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Purpose: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. Materials and Methods: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan–Meier method was used to assess treatment outcomes. Results: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. Conclusions PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.

Purpose: To identify changes in prostate cancer (PCa) risk-stratification during the last two decades in Korea, where the social perception of PCa was limited due to a relatively low incidence but has recently been triggered by the rapidly increasing incidence of benign prostate hyperplasia. Materials and Methods: Retrospective data of patients who had received a diagnosis of PCa in a single Korean province (Daegu-Gyeongsangbuk) at all seven training hospitals in the years 2003, 2007, 2011, 2015, 2019, and 2021 were subjected to analysis. Changes in PCa risk-stratification were investigated with respect to serum prostate-specific antigen (PSA), Gleason score (GS), and clinical stage. Results: Of the 3,393 study subjects that received a diagnosis of PCa, 64.1% had high-risk disease, 23.0% intermediate, and 12.9% low-risk disease. The proportion diagnosed with high-risk disease was 54.8% in 2003, 30.6% in 2019, but then increased to 35.1% in 2021. The proportion of patients with high PSA (>20 ng/mL) steadily decreased from 59.4% in 2003 to 29.6% in 2021, whereas the proportion with a high GS (>8) increased from 32.8% in 2011 to 34.0% in 2021, and the proportion with advanced stage disease (over cT2c) increased from 26.5% in 2011 to 37.1% in 2021. Conclusions: In this retrospective study, conducted in a single Korean province, high-risk PCa accounted for the largest proportion of newly registered Korean PCa patients during the last two decades and increased in the early 2020s. This outcome supports the adoption of nationwide PSA screening, regardless of current Western guidelines.

Purpose: This study aimed to compare the characteristics of asymptomatic and symptomatic nephrolithiasis in patients who underwent surgical treatment for kidney stones. Materials and Methods: Between 2015 and 2019, 245 patients who underwent percutaneous nephrolithotomy or retrograde intrarenal surgery for kidney stones were included. The patients were divided into asymptomatic (n=124) and symptomatic (n=121) groups. All patients underwent blood and urine tests, preoperative non-contrast computed tomography, and postoperative stone composition analysis. We retrospectively analyzed and compared the characteristics of the patients and stones, operation time, stone-free rate, and postoperative complications between the two groups. Results: In the asymptomatic group, mean body mass index (BMI) was significantly higher (25.7±3.8 kg/m2 vs. 24.3±2.8 kg/m2, p=0.002) and urine pH was significantly lower (5.6±0.9 vs. 5.9±0.9, p=0.013). The ratio of calcium oxalate dihydrate stones was significantly higher in the symptomatic group (5.3% vs. 15.5%, p=0.023). No significant differences were observed in stone characteristics, postoperative outcomes, or complications. In the multivariate logistic regression analysis for predicting variables for asymptomatic renal stones, BMI (odds ratio [OR], 1.144; 95% confidence interval [CI], 1.038–1.260; p=0.007), and urine pH (OR, 0.608; 95% CI, 0.407–0.910; p=0.016) were independent predictive variables for asymptomatic renal stones. Conclusions: This study demonstrated that thorough medical check-ups are needed for the early detection of renal stones in individuals with a high BMI or low urine pH.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

Due to the short storage period, large quantities of platelet concentrate (PC) are expiring. The expired PC cannot be injected into a blood vessel, but the activity of bioactive molecules, especially growth factors, is still preserved. In this paper, we organized a process to obtain a growth factor-rich bioproduct for use as a supplement in human cell culture by optimizing freezing, thawing, and sterilization conditions. Each unit of PC displayed visual differences, diverse biochemical values, and growth factor concentrations. To minimize lot-to-lot variation, we pooled a minimum of 10 PC units. The concentrations of growth factors were maximized through five freeze–thaw cycles for 12 h at −80 °C for freezing and for 5 min at 36 °C for thawing. We used a cell strainer with 40 µm pores, followed by a 0.45 μm filter and a 0.22 μm filter sequentially to sterilize the bioproduct with minimizing loss. The obtained growth factors remained stable for 4–6 h at room temperature (23 °C), 24 h at 4 °C, and 12 months at −80 °C. Cellular responses to the growth factor-rich bioproduct were tested with primary human renal proximal tubule epithelial cells. The cells exhibited a significantly increased growth rate, compared to the fetal bovine serum (FBS)-treated control group. The cells maintained their characteristic cuboidal shape, and stem cells and renal progenitor cells also preserved their genetic characteristics during culture. Therefore, the growth factor-rich bioproduct isolated from expired PC through our process can be used as a medium supplement to replace FBS in human cell culture for clinical application.

