Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

BACKGROUND: Cryopreservation can cause mechanical and chemical stress, ultimately leading to the formation of reactive oxygen species (ROS) and oxidative stress. ROS inhibits the expression of antioxidant enzymes in cells, resulting in increased DNA fragmentation and apoptosis. In this paper, we used a vitrification method that has the advantage of producing less ice crystal formation, cost-effectiveness, and time efficiency during cryopreservation. The objective of this paper is to evaluate the degree of protection of ovarian tissue against oxidative stress when N-acetylcysteine (NAC) and Klotho proteins are treated in the vitrification process of ovarian tissue. METHODS: The control group and the cryopreservation groups were randomly assigned, and treated NAC, Klotho, or the combination (NAC ? Klotho). The cell morphological change, DNA damage, senescence, and apoptosis of each group after the freeze–thaw process were compared using transmission electron microscopy, immunohistochemistry, and western blot analysis. RESULTS: Both NAC and Klotho were found to be more effective at protecting against DNA damage than the control;however, DNA damage was greater in the NAC ? Klotho group than in the group treated with NAC and Klotho, respectively. DNA damage and cellular senescence were also reduced during the vitrification process when cells were treated with NAC, Klotho, or the combination (NAC ? Klotho). NAC increased apoptosis during cryopreservation, whereas Klotho inhibited apoptosis and NAC-induced apoptosis. CONCLUSION This study highlights Klotho’s benefits in inhibiting DNA damage, cell senescence, and apoptosis, including NAC-induced apoptosis, despite its unclear role in vitrification.

Purpose: To evaluate the efficacy and safety of udenafil 75 mg once daily in patients with erectile dysfunction following bilateral nerve-sparing robot-assisted laparoscopic radical prostatectomy (BNS-RALP). Materials and Methods: A multi-center, prospective, randomized, controlled, double-blind study was conducted. Among patients with localized prostate cancer with international index of erectile function-erectile function domain (IIEF-EF) score of 18 or higher before BNS-RALP, those who developed postoperative erectile dysfunction (IIEF-EF score 14 or less at 4 weeks after BNS-RALP) were enrolled. Enrolled patients were randomly assigned to the udenafil 75 mg daily group or the placebo group in a 2:1 ratio. Each subject was followed up at 8 weeks (V2), 20 weeks (V3), and 32 weeks (V4) to evaluate the efficacy and safety of udenafil. Results: In all, 101 patients were screened, of whom 99 were enrolled. Of the 99 patients, 67 were assigned to the experimental group and 32 to the control group. Ten (14.93%) patients in the experimental group and 10 (31.25%) in the control group dropped out of the study. After 32 weeks of treatment, IIEF-EF score of 22 or higher was seen in 36.51% (23/63) of patients in the experimental group and 13.04% (3/23) patients in the control group (p=0.021). The proportion of patients with IIEF-EF improvement of 25% or more compared to the baseline was 82.54% (52/63) in the experimental group and 62.96% (17/27) in the control group (p=0.058). Conclusions Udenafil 75 mg once daily after BNS-RALP improved the erectile function without any severe adverse effects.

Background/Aims: The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.
Methods: Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.
Results: HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.
Conclusions The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.

PURPOSE: To investigate the relationship of improvement in erectile function (EF) with improvement in lower urinary tract symptoms (LUTS) and to assess the contribution of tamsulosin dose to the improvement of EF apart from the indirect influence of LUTS improvement in men with LUTS and erectile dysfunction (ED). MATERIALS AND METHODS: Fifty patients received tamsulosin 0.2 mg/d for the first 4 weeks and were subsequently divided into two groups by patient-reported outcomes. Nonescalators were maintained starting dose and escalators increased to 0.4 mg for the remaining 8 weeks. International Prostatic Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5), and underwent uroflowmetry were evaluated at baseline, and weeks 4 and 12. RESULTS: LUTS parameters were significantly improved in both groups but insignificant between the 2 groups. The degree of the improvement in the total IPSS and in the voiding, storage, and quality of life (QoL) subscores were significantly correlated with the degree of the improvement in EF; this was especially prominent in patients successfully treated LUTS. The escalators experienced a significantly greater increase in IIEF-5 scores than did the nonescalators (3.3 vs. 1.5). CONCLUSIONS: Dose escalation provided similar LUTS improvement in patients with refractory to starting dose. The improvements of LUTS were correlated with the improvement of EF. The increase in the IIEF-5 score was significantly higher in escalators. These findings imply that tamsulosin may contribute to the improvement in EF through the improvement of LUTS and QoL and direct relaxation of the corpus cavernosum in a dose-dependent fashion.
Elevators and Escalators ; Erectile Dysfunction ; Humans ; Lower Urinary Tract Symptoms ; Male ; Prostatic Hyperplasia ; Quality of Life ; Relaxation ; Sulfonamides

