Purpose: This study aimed to evaluate clinical significance and imaging findings of newly detected lesions on breast MRI while monitoring patients’ response to neoadjuvant chemotherapy (NAC). Materials and Methods: We identified 291 patients with newly diagnosed breast cancer who underwent breast MRI to assess their response to NAC between January 2017 and August 2021. We evaluated 26 new lesions in 24 women (mean age, 49.8 years; range, 35–63 years) who were included in this study. Two radiologists assessed imaging findings of new lesions according to Breast Imaging Reporting and Data System (BI-RADS) lexicon 5th edition and evaluated follow-up MRI during NAC. Outcomes of new lesions were determined based on pathologic examination or imaging follow-up after surgery. Results: All 26 new lesions were found on the first follow-up imaging. They disappeared or decreased in size on the second follow-up imaging. Lesion types included mass (n = 22, 84.6%) and non-mass enhancement (n = 4, 15.4%). The majority of the mass types showed oval to round shapes (22/22, 100%), circumscribed margins (21/22, 95.5%), and rim enhancement (18/22, 81.8%). Seven (26.9%) new lesions were ipsilateral to the index cancer, 7 (26.9%) were contralateral, and 12 (46.2%) were bilateral. None of these new lesions were malignant. Conclusion New lesions were detected in 4.7% of breast MRI during NAC. Most new lesions tended to

PURPOSE: Testosterone replacement therapy is an effective treatment for late-onset hypogonadism (LOH) despite a few contraindications and side-effects. The aim of this study was to determine whether modified Ojayeonjonghwan (KH-204, Korean herbal formula) improved LOH. KH-204 is a strong antioxidant herbal formula. We evaluated the effect of Korean herbal prescription on androgen receptor (AR) expression in an aged rat model of LOH. MATERIALS AND METHODS: Eighteen-month-old rats were used as aged LOH rat models. Eighteen Sprague-Dawley rats were randomly divided into three equal groups of six animals each and treated with one of the following: 1) normal control group (oral administration with distilled water, n=6), 2) KH-204 200 group (oral administration with 200 mg/kg of KH-204, n=6), and 3) KH-204 400 group (oral administration with 400 mg/kg of KH-204, n=6). After four weeks of treatment (once daily, distilled water or KH-204), serum testosterone levels, changes in testicular and epididymal weight, Western blotting analysis of AR expression and measurement of oxidative stress were examined. RESULTS: Treatment with the herbal formulation KH-204 200 mg/kg and 400 mg/kg (1) increased the weights of testis and epididymis; (2) increased the level of serum testosterone; (3) increased the level of superoxide dismutase and reduced the level of 8-hydroxy-20-deoxyguanosine; and (4) upregulated AR expression in testicular tissue. CONCLUSIONS: KH-204 might be an effective alternative for LOH. It improves antioxidant mechanisms and increases testicular AR expression without side-effects.
Aging* ; Animals ; Blotting, Western ; Epididymis ; Hypogonadism* ; Male ; Models, Animal* ; Oxidative Stress ; Phytotherapy ; Prescriptions ; Rats* ; Rats, Sprague-Dawley ; Receptors, Androgen* ; Superoxide Dismutase ; Testis ; Testosterone ; Water ; Weights and Measures

Vacuolar protein sorting-associated protein 13B (VPS13B), also known as COH1, is one of the VPS13 family members which is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Mutations in the VPS13B gene are associated with Cohen syndrome and other cognitive disorders such as intellectual disabilities and autism spectrum disorder (ASD). However, the patho-physiology of VPS13B-associated cognitive deficits is unclear, in part, due to the lack of animal models. Here, we generated a Vps13b exon 2 deletion mutant mouse and analyzed the behavioral phenotypes. We found that Vps13b mutant mice showed reduced activity in open field test and significantly shorter latency to fall in the rotarod test, suggesting that the mutants have motor deficits. In addition, we found that Vps13b mutant mice showed deficits in spatial learning in the hidden platform version of the Morris water maze. The Vps13b mutant mice were normal in other behaviors such as anxiety-like behaviors, working memory and social behaviors. Our results suggest that Vps13b mutant mice may recapitulate key clinical symptoms in Cohen syndrome such as intellectual disability and hypotonia. Vps13b mutant mice may serve as a useful model to investigate the pathophysiology of VPS13B-associated disorders.
Animals ; Autism Spectrum Disorder ; Cognition Disorders ; Exons ; Humans ; Intellectual Disability ; Learning Disorders ; Memory, Short-Term ; Mice ; Models, Animal ; Muscle Hypotonia ; Phenotype ; Rotarod Performance Test ; Social Behavior ; Spatial Learning ; Water

