Background: Genetic alterations play a pivotal role in multiple myeloma (MM) development and therapeutic resistance. Traditionally, the genetic profiling of MM requires invasive bone marrow (BM) procedures; however, these procedures are associated with patient discomfort and cannot fully capture the spatial and temporal heterogeneity of the disease.Therefore, we investigated the clinical implications of liquid biopsy using targeted deep sequencing. Methods: We analyzed the genetic profiles of circulating tumor DNA (ctDNA) by targeted deep sequencing from 102 patients, including those with monoclonal gammopathy of undetermined significance (MGUS, N = 7), smoldering MM (N = 6), and symptomatic MM (N = 89). Results: The number of ctDNA mutations increased with disease progression from MGUS to MM, with averages of 1.0 mutations in MGUS, 1.8 mutations in smoldering MM, and 1.9 mutations in MM, respectively. Shared mutations between BM and ctDNA were more prevalent in MM (68.9%) than in MGUS (25.0%). RAS/RAF and TP53 mutations were significantly enriched in MM ctDNA. Specific mutations were associated with clinical features in patients with MM: hypercalcemia and TET2 (P = 0.006), renal insufficiency and NRAS (P = 0.012), paramedullary myeloma and TP53(P = 0.02), and extramedullary myeloma and NRAS (P = 0.007). TET2 mutations significantly affected 2-yr progression-free survival (hazard ratio = 7.11, P = 0.003). Serial ctDNA profiling accurately predicted treatment response in patients with MM. Conclusions Our findings highlight the potential of liquid biopsy for understanding MM progression and prognosis utilizing a minimally invasive approach, paving the way for its integration into personalized treatment strategies and real-time disease monitoring.

Mangiferin is a kind of natural xanthone glycosides and is known to have various pharmacological activities. However, since the beneficial efficacy of this compound has not been reported in retinal pigment epithelial (RPE) cells, this study aimed to evaluate whether mangiferin could protect human RPE ARPE-19 cells from oxidative injury mimicked by hydrogen peroxide (H 2O 2). The results showed that mangiferin attenuated H 2O 2-induced cell viability reduction and DNA damage, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione (GSH). Mangiferin also antagonized H 2O 2-induced inhibition of the expression and activity of antioxidant enzymes such as manganese superoxide dismutase and GSH peroxidase, which was associated with inhibition of mitochondrial ROS production. In addition, mangiferin protected ARPE-19 cells from H 2O 2-induced apoptosis by increasing the Bcl-2/Bax ratio, decreasing caspase-3 activation, and blocking poly(ADP-ribose) polymerase cleavage. Moreover, mangiferin suppressed the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Furthermore, mangiferin increased the expression and activity of heme oxygenase-1 (HO-1) and nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the inhibition of ROS production, cytoprotective and anti-apoptotic effects of mangiferin were significantly attenuated by the HO-1 inhibitor, indicating that mangiferin promoted Nrf2-mediated HO-1 activity to prevent ARPE-19 cells from oxidative injury. The results of this study suggest that mangiferin, as an Nrf2 activator, has potent ROS scavenging activity and may have the potential to protect oxidative stress-mediated ocular diseases.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Methods: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. Results: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). Conclusion Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Background: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Methods: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. Results: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). Conclusion Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

PURPOSE: Brown tumor is a tumor-like disease that can occur as a linked disease of hyperparathyroidism which can causes osteoporosis, osteitis fibrosa cystica, pathologic fractures. Brown tumor has been reported as a case report, but there is no comprehensive report on the exact diagnosis and principle of management for osseous lesion. The purpose of this study is to report the treatment and results of osseous lesions through 5 cases. MATERIALS AND METHODS: From February 2004 to May 2015, five cases of Brown tumor were diagnosed in Chosun University Hospital and Chonnam National University Hospital orthopedic department. Medical records and radiographs were reviewed retrospectively. Parathyroid tumors were surgically removed, and surgical treatment and observation were performed for orthopedic osseous lesions. RESULTS: The mean length of the long axis of the symptomatic osseous lesion was 6.2 cm (4.5–9.0 cm). An average of 7.6 (range, 3 to 14) of high uptake osseous lesion showed in whole body bone scan. The absolute value, T-score and Z-score of the vertebrae and proximal femur were adequate for diagnosis of osteoporosis using dual energy X-ray absorptiometry bone mineral density at diagnosis and recovered to normal at the last follow-up. In laboratory tests, serum concentrations of total calcium, ionized calcium, inorganic phosphorus, serum alkaline phosphatase, and parathyroid hormone were helpful to diagnosis and normalized upon successful removal of parathyroid adenoma or cancer. CONCLUSION For accurate diagnosis of Brown tumor, it should be accompanied by systemic examination as well as clinical symptoms, laboratory tests and radiologic examination for osseous lesions. And a good prognosis can be expected if the hyperparathyroidism is treated together with the comprehensive treatment of osseous lesions.