Targeted protein degradation is a promising approach for basic research and therapeutic applications. Here, the authors develop a targeted protein degradation platform called AUTOTAC to degrade oncoproteins and neurodegeneration-associated proteins via the p62-dependent autophagy-lysosome system.

Ulcerative colitis is an inflammatory bowel disease characterized by inflammation in the mucosal and submucosal layers of the colon. Obesity is closely related to the occurrence and progression of colitis. The most plausible mechanism linking obesity and colitis is an excessive adipogenesis-related inflammatory response, which causes mucosal dysfunction. Obesity and colitis are linked by several etiologic mechanisms, including excessive adipogenesis, lipotoxicity, pro-inflammatory adipokines/cytokines, macrophage polarization, oxidative stress, endoplasmic reticulum (ER) stress, and gut microbiota. These low-grade enteric inflammations cause mucosal layer damage, especially goblet cell dysfunction through mucin 2 (MUC2) misfolding, ultimately leading to colitis. Inhibiting the inflammatory response can be the most effective approach for treating obesity-related colitis. We focused on the anti-inflammatory effects of polyphenols in Protaectia brevitas larvae. The P. brevitas was prepared as a low molecular protein hydrolysate (PHPB) to increase the concentration of anti-inflammatory molecules. In the current study, we investigated the anti-inflammatory effect of PHPB in an obesity-induced colitis mouse model. Compared with the high-fat diet (HFD) group, the group treated with PHPB exhibited reduced body/organ/fat weight, appetite/food intake inhibition, hypolipidemic effect on ectopic fat, and anti-adipogenic mechanism through the AMPK signaling pathway. Furthermore, we observed attenuated expression of PPARγ and C/EBPα, inhibition of pro-inflammatory molecules, stimulation of anti-inflammatory molecules, probiotic-like effect against obesogenic gut microbiota, inhibition of macrophage polarization into M1, suppression of oxidative/ER stress, and reduction of Muc2 protein misfolding in colon. These diverse anti-inflammatory responses caused histological and functional recovery of goblet cells, eventually improving colitis. Therefore, our findings suggest that the protein hydrolysate of Protaetia brevitarsis can improve obesity-related colitis through its anti-inflammatory activities.

The complete mitochondrial genome of a Korean endemic species, Iksookimia pacifica (Teleostei: Cypriniformes: Cobitidae) was sequenced using the NGS method. Its total mitogenome was 16,561 bp in length, comprising 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNA), 22 transfer RNA genes (tRNA), and 1 control region (D-loop). The gene order and content were congruent with those of other cobitid species. In the phylogenetic tree using the maximum likelihood method, I. pacifica was clearly distinguished and most closely related to I. koreensis. The mitogenome sequence data of I. pacifica will provide useful information on the phylogenetic relationship among Cobitidae species.