Red Liriope platyphylla (RLP) is a known herbal medicine used in the treatment of some chronic diseases including constipation, neurodegenerative disorders, diabetes and obesity. To determine and characterize putative biomarkers that predict the laxative effects induced by RLP treatment, alteration of endogenous metabolites was measured in the serum of loperamide (Lop)-induced constipation rats after administration of RLP extract (EtRLP) using 1H nuclear magnetic resonance (1H NMR) spectral data. The urine volume and amounts, and weights and water contents of stools were significantly recovered in the Lop + EtRLP treated group as compared to the No group, whereas body weight and food intake maintained constant levels. Also, significant recoveries in the thickness of mucosa and muscle were detected in the colon of the Lop + EtRLP treated group. Furthermore, pattern recognition showed absolutely different clustering of the serum analysis parameters when comparing the Lop treated group and Lop + EtRLP treated group. Of the 33 endogenous metabolites, 7 amino acids (alanine, arginine, glutamate, glutamine, glycine, threonine and valine) and 8 endogenous metabolites (betaine, creatine, glucose, taurine, ethanol, lactate, glycerol and succinate) were dramatically increased in the Lop + EtRLP treated SD rats. These results provide the first evidence pertaining to metabolic changes in the constipation rats treated with Lop + EtRLP. Additionally, these findings correlate with changes observed in 15 metabolites during the laxative effects of EtRLP.

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

BACKGROUND: The Korea Radiation Effect & Epidemiology Cohort METHODS: Using the KREEC-R raw data, we calculated age standardized rates (ASRs) of female thyroid cancer and re-analyzed the results of survey on the use of medical services. We also marked the administrative districts of residents who received the Radiation Health Research Institute (RHRI) health examinations and those in which thyroid cancer case occurred as per the Chonnam National University Research Institute of Medical Sciences (RIMS) final report on maps where the locations of NPPs and 5 km-radii around them were also indicated. And we compared the incidence rates of Radiation-induced cancer measured between the first period when RHRI health examinations were not yet implemented, and the second period when the RHRI health examinations were implemented. RESULTS: The ASR for the far-distance group, which comprised residents living in areas outside the 30 km radius of the NPPs, increased rapidly after 2000; however, that of the exposed group, which comprised residents living within a 5 km radius of the NPPs, started to increase rapidly even before 1995. The frequencies of the use of medical services were significantly higher in the intermediate proximate group, which comprised residents living within a 5–30 km radius of the NPPs, than in the exposed group in women. In case of female thyroid cancer, the second period ASR was higher than the first period ASR, but in case of female liver cancer and female stomach cancer no significant difference were observed between the periods. On map, many administrative districts of residents who received RHRI health examinations and most administrative districts in which thyroid cancer case occurred on RIMS final report were outside 5 km-radii around NPPs. CONCLUSIONS: We could not find any evidence supporting the assertion that detection bias influenced the increased risks of female thyroid cancer observed in the exposed group of the KREEC-R study, as opposed to the control group.
Academies and Institutes ; Bias (Epidemiology) ; Cohort Studies ; Epidemiology ; Female ; Humans ; Incidence ; Jeollanam-do ; Korea ; Liver Neoplasms ; Neoplasms, Radiation-Induced ; Nuclear Power Plants ; Radiation Effects ; Radius ; Stomach Neoplasms ; Thyroid Gland ; Thyroid Neoplasms

BACKGROUND/AIMS: Endoscopic resection (ER) is a well-established treatment modality for gastric epithelial neoplasm. However, there is a discrepancy between forceps biopsy and ER specimen pathology, including a negative pathologic diagnosis (NPD) after ER. It has been suggested that pit dysplasia (PD) is a subtype of gastric dysplasia, and the aim of this study was to assess the significance of PD in cases with NPD after ER for early gastric neoplasms. METHODS: After ER, 29 NPD lesions that had an associated pretreatment forceps biopsy specimen, were correctly targeted during ER, and had no cautery artifact on the resected specimen were included in this study. RESULTS: Sixteen lesions showed PD and 13 had no neoplastic pathology. The initial pretreatment forceps biopsy diagnoses of 29 NPD lesions were low-grade dysplasia (LGD) in 17 lesions, high-grade dysplasia (HGD) in seven lesions, and adenocarcinoma in five lesions, which after review were revised to PD in 19 lesions, LGD in four lesions, adenocarcinoma in two lesions, and no neoplastic pathology in four lesions. Overall, nine lesions (31%) were small enough to be removed by forceps biopsy, four NPD lesions (14%) were initially misinterpreted as neoplastic lesions, and 16 PD lesions (55%) were misinterpreted as NPD lesions on ER slides. CONCLUSIONS: Approximately half of the lesions initially diagnosed as LGD or HGD were subsequently classified as PD. Therefore, including PD as a subtype of gastric dysplasia could reduce the diagnostic discrepancy between initial forceps biopsy and ER specimens.
Adenocarcinoma ; Artifacts ; Biopsy ; Cautery ; Diagnosis ; Neoplasms, Glandular and Epithelial* ; Pathology* ; Stomach ; Stomach Neoplasms ; Surgical Instruments

