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.

Objectives: Gastric dysplasia is primarily treated using endoscopic resection. Although argon plasma coagulation (APC) is an alternative treatment for older patients or those with bleeding tendencies, studies have reported a higher rate of local recurrence after APC than after endoscopic resection. Using pathological examinations, this study aimed to investigate the incidence and associated causative factors of residual dysplasia following APC. Methods: This prospective study recruited patients with low-grade gastric dysplasia from March 2020 to February 2021 and conducted follow-up examinations for 15 months after enrollment of the last patient. The patients were randomly assigned to undergo APC at an output power setting of 45, 60, or 80 W. Results: Residual lesions were found in 13 of 68 patients (19.1%) during the 24-h follow-up endoscopy and biopsy. The Ki-67 index, a marker of cellular proliferation, was significantly associated with the presence of residual lesions. The presence of residual dysplasia at the three-month follow-up was associated with the presence of residual lesions at the 24-h follow-up and a positive Ki-67 index. Only three of the 13 patients with residual lesions 24 h after APC demonstrated residual lesions at the three-month follow up. No post-procedural complications were observed. Conclusions Residual dysplasia may persist even after APC and cause local recurrence. If Ki-67-positive cells are detected in the remnant tissue following APC, additional interventions should be considered.

Objectives: Gastric dysplasia is primarily treated using endoscopic resection. Although argon plasma coagulation (APC) is an alternative treatment for older patients or those with bleeding tendencies, studies have reported a higher rate of local recurrence after APC than after endoscopic resection. Using pathological examinations, this study aimed to investigate the incidence and associated causative factors of residual dysplasia following APC. Methods: This prospective study recruited patients with low-grade gastric dysplasia from March 2020 to February 2021 and conducted follow-up examinations for 15 months after enrollment of the last patient. The patients were randomly assigned to undergo APC at an output power setting of 45, 60, or 80 W. Results: Residual lesions were found in 13 of 68 patients (19.1%) during the 24-h follow-up endoscopy and biopsy. The Ki-67 index, a marker of cellular proliferation, was significantly associated with the presence of residual lesions. The presence of residual dysplasia at the three-month follow-up was associated with the presence of residual lesions at the 24-h follow-up and a positive Ki-67 index. Only three of the 13 patients with residual lesions 24 h after APC demonstrated residual lesions at the three-month follow up. No post-procedural complications were observed. Conclusions Residual dysplasia may persist even after APC and cause local recurrence. If Ki-67-positive cells are detected in the remnant tissue following APC, additional interventions should be considered.

Objectives: Gastric dysplasia is primarily treated using endoscopic resection. Although argon plasma coagulation (APC) is an alternative treatment for older patients or those with bleeding tendencies, studies have reported a higher rate of local recurrence after APC than after endoscopic resection. Using pathological examinations, this study aimed to investigate the incidence and associated causative factors of residual dysplasia following APC. Methods: This prospective study recruited patients with low-grade gastric dysplasia from March 2020 to February 2021 and conducted follow-up examinations for 15 months after enrollment of the last patient. The patients were randomly assigned to undergo APC at an output power setting of 45, 60, or 80 W. Results: Residual lesions were found in 13 of 68 patients (19.1%) during the 24-h follow-up endoscopy and biopsy. The Ki-67 index, a marker of cellular proliferation, was significantly associated with the presence of residual lesions. The presence of residual dysplasia at the three-month follow-up was associated with the presence of residual lesions at the 24-h follow-up and a positive Ki-67 index. Only three of the 13 patients with residual lesions 24 h after APC demonstrated residual lesions at the three-month follow up. No post-procedural complications were observed. Conclusions Residual dysplasia may persist even after APC and cause local recurrence. If Ki-67-positive cells are detected in the remnant tissue following APC, additional interventions should be considered.

Objectives: Gastric dysplasia is primarily treated using endoscopic resection. Although argon plasma coagulation (APC) is an alternative treatment for older patients or those with bleeding tendencies, studies have reported a higher rate of local recurrence after APC than after endoscopic resection. Using pathological examinations, this study aimed to investigate the incidence and associated causative factors of residual dysplasia following APC. Methods: This prospective study recruited patients with low-grade gastric dysplasia from March 2020 to February 2021 and conducted follow-up examinations for 15 months after enrollment of the last patient. The patients were randomly assigned to undergo APC at an output power setting of 45, 60, or 80 W. Results: Residual lesions were found in 13 of 68 patients (19.1%) during the 24-h follow-up endoscopy and biopsy. The Ki-67 index, a marker of cellular proliferation, was significantly associated with the presence of residual lesions. The presence of residual dysplasia at the three-month follow-up was associated with the presence of residual lesions at the 24-h follow-up and a positive Ki-67 index. Only three of the 13 patients with residual lesions 24 h after APC demonstrated residual lesions at the three-month follow up. No post-procedural complications were observed. Conclusions Residual dysplasia may persist even after APC and cause local recurrence. If Ki-67-positive cells are detected in the remnant tissue following APC, additional interventions should be considered.

Objectives: Gastric dysplasia is primarily treated using endoscopic resection. Although argon plasma coagulation (APC) is an alternative treatment for older patients or those with bleeding tendencies, studies have reported a higher rate of local recurrence after APC than after endoscopic resection. Using pathological examinations, this study aimed to investigate the incidence and associated causative factors of residual dysplasia following APC. Methods: This prospective study recruited patients with low-grade gastric dysplasia from March 2020 to February 2021 and conducted follow-up examinations for 15 months after enrollment of the last patient. The patients were randomly assigned to undergo APC at an output power setting of 45, 60, or 80 W. Results: Residual lesions were found in 13 of 68 patients (19.1%) during the 24-h follow-up endoscopy and biopsy. The Ki-67 index, a marker of cellular proliferation, was significantly associated with the presence of residual lesions. The presence of residual dysplasia at the three-month follow-up was associated with the presence of residual lesions at the 24-h follow-up and a positive Ki-67 index. Only three of the 13 patients with residual lesions 24 h after APC demonstrated residual lesions at the three-month follow up. No post-procedural complications were observed. Conclusions Residual dysplasia may persist even after APC and cause local recurrence. If Ki-67-positive cells are detected in the remnant tissue following APC, additional interventions should be considered.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background: Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department. Methods: This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine).The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley’s additive explanations (SHAP). Results: Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756–0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626–0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results. Conclusion Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.