Background We aimed to analyze the effectiveness of albumin to globulin ratio (AGR) in predicting postoperative febrile urinary tract infection (fUTI) after ureteroscopic lithotripsy (URS) and retrograde intrarenal surgery (RIRS). Methods From January 2013 to May 2018, 332 patients underwent URS and RIRS. The rate of postoperative fUTI and risk factors for postoperative fUTI were analyzed using logistic regression. Patients were divided into postoperative fUTI and non-postoperative fUTI (non-fUTI) groups. AGR with other demographic and perioperative data were compared between the two groups to predict the development of fUTI after URS. Results Of the 332 patients, postoperative fUTI occurred in 41 (12.3%). Preoperative pyuria, microscopic hematuria, diabetes mellitus, hypoalbuminemia, and hyperglobulinemia were more prevalent in the fUTI group. Patients in the fUTI group had larger stone size, lower preoperative AGR, longer operation time, and longer preoperative antibiotic coverage period. In a multivariable logistic analysis, preoperative pyuria, AGR, and stone size were independently correlated with postoperative fUTI (p

Abstract The olfactory organs of two African lungfishes, Protopterus amphibius and P. dolloi, were investigated using a stereo microscope and a compound light microscope and were described anatomically, histologically, and histochemically. Like other lungfishes, these species present the following general features: i) elongated olfactory chamber (OC), ii) anterior nostril at the ventral tip of the upper lip, iii) posterior nostril on the palate of the oral cavity, iv) lamellae with multiple cell types such as olfactory receptor neurons, supporting cells, basal cells, lymphatic cells, and mucous cells (MC), and vi) vomero-like epithelial crypt (VEC) made of glandular epithelium (GE) and crypt sensory epithelium. Some of these features exhibit differences between species: MCs are abundant in both the lamellar and inner walls of the OC in P. amphibius but occur only in lamellae in P. dolloi. On the other hand, some between feature differences are consistent across species: the GE of both P. amphibius and P. dolloi is strongly positive for Alcian blue (pH 2.5)-periodic acid Schiff (deep violet coloration), and positive with hematoxylin and eosin and with Masson’s trichrome (reddish-brown staining), unlike the MCs of the two species which stain dark red with both Alcian blue (pH 2.5)-periodic acid Schiff and Masson’s trichrome but respond faintly to hematoxylin and eosin. The differing abundance of MCs in the two lungfishes might reflect different degrees in aerial exposure of the olfactory organ, while the neutral and acid mucopolysaccharide-containing VEC, as indicated by staining properties of the MCs, is evolutionary evidence that P. amphibius and P. dolloi are the closest living relatives to tetrapods, at least in the order Dipnoi.

Purpose: The purpose of this study was to evaluate end-of-life resource utilization and costs for prostate cancer patients during the last year of life in Korea. Materials and Methods: The study used the National Health Information Database (NHIS-2017-4-031) of the Korean National Health Insurance Service. Healthcare claim data for the years 2002 through 2015 were collected from the Korean National Health Insurance System. Among 83,173 prostate cancer patients, we enrolled 18,419 after excluding 1,082 who never claimed for the last year of life. Results: From 2006 to 2015, there was a 3.2-fold increase the total number of prostate cancer decedents. The average cost of care during the last year of life increased over the 10-year period, from 14,420,000 Korean won to 20,300,000 Korean won, regardless of survival time. The cost of major treatments and medications, other than analgesics, was relatively high. Radiologic tests, opioids, pain control, and rehabilitation costs were relatively low. Multiple regression analysis identified age and living in rural area as negatively associated with prostate cancer care costs, whereas income level and a higher number of comorbidities were positively associated. Conclusions: Expenditure of prostate cancer care during the last year of life varied according to patient characteristics. Average costs increased every year. However, the results suggest underutilization of support services, likely due to lack of alternative accommodation for terminal prostate cancer patients. Further examination of patterns of utilization of healthcare resources will allow policymakers to take a better approach to reducing the burden of prostate cancer care.

