Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

It is unclear whether poor glycemic control contributes to residual kidney function (RKF) decline and consequent volume overload in diabetic patients on peritoneal dialysis (PD). Methods: This retrospective analysis included 80 diabetic patients who started PD at a single center. The first 2 years of patient data were collected to investigate the impact of glycemic control on RKF and volume overload in the early stages of PD. We used the time-averaged glycated hemoglobin (HbA1c) levels to estimate glycemic control. RKF loss was measured as the slope of RKF decline and time to anuria. To assess the association between glycemic control and volume overload, we examined technique failure (TF) associated with volume overload (TFVO), defined as TF due to excessive fluid accumulation. Multivariable linear regression and Cox regression analysis were performed to assess how glycemic control affects RKF and TFVO. Results: Over the first 2 years, the mean rate of RKF decline was –3.25 ± 3.94 mL/min/ 1.73 m2 per year. Multivariable linear regression showed that higher time-averaged HbA1c was associated with a rapid RKF decline (β = –0.95; 95% confidence interval [CI], –1.66 to –0.24; p = 0.01). In the adjusted Cox regression analysis, higher time-averaged HbA1c increased the risk of progression to anuria (adjusted hazard ratio [HR], 1.97; 95% CI, 1.29–3.00; p = 0.002) and TFVO (adjusted HR, 2.88; 95% CI, 1.41–5.89; p = 0.004). Conclusion: Poor glycemic control is associated with rapid RKF decline and leads to volume overload in diabetic patients on PD.

Background/Aims: Colonic stenting plays a vital role in the management of acute malignant colonic obstruction. The increasing use of self-expandable metal stents (SEMS) and the diverse challenges posed by colonic obstruction at various locations underscore the importance of effective training for colonic stent placement. Methods: All the components of the simulator were manufactured using silicone molding techniques in conjunction with three-dimensional (3D) printing. 3D images sourced from computed tomography scans and colonoscopy images were converted into a stereolithography format. Acrylonitrile butadiene styrene copolymers have been used in fused deposition modeling to produce moldings. Results: The simulator replicated the large intestine from the rectum to the cecum, mimicking the texture and shape of the human colon. It enables training for colonoscopy insertion, cecum intubation, loop reduction, and stenting within stenotic areas. Interchangeable stenotic modules for four sites (rectum, sigmoid colon, descending colon, and ascending colon) were easily assembled for training. These modules integrate tumor contours and blood vessel structures with a translucent center, allowing real-time visualization during stenting. Successful and repeatable demonstrations of stent insertion and expansion using the reusable SEMS were consistently achieved. Conclusions This innovative simulator offers a secure colonic stenting practice across various locations, potentially enhancing clinical outcomes by improving operator proficiency during actual procedures.

Pedicle ossification is a rare but significant complication following mandibular reconstruction using a fibular free flap (FFF), a technique widely employed in maxillofacial surgery due to its reliable vascularized bone supply and low donor site morbidity. The FFF supports dental implantation and prosthetic rehabilitation, with its vascularized periosteum enhancing osteogenic potential. Despite these advantages, unexpected ossification of the flap’s vascular pedicle may occur, potentially mimicking tumor recurrence and causing diagnostic uncertainty. This case report describes a 38-year-old male with left buccal squamous cell carcinoma treated by wide excision, modified radical neck dissection, and reconstruction using a radial forearm free flap. Postoperative radiotherapy led to complications including trismus and alveolar bone exposure, culminating in a pathological mandibular fracture. Mandibular reconstruction was performed using an FFF. Over 4 years of follow-up, computed tomography revealed ossification within the vascular pedicle. Notably, the patient remained asymptomatic, maintaining normal speech and swallowing without functional impairment. Pedicle ossification may present radiographically as a suspicious bony change misinterpreted as tumor recurrence. Routine follow-up imaging such as computed tomography is essential for differentiation. Although trismus, bony swelling, or pain may occur, surgical intervention is typically deferred unless symptoms develop. Therefore, careful clinical assessment and monitoring remain crucial.

Purpose: This study aims to analyze the learning curve of hand-assisted laparoscopic living donor nephrectomy (HLDN) conducted by a trained gastrointestinal surgeon. Methods: A retrospective analysis was performed on the perioperative clinical data of 96 consecutive patients who underwent HLDN from May 2013 to March 2023. The learning curve was evaluated using the cumulative sum (CUSUM) test based on operation time and risk-adjusted CUSUM for postoperative complications. Patients were divided into three groups (novice, development, and competency phases) based on changes in operation time. Patient demographics and perioperative outcomes were compared between each group. Results: Among the patients, 35 were male, with a mean age of 48.9 ± 11.3 years and a mean body mass index (BMI) of 24.5 ± 3.2 kg/m 2 . The novice phase (phase 1) included the first 30 cases, with the development phase (phase 2) up to the 65th case. Operation times were significantly different across phases, averaging 263.2 ± 33.4, 211.1 ± 34.4, and 161.1 ± 31.3 minutes for phases 1, 2, and 3, respectively (P < 0.001). Blood loss decreased gradually across phases (phase 1, 264.7 ± 144.4 mL; phase 2, 239.7 ± 166.3 mL; phase 3, 198.8 ± 103.5 mL), though not statistically significant. BMI impacted operation time only in phase 1. Overall postoperative complications occurred in 13 cases (Clavien-Dindo grade I, 4 cases;grade II, 9 cases), with no significant differences across phases. Conclusion HLDN can be safely performed by a trained gastrointestinal surgeon, with approximately 30 cases needed to achieve proficiency.

