD-1 and CTLA-4 gene expression was analyzed comparatively using PBMCs collected from HCC patients and healthy individuals. The results revealed higher PD-1 gene expression levels in patients with multifocal tumors, lymphatic invasion, or distant metastasis than those in their control counterparts. However, conventional serum biomarkers of liver function do not exhibit similar correlations. In conclusion, PD-1 gene expression is associated with OS and PFS and CTLA-4 gene expression is associated with OS, whereas the serum biomarkers analyzed in this study show no significant correlation with survival in HCC. Hence, PD-1 and CTLA-4 expressed in PBMCs are considered potential prognostic biomarkers for patients with HCC that can facilitate prediction of malignancy, response to currently available HCC treatments, and overall survival.

Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Da Vinci robot-assisted endoscopic full-thickness gastric resection with regional lymph node dissection using a 3D near-infrared video system: a single-center 5-year clinical outcome.

BACKGROUND: Endoscopic full-thickness gastric resection (EFTGR) with regional lymph node dissection (LND) has been used for early gastric cancer (EGC) exceeding the indications for endoscopic submucosal dissection (ESD). The extent of the dissected lymph nodes is crucial. A 3D near-infrared (NIR) video robot system significantly enhances visualization of the lymphatic system. However, this system has not been used in EFTGR with LND. Thus, this study assessed the benefits of the 3D NIR video robot system in a clinical setting. METHODS: Between February 2015 and September 2018, 24 patients with EGC exceeding the indications for ESD were treated with EFTGR and LND using a 3D NIR video system with the da Vinci surgical robot. Indocyanine green (ICG) was injected endoscopically around the tumor, and basin node (BN) dissection around the nodes was examined using the 3D NIR video system of the da Vinci Si surgical robot. Subsequently, robot-assisted EFTGR was performed. The primary outcome was the 5-year survival rate. RESULT: During a 5-year follow-up of all 24 patients, an 80-year-old patient with an ulcer and T2 invasion was lost to follow-up. Among the remaining 23 patients, no mortality or recurrence was observed. CONCLUSION: No metastasis or mortality occurred using the da Vinci robot-assisted EFTGR with LLND and a 3D NIR video system for patients who required radical gastrectomy for EGC in over 5 years. Hence, this may be a safe and effective method for radical gastrectomy; further studies are required confirming its effectiveness.

Endoscopic resection and laparoscopic lymph node dissection for early gastric cancer beyond conventional endoscopic treatment indications: a 10-year outcome study.

BACKGROUND: Endoscopic full-thickness gastric resection (EFTGR) with laparoscopic regional lymph node dissection (LLND) and endoscopic submucosal dissection (ESD) with LLND have been investigated as treatment options for early gastric cancer beyond the absolute indications for ESD. However, comparative studies on the long-term outcomes of these procedures are lacking. This study aimed to analyze and compare the 10-year outcomes of both procedures in a real clinical setting. METHODS: Between January 2009 and December 2013, 28 and 37 patients diagnosed with EGC beyond the absolute indications for ESD were treated with EFTGR with LLND and ESD with LLND, respectively. In both procedures, the dye was injected into the tumor. However, after injection and LLND, EFTGR was performed immediately in the EFTGR with LLND group, whereas LLND was followed by ESD in the ESD with LLND group. The primary endpoint was the 10-year survival rate. RESULTS: The EFTGR with LLND group had one case of local recurrence (3.6%) and mortality (3.6%) each, while the ESD with LLND group had none (0.0% for both); however, the differences were not statistically significant (P = 0.247 for each). Furthermore, there was no significant difference in complications such as ischemia and anastomosis leakage between the groups (P = 0.247). CONCLUSIONS: When the procedures were properly applied, EFTGR with LLND and ESD with LLND did not increase the 10-year mortality in patients with EGC beyond the absolute ESD indications compared with conventional radical gastrectomy.

Delayed Implant Fixture Displacement into the Maxillary Sinus Five Years Post-Loading: Unraveling the Causes - A Case Report.

Reports of implant fixtures dislocating into the maxillary sinus during sinus graft procedures are well-documented. However, cases of fixtures migrating into the sinus long after placement have yet to be reported. This case report details the surgical extraction of a displaced screw and cement-retained prosthesis, including a fixture and its abutment, from the maxillary sinus after a minimum of 5 years under functional load. The extracted implant was subsequently examined using scanning electron microscopy and energy-dispersive x-ray spectroscopy. We found that the migration commenced with peri-implantitis surrounding the implant, replacing the second molar. This was accompanied by a loss of cement from the crown on this implant and concurrent loosening of the abutment screw on the implant, replacing the first molar. We hypothesize that the inability of the bony tissue surrounding the second molar implant to withstand occlusal forces resulted in forming a bony sequestrum. This process ultimately precipitated the migration of the fixture, along with its abutment and adjacent necrotic bone, into the sinus cavity.

Chronic active EBV infection: the experience of the Samsung Medical Center in South Korea / Infección crónica activa por virus de Epstein-Barr: experiencia del Centro Médico Samsung en Corea del Sur

Abstract Background: Chronic active EBV infection (CAEBV) of T-cell or NK-cell type is an EBV+ polyclonal, oligoclonal or often monoclonal lymphoproliferative disorder (LPD) recognized as representing the spectrum of EBV-associated T-cell and NK-cell LPD with different clinical presentations; one systemic and two cutaneous disorders including hydroa vacciniforme-like T-cell LPD and mosquito bite hypersensitivity. The systemic form of the disease is characterized by fever, persistent hepatitis, hepatosplenomegaly and lymphadenopathy, which shows varying degrees of clinical severity depending on the immune response of the host and the EBV viral load. Case reports: We described the clinicopathological findings of two children with CAEBV with a brief review of the literature. Conclusions: Recognition of the disease is important for adequate management of the patient. EBV analysis should be included in the principal diagnostic tests for febrile children.

Resumen Introducción: La infección crónica activa (CA) de células T o células tipo NK por virus de Epstein-Barr (VEB) es un desorden linfoproliferativo (DLP) VEB+ policlonal, oligoclonal o, frecuentemente, monoclonal reconocido como representación del espectro del DLP de células T y células NK asociado con VEB que tiene diversas presentaciones clínicas: un padecimiento sistémico y dos cutáneos que incluyen el DLP de células T que semeja hidroa vacciniforme y la hipersensibilidad por picadura de mosquito. Los síntomas de la enfermedad sistémica incluyen fiebre, hepatitis persistente, hepatoesplenomegalia y linfadenopatías que muestran diferente grado de severidad clínica, dependiendo de la respuesta inmune del hospedero y de la carga viral del VEB. Casos clínicos: Se describen los hallazgos clínico-patológicos de dos niños con CAVEB y una breve revisión de la literatura. Conclusiones: Es importante reconocer esta enfermedad para proporcionar el manejo adecuado al paciente. El análisis de VEB debería incluirse como una de las principales pruebas diagnósticas en niños con fiebre.