Purpose: This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC). Materials and Methods: This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models. Results: Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course. Conclusion Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

Immunonutrition, which uses specific nutrients to modulate the immune response, has emerged as a vital adjunct to perioperative care. Surgery-induced stress triggers immune responses that can lead to complications, such as infections and delayed wound healing. Traditional nutritional support often overlooks the immunological needs of surgical patients. Immunonutrition addresses this oversight by providing key nutrients, such as arginine, omega-3 fatty acids, glutamine, nucleotides, and antioxidants (vitamins C and E) to enhance immune function and support tissue repair. This review examined the efficacy and safety of immunonutrition in surgical settings, guided by the recommendations of the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism. Both organizations recommend immunonutrition for high-risk or malnourished patients undergoing major surgery and support its use in reducing complications and improving recovery. The key nutrients in immunonutrition aim to improve immune cell function, reduce inflammation, and enhance wound healing. Clinical studies and meta-analyses have demonstrated that immunonutrition lowers the infection rate, shortens the length of hospital stay, and accelerates recovery. Challenges hindering the clinical application of immunonutrition include cost, logistics, and a lack of standardized and personalized protocols. Future studies should focus on biomarker-driven approaches, pharmacogenomics, and innovative nutrient formulations. Addressing these issues will help to integrate immunonutrition into clinical practice, ultimately improving surgical outcomes and patient recovery.

Background and Objectives: Spermatogonial stem cells (SSCs) are the most primitive cells in spermatogenesis and are the only adult stem cells capable of passing on the genome of a given species to the next generation. SSCs are the only adult stem cells known to exhibit high Oct4 expression and can be induced to self-reprogram into pluripotent cells depending on culture conditions. Epigenetic modulation is well known to be involved in the induction of pluripotency of somatic cells. However, epigenetic modulation in self-reprogramming of SSCs into pluripotent cells has not been studied. Methods: and Results: In this study, we examined the involvement of epigenetic modulation by assessing whether selfreprogramming of SSCs is enhanced by treatment with epigenetic modulators. We found that second-generation selective class I HDAC inhibitors increased SSC reprogramming efficiency, whereas non-selective HDAC inhibitors had no effect. Conclusions We showed that pluripotent stem cells derived from adult SSCs by treatment with small molecules with epigenetic modulator functions exhibit pluripotency in vitro and in vivo. Our results suggest that the mechanism of SSC reprogramming by epigenetic modulator can be used for important applications in epigenetic reprogramming research.

Objective: To identify the prevalence and characteristics of neuropathic pain (NP) in patients with spinal cord injury (SCI) and to investigate associations between NP and demographic or disease-related variables. Methods: We retrospectively reviewed medical records of patients with SCI whose pain was classified according to the International Spinal Cord Injury Pain classifications at a single hospital. Multiple statistical analyses were employed. Patients aged <19 years, and patients with other neurological disorders and congenital conditions were excluded. Results: Of 366 patients, 253 patients (69.1%) with SCI had NP. Patients who were married or had traumatic injury or depressive mood had a higher prevalence rate. When other variables were controlled, marital status and depressive mood were found to be predictors of NP. There was no association between the prevalence of NP and other demographic or clinical variables. The mean Numeric Rating Scale (NRS) of NP was 4.52, and patients mainly described pain as tingling, squeezing, and painful cold. Females and those with below-level NP reported more intense pain. An NRS cut-off value of 4.5 was determined as the most appropriate value to discriminate between patients taking pain medication and those who did not. Conclusion In total, 69.1% of patients with SCI complained of NP, indicating that NP was a major complication. Treatment planning for patients with SCI and NP should consider that marital status, mood, sex, and pain subtype may affect NP, which should be actively managed in patients with an NRS ≥4.5.

OBJECTIVES: The purpose of this study was to develop a systematic and standardized「The Survey on School Foodservice Program」that can identify the current status of school meals on the nationwide level. METHODS: This study was carried out in six steps of the analysis of report/investigation data related to school foodservice in metropolitan and provincial offices of education, analysis of preceding research related to the actual status of school foodservice, field verification of the actual condition of the school foodservice site, development of a draft of「The Survey on School Foodservice Program」, pilot study of a draft of 「The Survey on School Foodservice Program」, and suggestions of a final model of「The Survey on School Foodservice Program」from August to December, 2017. Statistical analysis was performed for frequency analysis and descriptive analysis using the SPSS program ver. 23. RESULTS: A draft of「The Survey on School Foodservice Program」was developed by analyzing the current status of report/research data on school meals in metropolitan and provincial offices of education, analyzing the preceding research on school meals, and identifying the actual conditions at school foodservice sites. To verify the validity of the school foodservice survey questionnaire, 1,031 schools were sampled from a total of 10,251 schools and the pilot test of ‘2017 School Foodservice Survey’ was conducted. The final model of「The Survey on School Foodservice Program」consisted of 12 survey sections, 29 survey categories, and 433 survey items, and the survey cycle was set for one year and three years for each survey item. CONCLUSIONS: Based on the objective statistical data through「The Survey on School Foodservice Program」, it is possible to develop the school foodservice policy, which will help establish the reliability of the school meals.
Education ; Humans ; Meals ; Pilot Projects