Purpose: Perirenal fat stranding (PRFS) is defined as linear areas of soft-tissue attenuation in the perirenal space that can result from ureteral obstruction. We analyzed the prognostic impact of PRFS on outcomes in patients with ureteral urothelial carcinoma (UC). Materials and Methods: Overall, 126 patients evaluated preoperatively by computerized tomography (CT) scan and diagnosed with ureteral UC following nephroureterectomy between January 2001 and May 2018 were included. We analyzed associations between oncologic outcomes and secondary signs such as hydronephrosis and PRFS. Results: Overall, 68 patients (54.0%) showed PRFS on preoperative CT scans. The patients' mean age was 66.33±9.49 years. A high pT stage (≥T3) was seen in 47 patients (37.3%) and high-grade tumors were seen in 90 patients (71.4%). Lymphovascular invasion (LVI) was seen in 15 patients (11.9%), and 5 (4.0%) were at the pN1 stage. Multivariate Cox analysis showed that cT stage≥3, PRFS, pT stage≥3, tumor grade, LVI, and pN1 stage were independent prognostic factors of recurrence-free survival (RFS) and cancer-specific survival (CSS) (all p

Abstract Background Febrile urinary tract infection (UTI) is one of the most common complications after ureteroscopic lithotripsy (URS). We evaluated the effect of secondary signs on preoperative computed tomography (CT) for febrile UTI after URS. Methods In total, 182 patients who underwent URS for ureteral stones from January 2013 to December 2015 were retrospectively included in this study. These patients were divided into two groups according to the presence of postoperative febrile UTI after URS. We compared the clinical factors, stone factors, and secondary signs between the groups. Predictive factors for febrile UTI after URS were analyzed using a multivariate logistic regression model. Results Febrile UTI occurred in 26 of the 182 patients. In univariate analysis, presence of comorbid chronic kidney disease (CKD) and stone size were significantly different between UTI and non-UTI groups. Among secondary signs, presence of hydroureter, perinephric fat stranding, periureteral fat stranding, and tissue rim sign were significantly different between the groups. In multivariate logistic regression analysis, comorbid CKD, stone size, perinephric fat stranding, and tissue rim sign were independent predictive factors for febrile UTI after URS. Conclusion This study demonstrated that secondary signs including perinephric fat stranding and tissue rim sign on preoperative CT, CKD, and stone size are independent predictive factors for febrile UTI after URS.

Purpose: The purpose of this study was to determine the comparative effectiveness of androgen deprivation therapy (ADT) combined with docetaxel (DTX)-based chemotherapy in Korean and Japanese castration-resistant prostate cancer (CRPC) patient cohorts. Materials and Methods: Metastatic CRPC patients who underwent more than three DTX-based chemotherapy cycles in Korea and Japan between 2002 and 2017 were retrospectively analyzed and divided into the DTX-only (DTX, n=30) and combination (DTX+ADT, n=46) groups. Progression-free survival (PFS) was calculated as the time from the start of chemotherapy to the occurrence of either disease progression (prostate-specific antigen [PSA] progression or radiographic progression) or death. The primary end point was PFS and the secondary end point was overall survival (OS). Results: In the DTX and DTX+ADT groups, the median PFS was 6.0 and 11.0 months (log-rank p=0.053). The multivariate Cox regression analysis revealed that the significant predicting factors of PFS were ADT administration (hazard ratio [HR], 0.478; 95% confidence interval [CI], 0.284–0.804; p=0.005) and number of DTX-based chemotherapy cycles (HR, 0.934; 95% CI, 0.899–0.970; p

Objective To evaluate the prognostic factors associated with the sustained return of spontaneous circulation (ROSC) and survival to hospital discharge in traumatic out-of-hospital cardiac arrest (TOHCA) patients without prehospital ROSC. Methods We analyzed Korean nationwide data from the Out-of-Hospital Cardiac Arrest Surveillance, and included adult TOHCA patients without prehospital ROSC from January 2012 to December 2016. The primary outcome was sustained ROSC (>20 minutes). The secondary outcome was survival to discharge. Multivariate analysis was performed to investigate factors associated with the outcomes of TOHCA patients. Results Among 142,905 cases of OHCA, 8,326 TOHCA patients were investigated. In multivariate analysis, male sex (odds ratio [OR], 1.326; 95% confidence interval [CI], 1.103–1.594; P=0.003), and an initial shockable rhythm (OR, 1.956; 95% CI, 1.113–3.439; P=0.020) were significantly associated with sustained ROSC. Compared with traffic crash, collision (OR, 1.448; 95% CI, 1.086–1.930; P=0.012) was associated with sustained ROSC. Fall (OR, 0.723; 95% CI, 0.589–0.888; P=0.002) was inversely associated with sustained ROSC. Male sex (OR, 1.457; 95% CI, 1.026–2.069; P=0.035) and an initial shockable rhythm (OR, 4.724; 95% CI, 2.451–9.106; P

