BACKGROUND/OBJECTIVES: Obesity is a complex metabolic disorder characterized by excessive adipose tissue accumulation, dysregulated lipid metabolism, and insulin resistance, leading to an increased risk of metabolic disease. While Withania somnifera (AS) and Chrysanthemum zawadskii Herbich var. latilobum (Maxim.) Kitamura (C) have traditionally been used for their metabolic regulatory properties, their combined effects on adipogenesis, lipogenesis, lipolysis, and insulin signaling remain unexplored. Therefore, this study aimed to evaluate the anti-obesity effects of AS, C, and their optimal combination (ASC) in 3T3-L1 adipocytes by investigating their impact on lipid metabolism and glucose homeostasis.MATERIALS/METHODS: Following adipogenic differentiation, 3T3-L1 adipocytes were treated with AS, C, and ASC at different concentrations. RESULTS: AS, C, and ASC significantly inhibited adipogenesis by downregulating cyclic adenosine monophosphate (cAMP) response element-binding protein, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding proteins alpha and beta phosphorylation, thereby reducing lipid accumulation in adipocytes. They also suppressed lipogenesis by downregulating the expression of dephosphorylated acetyl-CoA carboxylase, fatty acid synthase, and lipoprotein lipase. In contrast, they markedly enhanced lipolysis, as evidenced by increased hormone-sensitive lipase and protein kinase A expression, along with elevated glycerol release and cAMP levels. Furthermore, AS, C, and ASC activated energy metabolism pathways, as indicated by the upregulation of AMP-activated protein kinase, uncoupling protein 1, and carnitine palmitoyltransferase 1A, suggesting a transition toward enhanced mitochondrial fatty acid oxidation. Notably, AS, C, and ASC significantly improved insulin signaling by restoring insulin receptor substrate 1, phosphoinositide 3-kinase, and Akt phosphorylation, while upregulating glucose transporter type 4 expression, indicating enhanced glucose uptake. Among all treatments, ASC showed relatively greater efficacy compared to AS or C alone, suggesting a potential additive effect. CONCLUSION These findings demonstrate that ASC effectively modulates multiple metabolic pathways in adipocytes, including adipogenesis, lipogenesis, lipolysis, energy metabolism, and insulin signaling, to exert its anti-obesity effects.

Maternally inherited diabetes and deafness (MIDD) is a rare mitochondrial disorder primarily resulting from m.3243A>G mutation. The clinical characteristics of MIDD exhibit significant heterogeneity. Our study aims to delineate these characteristics and determine the potential correlation with m.3243A>G heteroplasmy levels. This retrospective, descriptive study encompassed patients with confirmed m.3243A>G mutation and diabetes mellitus at Seoul National University Hospital. Our cohort comprises 40 patients with MIDD, with a mean age at study enrollment of 33.3±12.9 years and an average % of heteroplasmy of 30.0%± 14.6% in the peripheral blood. The most prevalent comorbidity was hearing loss (90%), followed by albuminuria (61%), seizure (38%), and stroke (33%). We observed a significant negative correlation between % of heteroplasmy and age at diabetes diagnosis. These clinical features can aid in the suspicion of MIDD and further consideration of genetic testing for m.3243A>G mutation.

Background: We sought to identify prognostic risk factors for one year recurrence in patient with renal cell carcinoma (RCC) after partial or radical nephrectomy. Methods: We performed a retrospective study of 1,269 patients with RCC after partial or radical nephrectomy and diagnosed recurrence using Korean Renal Cancer Study Group (KRoCS) database between January 1991 and March 2017. Recurrence-free survival (RFS), and overall survival (OS) were calculated using the Kaplan–Meier method and multivariate Cox regression analysis were performed to evaluate independent prognostic factors for recurrence. Results: The median patient age was 56 years and median follow-up period was 67 months.Multivariable analysis demonstrated BMI greater than or equal to 23 and less than 30 (vs. BMI less than 23, hazard ratio [HR]: 0.707, P = 0.020) reduced recurrence one year postoperatively. Eastern Cooperative Oncology Group performance status (ECOG PS) greater than or equal to 1 (vs. ECOG PS 0, HR: 1.548, P = 0.007), high pathological T stage (pT2 vs.pT1, HR: 2.622, P < 0.001; pT3 vs. pT1, HR: 4.256, P < 0.001; pT4 vs. pT1, HR: 4.558, P < 0.001), and tumor necrosis (vs. no tumor necrosis, HR: 2.822, P < 0.001) were independent predictive factors for early recurrence within one year in patients with RCC. Statistically significant differences on RFS and OS were found among pathological T stages (pT2 vs. pT1; pT3 vs. pT1; pT4 vs. pT1, all P < 0.001). Conclusion This large multicenter study demonstrated ECOG PS greater than or equal to 1, high pathological T stage, tumor necrosis and BMI less than 23 were significant prognostic risk factors of early recurrence within one year in patients with RCC who underwent nephrectomy.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Purpose: This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). Materials and Methods: A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups. Results: No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups. Conclusions ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.

Background: In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC. Methods: This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed. Results: A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months). Conclusion In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.

Background: In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC. Methods: This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed. Results: A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months). Conclusion In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.

Background: In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC. Methods: This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed. Results: A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months). Conclusion In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.

Background: In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC. Methods: This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed. Results: A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1–6). The median age at the initiation of systemic therapy was 60 years (IQR, 29–88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months). Conclusion In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.

Purpose: We conducted a randomized prospective trial (KLASS-07 trial) to compare laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. In this interim report, we describe short-term results in terms of morbidity and mortality. Methods: and Methods: The sample size was 442 participants. At the time of the interim analysis, 314 patients were enrolled and randomized. After excluding patients who did not undergo planned surgeries, we performed a modified per-protocol analysis of 151 and 145 patients in the LADG and TLDG groups, respectively. Results: The baseline characteristics, including comorbidity status, did not differ between the LADG and TLDG groups. Blood loss was somewhat higher in the LADG group, but statistical significance was not attained (76.76±72.63 vs. 62.91±65.68 mL; P=0.087). Neither the required transfusion level nor the operation or reconstruction time differed between the 2 groups. The mini-laparotomy incision in the LADG group was significantly longer than the extended umbilical incision required for specimen removal in the TLDG group (4.79±0.82 vs. 3.89±0.83 cm; P<0.001). There were no between-group differences in the time to solid food intake, hospital stay, pain score, or complications within 30 days postoperatively. No mortality was observed in either group. Conclusions Short-term morbidity and mortality rates did not differ between the LADG and TLDG groups. The KLASS-07 trial is currently underway.