OBJECTIVES: The purpose of this study was to develop a systematic and standardized「The Survey on School Foodservice Program」that can identify the current status of school meals on the nationwide level. METHODS: This study was carried out in six steps of the analysis of report/investigation data related to school foodservice in metropolitan and provincial offices of education, analysis of preceding research related to the actual status of school foodservice, field verification of the actual condition of the school foodservice site, development of a draft of「The Survey on School Foodservice Program」, pilot study of a draft of 「The Survey on School Foodservice Program」, and suggestions of a final model of「The Survey on School Foodservice Program」from August to December, 2017. Statistical analysis was performed for frequency analysis and descriptive analysis using the SPSS program ver. 23. RESULTS: A draft of「The Survey on School Foodservice Program」was developed by analyzing the current status of report/research data on school meals in metropolitan and provincial offices of education, analyzing the preceding research on school meals, and identifying the actual conditions at school foodservice sites. To verify the validity of the school foodservice survey questionnaire, 1,031 schools were sampled from a total of 10,251 schools and the pilot test of ‘2017 School Foodservice Survey’ was conducted. The final model of「The Survey on School Foodservice Program」consisted of 12 survey sections, 29 survey categories, and 433 survey items, and the survey cycle was set for one year and three years for each survey item. CONCLUSIONS: Based on the objective statistical data through「The Survey on School Foodservice Program」, it is possible to develop the school foodservice policy, which will help establish the reliability of the school meals.
Education ; Humans ; Meals ; Pilot Projects

BACKGROUND/AIMS: The aim of this study was to evaluate the effect of the synthetic S-allyl-l-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats. METHODS: The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured. RESULTS: As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats. CONCLUSIONS: These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach.
Aging ; Animals ; Antioxidants ; Blotting, Western ; Child, Preschool ; Connective Tissue ; Diet ; Enzyme-Linked Immunosorbent Assay ; Gastric Acid* ; Heme ; Humans ; Inflammation* ; Interleukins ; Lansoprazole ; Mucous Membrane ; Oxidative Stress ; Rats* ; Stomach* ; Tumor Necrosis Factor-alpha

BACKGROUND: The aim of this study was to evaluate the anti-inflammatory and anti-tumorigenic effect of açai berry after chronic Helicobacter felis colonization in the stomachs of C57BL/6 mice. METHODS: A total of 57 four-week-old female C57BL/6 mice (18 control mice and 39 experimental mice) were used. The mice were administered orogastrically with vehicle only or vehicle containing H. felis, 5 times every other day. After inoculation of H. felis, mice were fed either a standard or an açai-containing diet and then sacrificed at 4, 24, and 52 weeks. The infection status and degree of inflammation were determined by culture and histopathology. The level of gastric mucosal myeloperoxidase (MPO), TNF-α, and interleukin-1β (IL-1β) were measured by ELISA. RESULTS: At 24 weeks after inoculation, mucosal atrophy and mucous metaplasia appeared in all infected mice. At 52 weeks after inoculation, dysplastic change was noted in 10%, 25%, and 50% of mice in the H. felis-control, H. felis-açai 5%, and H. felis-açai 10% groups, respectively. The neutrophil, monocyte, atrophy, and metaplasia grades of infected mice showed no significant difference among the H. felis-infected groups. H. felis-infected mice fed with açai berry showed no significant difference compared with H. felis-infected control mice in gastric mucosal MPO, TNF-α, and IL-1β levels. CONCLUSIONS: H. felis that colonized the stomachs of C57BL/6 mice provoked inflammation, and induced mucosal atrophy, metaplasia, and dysplasia. However, açai berry did not effectively prohibit the gastric carcinogenesis which was induced by chronic H. felis infection.
Animals ; Atrophy ; Carcinogenesis ; Cats ; Colon ; Diet ; Enzyme-Linked Immunosorbent Assay ; Felis ; Female ; Fruit* ; Helicobacter felis ; Helicobacter* ; Humans ; Inflammation ; Metaplasia ; Mice* ; Monocytes ; Neutrophils ; Peroxidase ; Stomach

BACKGROUND/AIMS: This study was aimed at evaluating differences in the effects of repeated water avoidance stress (rWAS) on colonic movement, mucosal mast cell counts, cytokine levels, and visceromotor response (VMR) to colorectal distension (CRD) in rats of both sexes. METHODS: Wistar rats were divided into stress and no-stress groups. Rats in the stress group were exposed to rWAS (1 hr/day) for 10 days. Mucosal mast cells were immunohistochemically stained with anti-mast cell tryptase antibody and counted. The colonic mucosal cytokine levels were measured with enzyme-linked immunosorbent assay. The VMR to CRD (visceral analgesia) was assessed by using a barostat and noninvasive manometry. RESULTS: The mean number of fecal pellets in the rWAS group increased significantly as compared with that in the no-stress group in both sexes. After adjustment for body weight, the female rats had a significantly higher pellet output than the male rats. The mucosal mast cell count of the female rWAS group was higher than that of the male rWAS group (13.0 ± 0.9 vs 8.8 ± 0.6; P < 0.001). The colonic mucosal interleukin-1β level was also higher only in the female rats of the rWAS group than in those of the no-stress group. On days 10 and 11, a decrease in VMR to CRD was observed at 40 and 60 mmHg in both sexes of the rWAS group, without a sex-based difference. CONCLUSIONS: The colonic response to stress appeared to be more sensitive in the female rats than in the male rats. However, stress-induced visceral analgesia had no sex-related difference and the underlying mechanism needs to be further evaluated.
Analgesia ; Animals ; Body Weight ; Colon* ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Manometry ; Mast Cells* ; Rats ; Rats, Wistar* ; Sex Characteristics* ; Tryptases ; Water*