PURPOSE: To investigate the production of long pentraxin 3 (PTX3) in response to tunicamycin-induced endoplasmic reticulum (ER) stress and its role in ER stress-associated cell death, PTX3 expression was evaluated in the human retinal pigment epithelial cell line, ARPE-19. METHODS: PTX3 production in ARPE-19 cells was analyzed in the absence or presence of tunicamycin treatment by enzyme-linked immunosorbent assay. PTX3 protein and mRNA levels were estimated using western blot analysis and real-time reverse transcription-polymerase chain reaction, respectively. Protein and mRNA levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and ARPE-19 cell viability were measured in the presence of tunicamycin-induced ER stress in control or PTX3 small hairpin RNA (shRNA)-transfected ARPE-19 cells. RESULTS: The protein and mRNA levels of PTX3 were found to be significantly increased by tunicamycin treatment. PTX3 production was significantly decreased in inositol-requiring enzyme 1α shRNA-transfected ARPE-19 cells compared to control shRNA-transfected cells. Furthermore, pretreatment with the NF-κB inhibitor abolished tunicamycin-induced PTX3 production. Decreased cell viability and prolonged protein and mRNA expression of CHOP were observed under tunicamycin-induced ER stress in PTX3 shRNA transfected ARPE-19 cells. CONCLUSIONS: These results suggest that PTX3 production increased in the presence of tunicamycin-induced ER stress. Therefore, PTX3 could be an important protector of ER stress-induced cell death in human retinal pigment epithelial cells. Inositol-requiring enzyme 1α and the NF-κB signaling pathway may serve as potential targets for regulation of PTX3 expression in the retina. Therefore, their role in PTX3 expression needs to be further investigated.
Anti-Bacterial Agents/pharmacology ; Apoptosis ; Blotting, Western ; C-Reactive Protein/biosynthesis/*genetics ; Cells, Cultured ; Endoplasmic Reticulum Stress/*drug effects/genetics ; Enzyme-Linked Immunosorbent Assay ; *Gene Expression Regulation ; Humans ; Polymerase Chain Reaction ; RNA, Messenger/*genetics ; Retinal Pigment Epithelium/*metabolism/pathology ; Serum Amyloid P-Component/biosynthesis/*genetics ; Tunicamycin/*pharmacology

PURPOSE: We compared a transperineal ligation model and a transperitoneal ligation model in male rats to determine which animal model of overactive bladder (OAB) was more useful based on cystometrography, estimations of oxidative stress, and measurements of pro-inflammatory cytokine levels. MATERIALS AND METHODS: Male rats were randomly divided into three groups (n=15 in each): the control group, the transperineal ligation group, and the transperitoneal ligation group. Four weeks after the ligation procedure, cystometrography was performed and oxidative stress, pro-inflammatory cytokine levels, and histologic changes were evaluated. Oxidative stress was assessed by measuring 8-hydroxy-20-deoxyguanosine and superoxide dismutase, and pro-inflammatory cytokine activity was investigated by measuring levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α. RESULTS: The transperineal model led to results similar to those observed for the transperitoneal model, namely (1) increased voiding frequency and reductions in the non-voiding contraction interval and the maximal vesical pressure, (2) increased levels of oxidative stress markers, (3) increased pro-inflammatory cytokine levels, and (4) fibrotic changes in the bladder tissue. CONCLUSIONS: We suggest that the transperineal procedure can be used as an alternative OAB model in male rats.
Animals* ; Humans ; Interleukin-8 ; Interleukins ; Ligation* ; Male* ; Models, Animal* ; Necrosis ; Oxidative Stress ; Rats* ; Superoxide Dismutase ; Urinary Bladder ; Urinary Bladder Neck Obstruction ; Urinary Bladder, Overactive*

PURPOSE: We investigated the protective effects of the herbal formulation KH-204 in the bladder of androgen-deprived rats. MATERIALS AND METHODS: Male rats aged eight weeks were randomly divided into four groups, containing eight rats each: sham operation only (normal control group), androgen-deprived only (androgen-deprived control group), and androgen-deprived followed by treatment with 200 mg/kg or 400 mg/kg of KH-204. After 0.5 mg/kg of leuprorelin was subcutaneously injected in the androgen-deprived groups, the oral administration of either distilled water in the two control groups or KH-204 in the treatment group was continued for four weeks. Serum testosterone levels, RhoGEF levels, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, oxidative stress, and histologic changes were evaluated after treatment. RESULTS: Treatment with the herbal formulation KH-204 (1) increased serum testosterone levels; (2) restored the expression of RhoGEFs, endothelial NO synthase, and neuronal NO synthase; (3) increased the expression of superoxide dismutase; and (4) decreased bladder fibrosis. CONCLUSIONS: Our results suggest that the positive effects of KH-204 on the urinary bladder may be attributed to its antioxidant effects or to an elevation in NO-cGMP activity.
Administration, Oral ; Animals ; Antioxidants ; Fibrosis ; Guanosine Monophosphate ; Humans ; Hypogonadism ; Leuprolide ; Male ; Neurons ; Nitric Oxide ; Nitric Oxide Synthase ; Oxidative Stress ; Phytotherapy ; Rats* ; Rho Guanine Nucleotide Exchange Factors ; Superoxide Dismutase ; Testosterone ; Urinary Bladder* ; Water