PURPOSE: Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) are associated with a decreased incidence of new-onset diabetes mellitus (NODM). The aim of this study was to compare the protective effect of ACEI versus ARBs on NODM in an Asian population. MATERIALS AND METHODS: We investigated a total of 2817 patients who did not have diabetes mellitus from January 2004 to September 2009. To adjust for potential confounders, a propensity score matched (PSM) analysis was performed using a logistic regression model. The primary end-point was the cumulative incidence of NODM, which was defined as having a fasting blood glucose > or =126 mg/dL or HbA1c > or =6.5%. Multivariable cox-regression analysis was performed to determine the impact of ACEI versus ARB on the incidence of NODM. RESULTS: Mean follow-up duration was 1839+/-1019 days in all groups before baseline adjustment and 1864+/-1034 days in the PSM group. After PSM (C-statistics=0.731), a total 1024 patients (ACEI group, n=512 and ARB group, n=512) were enrolled for analysis and baseline characteristics were well balanced. After PSM, the cumulative incidence of NODM at 3 years was lower in the ACEI group than the ARB group (2.1% vs. 5.0%, p=0.012). In multivariate analysis, ACEI vs. ARB was an independent predictor of the lower incidence for NODM (odd ratio 0.37, confidence interval 0.17-0.79, p=0.010). CONCLUSION: In the present study, compared with ARB, chronic ACEI administration appeared to be associated with a lower incidence of NODM in a series of Asian cardiovascular patients.
Adult ; Aged ; Angiotensin Receptor Antagonists/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/*therapeutic use ; Asian Continental Ancestry Group/*statistics & numerical data ; Blood Glucose/analysis ; Diabetes Mellitus/*diagnosis/*epidemiology ; Dose-Response Relationship, Drug ; Drug Monitoring/methods ; Female ; Follow-Up Studies ; Humans ; Hypertension/*drug therapy ; Incidence ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Propensity Score ; Republic of Korea/epidemiology ; Risk Factors

Partial or complete absence of the posterior arch of the atlas is a well-documented anomaly but a relatively rare condition. This condition is usually asymptomatic so most are diagnosed incidentally. There have been a few documented cases of congenital defects of the posterior arch of the atlas combined with atlantoaxial subluxation. We report a very rare case of congenital anomaly of the atlas combined with atlantoaxial subluxation, that can be misdiagnosed as posterior arch fracture.
Adult ; Cervical Atlas/*abnormalities ; Diagnosis, Differential ; Female ; Humans ; Spinal Diseases/*diagnosis

OBJECTIVE: To adapt and standardize the Motor-Free Visual Perception Test-3 (MVPT-3) to Koreans and investigate the change in visual-perceptual function using the MVPT-3 in healthy Korean adults. METHODS: The Korean version of the MVPT-3 was developed through a cross-cultural adaptation process according to 6 steps, including translation, reconciliation, back translation, cognitive debriefing, feedback, and final reconciliation. A total of 321 healthy Korean volunteers (mean age, 51.05 years) were recruited. We collected participant demographic data, such as sex, age, and years of education, and performed the Korean version of the Mini-Mental State Examination (K-MMSE) and MVPT-3. Internal consistency of the MVPT-3 and the relationships between demographic data, K-MMSE and MVPT-3 scores were analyzed. The results of this study were compared with published data from western countries including the United States and Canada. RESULTS: Total score on the MVPT-3 was positively correlated with years of education (r=0.715, p<0.001) and K-MMSE score (r=0.718, p<0.001). However, it had a negative correlation with age (r=-0.669, p<0.001). A post-hoc analysis of MVPT-3 scores classified age into 5 groups of < or =49, 50-59, 60-69, 70-79, > or =80 years and years of education into 4 groups of 0, 1-9, 10-12, > or =13 years. No significant differences in MVPT-3 scores were observed according to sex or country. CONCLUSION: Visual perception was significantly influenced by age, years of education, and cognitive function. Reference values for the MVPT-3 provided in this study will be useful for evaluating and planning a rehabilitation program of visual perceptual function in patients with brain disorders.
Adult* ; Brain Diseases ; Canada ; Cognition Disorders ; Education ; Humans ; Reference Values ; Rehabilitation ; United States ; Visual Perception* ; Volunteers

BACKGROUNDAlthough exercise testing has been suggested to help predict clinical outcome, limited data are available to guide how exercise Doppler echocardiography (ECG) can be used clinically in asymptomatic patients with aortic stenosis (AS). The aim of this study was to assess the clinical value of exercise echocardiographic testing in asymptomatic patients with severe AS.

METHODSSymptom-limited treadmill exercise testing using the modified Bruce protocol was performed in 31 asymptomatic patients (mean age (62 ± 11) years) with severe AS (aortic valve area <1 cm(2), peak aortic velocity (AV Vmax) >4 m/sec, or a mean transaortic pressure gradient (AV mean PG) >40 mmHg (1 mmHg = 0.133 kPa)) with normal left ventricular (LV) systolic function (LV ejection fraction (EF) >50%). Clinical symptoms, vital signs, ECG, and Doppler hemodynamics were obtained during and/or immediately after exercise.

RESULTSAortic valve replacement (AVR) was performed in 18 patients during follow-up. The patients who had AVR exhibited higher baseline AV mean PG (51 (35-84) vs. 44 (25.2-57.0) mmHg; P = 0.031). There were no significant differences between the AVR group and non-AVR group including exercise duration (7.47 (2.32-11.59) vs. 7.25 (4.06-10.52) minutes, P = 0.917), exercise capacity (10.1 (4.6-12.8) vs. 10.1 (7.0-12.8) metabolic equivalents, P = 0.675), and an increment in AV mean PG by exercise (18.5 (3.2-48.0) vs. 12.6 (4.4-32.1) mmHg, P = 0.366). Univariate regression analysis revealed that independent determinant of AVR was the baseline AV mean PG (P = 0.031).

CONCLUSIONSAlthough additional value of exercise ECG was demonstrated, baseline transaortic mean pressure gradient is the major determinant of AVR. Further large-scale prospective studies are required to determine whether surgery should be recommended in the presence of an abnormal exercise ECG in asymptomatic severe AS.