Abstract The detailed anatomy, ultrastructure and histology of the olfactory organ of Micropterus salmoides were investigated by a stereo microscope, a light microscope, and a scanning electron microscope. Its external structure shows a tube-like anterior nostril to stick out and a posterior nostril flat to the skin surface. Meanwhile, its internal structure, the olfactory chamber, contains a fan-shaped rosette structure with 9 to 11 lamellae in adult fish over 35 cm in standard length (SL) and two accessory nasal sacs (ethmoidal and lacrimal sacs) were found. Interestingly, the rosette in young fish under 15 cm in SL was a longitudinal structure in parallel with each of 4–5 lamellae. Histologically, the sensory epithelium (SE) on the olfactory chamber consists of 5 types of cells: olfactory receptor neurons, supporting cells, basal cells, lymphatic cells and mucous cells. In contrast, the non-sensory epithelium (NSE) has stratified epithelial cells, lymphatic cells and mucous cells. The mucous cells of the SE are abundant and distributed densely in one row on the outermost superficial surface, but the one of the NSE are less than the SE. From these results, the olfactory characters of M. salmoides may be related with its ecological habit spending in the middle layer of stagnant water contaminated, more or less.

Purpose: We evaluated factors predicting a positive repeat biopsy result in patients with an initial negative prostate biopsy result. Materials and Methods: This study included 124 patients in whom prostate cancer (PCa) was not detected in the initial transrectal ultrasound-guided prostate biopsy and who underwent repeat biopsy from January 2011 to December 2017. Patients without PCa in both initial and repeat prostate biopsies were designated as group 1 (n=82), and those in whom PCa was detected on a repeat prostate biopsy were designated as group 2 (n=42). Among group 2 patients, 6 had insignificant PCa according to the Epstein criteria and were combined with group 1 patients to make up group A (n=88). Patients with significant PCa were categorized as group B (n=36). We compared clinicopathologic characteristics between the groups. Results: Multivariate analysis showed that age (p=0.018) and detection of atypical small acinar proliferation (ASAP) or ≥3 cores of high-grade prostatic intraepithelial neoplasia (HGPIN) (p=0.011) on the initial biopsy were predictive factors for a positive result on a repeat biopsy. When we compared group A and group B, age (p=0.004) and the De Ritis ratio (p=0.024) were significantly higher in group B in the multivariate analysis. Conclusions: Age and the detection of ASAP or ≥3 cores of HGPIN on the initial biopsy were associated with detection of PCa on a repeat biopsy. Age and the De Ritis ratio were found to be predictive factors for the detection of clinically significant PCa on a repeat biopsy.

No definitive criteria regarding the performance of preoperative chest computed tomography (CT) in patients with cT1a renal cell carcinoma (RCC) exists. We aimed to establish an objective standard for the optimal timing of preoperative chest CT in patients with RCC. Data from 890 patients who underwent surgical treatment for RCC between January 2011 and December 2020 were retrospectively collected. The primary endpoint was detection of lung metastasis on chest CT before nephrectomy. A multivariable logistic regression model predicting positive chest CT scans was used. Predictors included preoperative cTN stage, presence of systemic symptoms, Charlson comorbidity index (CCI), platelet count/hemoglobin ratio, albumin/globulin ratio (AGR), and De Ritis ratio. The overall rate of positive chest CT scans before nephrectomy was 3.03% (27/890). Only one patient had lung metastasis before surgery for cT1a. cT stage (≥cT1b), CCI ≥4, and low AGR were associated with a higher risk of positive chest CT scans. The best cutoff value for AGR was 1.39. After 890-sample bootstrap validation, the concordance index was 0.80. The net benefit of the proposed strategy was superior to that of the select-all and select-none strategies according to decision curve analysis. Therefore, when chest CT scans were performed with a risk of a positive result ≥10%, 532 (59.8%) negative chest CT scans could be prevented. Only 24 (2.7%) potentially positive chest CT scans were misdiagnosed. Therefore, we recommend chest CT in patients with ≥cT1b disease, CCI ≥4, and low AGR.