Purpose: The original eCura system was designed to stratify the risk of lymph node metastasis (LNM) after endoscopic resection (ER) in patients with early gastric cancer (EGC).We assessed the effectiveness of a modified eCura system for reflecting the characteristics of undifferentiated-type (UD)-EGC. Materials and Methods: Six hundred thirty-four patients who underwent non-curative ER for UD-EGC and received either additional surgery (radical surgery group; n=270) or no further treatment (no additional treatment group; n=364) from 18 institutions between 2005 and 2015 were retrospectively included in this study. The eCuraU system assigned 1 point each for tumors >20 mm in size, ulceration, positive vertical margin, and submucosal invasion <500 µm; 2 points for submucosal invasion ≥500 µm; and 3 points for lymphovascular invasion. Results: LNM rates in the radical surgery group were 1.1%, 5.4%, and 13.3% for the low-(0–1 point), intermediate- (2–3 points), and high-risk (4–8 points), respectively (P-fortrend<0.001). The eCuraU system showed a significantly higher probability of identifying patients with LNM as high-risk than the eCura system (66.7% vs. 22.2%; McNemar P<0.001).In the no additional treatment group, overall survival (93.4%, 87.2%, and 67.6% at 5 years) and cancer-specific survival (99.6%, 98.9%, and 92.9% at 5 years) differed significantly among the low-, intermediate-, and high-risk categories, respectively (both P<0.001). In the high-risk category, surgery outperformed no treatment in terms of overall mortality (hazard ratio, 3.26; P=0.015). Conclusions The eCuraU system stratified the risk of LNM in patients with UD-EGC after ER. It is strongly recommended that high-risk patients undergo additional surgery.

Pedicle ossification is a rare but significant complication following mandibular reconstruction using a fibular free flap (FFF), a technique widely employed in maxillofacial surgery due to its reliable vascularized bone supply and low donor site morbidity. The FFF supports dental implantation and prosthetic rehabilitation, with its vascularized periosteum enhancing osteogenic potential. Despite these advantages, unexpected ossification of the flap’s vascular pedicle may occur, potentially mimicking tumor recurrence and causing diagnostic uncertainty. This case report describes a 38-year-old male with left buccal squamous cell carcinoma treated by wide excision, modified radical neck dissection, and reconstruction using a radial forearm free flap. Postoperative radiotherapy led to complications including trismus and alveolar bone exposure, culminating in a pathological mandibular fracture. Mandibular reconstruction was performed using an FFF. Over 4 years of follow-up, computed tomography revealed ossification within the vascular pedicle. Notably, the patient remained asymptomatic, maintaining normal speech and swallowing without functional impairment. Pedicle ossification may present radiographically as a suspicious bony change misinterpreted as tumor recurrence. Routine follow-up imaging such as computed tomography is essential for differentiation. Although trismus, bony swelling, or pain may occur, surgical intervention is typically deferred unless symptoms develop. Therefore, careful clinical assessment and monitoring remain crucial.

Background/Aims: Colonic stenting plays a vital role in the management of acute malignant colonic obstruction. The increasing use of self-expandable metal stents (SEMS) and the diverse challenges posed by colonic obstruction at various locations underscore the importance of effective training for colonic stent placement. Methods: All the components of the simulator were manufactured using silicone molding techniques in conjunction with three-dimensional (3D) printing. 3D images sourced from computed tomography scans and colonoscopy images were converted into a stereolithography format. Acrylonitrile butadiene styrene copolymers have been used in fused deposition modeling to produce moldings. Results: The simulator replicated the large intestine from the rectum to the cecum, mimicking the texture and shape of the human colon. It enables training for colonoscopy insertion, cecum intubation, loop reduction, and stenting within stenotic areas. Interchangeable stenotic modules for four sites (rectum, sigmoid colon, descending colon, and ascending colon) were easily assembled for training. These modules integrate tumor contours and blood vessel structures with a translucent center, allowing real-time visualization during stenting. Successful and repeatable demonstrations of stent insertion and expansion using the reusable SEMS were consistently achieved. Conclusions This innovative simulator offers a secure colonic stenting practice across various locations, potentially enhancing clinical outcomes by improving operator proficiency during actual procedures.