Evidence suggests that diabetes mellitus (DM) is associated with idiopathic pulmonary fibrosis (IPF). According to the new IPF guidelines, high-resolution computed tomography (HRCT) is an essential means of diagnosing IPF. We investigated the relationship between IPF and DM in patients treated between 2003 and 2007. Newly diagnosed IPF patients in large university teaching hospitals in Korea were enrolled from January 2003 to December 2007. We retrospectively analyzed 1,685 patients using the interstitial lung disease (ILD) registry. In total, 299 IPF patients (17.8%) also had DM. The mean age of our subjects was 68.0 +/- 9.4 yr. HRCT showed significantly more reticular and honeycomb patterns in IPF patients with DM than in IPF patients without DM (P = 0.014, P = 0.028, respectively). Furthermore, significantly higher incidences of hypertension, cardiovascular diseases, and other malignancies (except lung cancer) were found in IPF patients with DM than in IPF patients without DM. In conclusion, IPF patients with DM are more likely to have the usual interstitial pneumonia (UIP) pattern, including reticular and honeycomb patterns, on HRCT than are those without DM.
Aged ; Cardiovascular Diseases/epidemiology/etiology ; Diabetes Mellitus, Type 2/*complications ; Female ; Humans ; Hypertension/epidemiology/etiology ; Idiopathic Pulmonary Fibrosis/complications/*diagnosis/radiography ; Incidence ; Male ; Middle Aged ; Neoplasms/epidemiology/etiology ; Registries ; Republic of Korea/epidemiology ; Retrospective Studies ; Tomography, X-Ray Computed

Recently, there have been many changes in the area of healthcare. There is no certainty how these changes will affect the healthcare system and public health. However, to at least have these changes positively implemented, it is clear that evaluation through continuous monitoring is necessary. The enforcement of the Medical Institution Accreditation and Medical Dispute Mediation Law as well as legal revisions regarding the public healthcare system are changes to improve the quality of healthcare, while at the same time, provide penalties for infractions of the new law such as medicine/medical device rebates; moreover, legal revisions regarding telemedicine are anticipated to impartially vitalize technical development as well as the pharmaceutical industry. For these changes to have a positive effect on the medical field and people's lives, an accurate comprehension of the system and understanding of the details is necessary to be able to respond sensitively to any changes in the future. Therefore, this paper examined the background information on the current discussion on the changes in the healthcare system, examined the detailed content of the system, and reviewed the areas that were in dispute as well as the main issues to contemplate the expected effects of the changes and future tasks that may be generated as a result. These considerations will act as foundation for an in depth understanding of recent trends in the healthcare system.
Accreditation/legislation & jurisprudence ; Delivery of Health Care/*legislation & jurisprudence ; Health Care Reform ; Humans ; Quality of Health Care ; Telemedicine

Multiple primary cancers are the occurrence of more than two cancers of different origin in an individual. Penile cancer is a rare disease, and finding it combined with other cancers is even rarer. A 64-year-old man with a painful penile mass was referred to us from a primary urological clinic. We performed a biopsy of the penile mass and the histology revealed a well-differentiated squamous cell carcinoma. Abdominal computed tomography showed a localized bladder tumor with inguinal lymphadenopathy. The patient underwent a partial penectomy, transurethral resection of the bladder tumor and inguinal lymph node dissection. The histology of the bladder tumor was high-grade papillary carcinoma, and that of the lymph node was squamous cell carcinoma. The penile and bladder tumors were in stage II (T1N1M0) and stage I (T1N0M0), respectively. We successfully treated the patient with adjuvant radiotherapy and systemic chemotherapy.
Biopsy ; Carcinoma, Papillary ; Carcinoma, Squamous Cell ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Diseases ; Male ; Middle Aged ; Penile Neoplasms ; Radiotherapy, Adjuvant ; Rare Diseases ; Urinary Bladder ; Urinary Bladder Neoplasms