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.

Abstract Background New biological prognostic predictors have been studied; however, some factors have limited clinical application due to tissue-specific expression and high cost. There is the need for a promising predictive factor that is simple to detect and that is closely linked to oncological outcomes in patients with urothelial bladder cancer (BC) who have undergone radical cystectomy (RC). Therefore, we investigated the clinical prognostic value of the preoperative De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) on oncological outcomes in patients with urothelial BC after RC. Methods We retrospectively evaluated clinicopathological data of 118 patients with non-metastatic urothelial BC after RC between 2008 and 2013 at a single center. The association between the De Ritis ratio and clinicopathological findings was assessed. The potential prognostic value of the De Ritis ratio was analyzed using the Kaplan-Meier method, and multivariate Cox analyses were performed to identify the independent predictors of metastasis-free survival, cancer-specific survival, and overall survival. Results According to the receiver operating curve of the De Ritis ratio for metastasis, we stratified the patients into 2 groups using a threshold of 1.3. A high De Ritis ratio was more likely to be associated with old age and the female sex. Kaplan-Meier estimates revealed that patients with a high De Ritis ratio had inferior metastasis-free survival, cancer-specific survival, and overall survival outcomes (P = 0.012, 0.024, and 0.022, respectively). Multivariate analysis revealed that a high De Ritis ratio was an independent prognostic factor for metastasis (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.161–4.914; P = 0.018), cancer-related death (HR, 2.755; 95% CI, 1.214–6.249; P = 0.015), and overall death (HR, 2.761; 95% CI, 1.257–6.067; P = 0.011). Conclusions An elevated De Ritis ratio was significantly associated with worse prognosis in patients who underwent RC for urothelial BC. This ratio might further improve the predictive accuracy for prognosis in BC.

The human body contains a variety of microbes. The distribution of microbes varies from organ to organ. Sequencing and bioinformatics techniques have revolutionized microbial research. Although previously considered to be sterile, the urinary bladder contains various microbes. Several studies have used urine and bladder tissues to reveal the microbiome of the urinary bladder. Lactic acid-producing bacteria, such as Bifidobacterium, Lactobacillus, and Lactococcus, are particularly beneficial for human health and are linked to bladder cancer. This review highlights the analysis protocols for microbiome research, the studies undertaken to date, and the microbes with therapeutic potential in bladder cancer.

Background: Prostate cancer is the second most common cause of cancer related death in males worldwide. Most patients show no response to androgen deprivation therapy in case of recurrence and proceed to advanced stage with metastasis. TRPM7 is reported to be upregulated in diverse types of tumors. Methods: We analyzed the expression of TRPM7 and related proteins by Western blotting analysis. We performed cell migration and invasion assay to analyze the relationship between tumor aggressiveness and TRPM7. In addition, we proceeded an animal study by using stable TRPM7 knockdown cell line in xenograft. Results: In our results, TRPM7 regulates prostate cancer cell biology including proliferation, migration and invasion through ERK1/2, PI3K/Akt and JNK signaling pathways. We produced stable TRPM7 knockdown prostate cancer cell line. To analyze the relationship between TRPM7 and tumorigenesis, we proceeded migration and invasion assay as well as xenograft model. TRPM7 down-regulated DU145 cells showed suppressed migratory and invasion ability, 0.65- and 0.05-fold, respectively. In addition, we confirmed that the anti-cancer effect of TRPM7 is mediated through inactivation of ERK1/2, Src and Akt signaling pathways by western blotting analysis. P-ERK1/2, p-Src, and p-Akt expressions were reduced to 0.66-, 0.68-, and 0.66-fold, respectively. Moreover, we treated ERK, Akt and Src inhibitors to clarify the involvement of related each protein in migration and invasion ability, and we could observe that inhibitor treated cells showed suppressed migration and invasion ability. In vivo, TRPM7 knockdown cells projected decreased cell proliferation rate. Conclusions: Taken these results together, out study suggested TRPM7 might be an essential gene for prostate cancer metastasis by regulating prostate cancer cell proliferation, migration and invasion ability.

Background To evaluate mid-term oncological and functional outcomes in patients with prostate cancer treated by robot-assisted laparoscopic radical prostatectomy (RALP) at our institution. Methods We retrospectively reviewed the medical records of 128 patients with prostate cancer who underwent RALP at our institution between February 2008 and April 2010. All patients enrolled in this study were followed up for at least 5 years. We analyzed biochemical recurrence (BCR)-free survival using a Kaplan-Meier survival curve analysis and predictive factors for BCR using multivariate Cox regression analysis. Continence recovery rate, defined as no use of urinary pads, was also evaluated. Results Based on the D’Amico risk classification, there were 30 low-risk patients (23.4%), 47 intermediate-risk patients (38.8%), and 51 high-risk patients (39.8%), preoperatively. Based on pathological findings, 50.0% of patients (64/128) showed non-organ confined disease (≥T3a) and 26.6% (34/128) had high grade disease (Gleason score ≥8). During a median follow-up period of 71 months (range, 66-78 months), the frequency of BCR was 33.6% (43/128) and the median BCR-free survival was 65.9 (0.4-88.0) months. Multivariate Cox regression analysis revealed that high grade disease (Gleason score ≥8) was an independent predictor for BCR (hazard ratio=4.180, 95% confidence interval=1.02-17.12, p=0.047). In addition, a majority of patients remained continent following the RALP procedure, without the need for additional intervention for post-prostatectomy incontinence. Conclusion Our study demonstrated acceptable outcomes following an initial RALP procedure, despite 50% of the patients investigated demonstrating high-risk features associated with non-organ confined disease.

ObjectiveThis prospective study sought to clarify the developmental endothelial locus-1 (Del-1) protein as values of diagnosis and risk stratification of prostate cancer (PCa).DesignFrom February 2017 to December 2019, a total 458 patients who underwent transrectal ultrasound guided prostate biopsy or surgery of benign prostatic hyperplasia agreed to research of Del-1 protein. We prospectively compared and analyzed the Del-1 protein and prostate specific antigen (PSA) in relation to the patients' demographic and clinicopathological characteristics.ResultsMean age was 68.86±8.55 years. Mean PSA and Del-1 protein was 21.72±89.37, 0.099±0.145, respectively. Two hundred seventy-six (60.3%) patients were diagnosed as PCa. Among them, 181 patients underwent radical prostatectomy (RP). There were significant differences in Del-1 protein between benign and PCa group (0.066±0.131 vs 0.121±0.149, respectively, pConclusionPatients with PCa showed higher expression of Del-1 protein than benign patients. Del-1 protein increased with the stage and Gleason score of PCa. Collaboration with PSA, Del-1 protein can be a non-invasive useful marker for diagnosis and risk stratification of PCa.

Advanced prostate cancer (PCa) patients with bone metastases are treated with androgen pathway directed therapy (APDT). However, this treatment invariably fails and the cancer becomes castration resistant. To elucidate resistance mechanisms and to provide a more predictive pre-clinical research platform reflecting tumor heterogeneity, we established organoids from a patient-derived xenograft (PDX) model of bone metastatic prostate cancer, PCSD1. APDT-resistant PDX-derived organoids (PDOs) emerged when cultured without androgen or with the anti-androgen, enzalutamide. Transcriptomics revealed up-regulation of neurogenic and steroidogenic genes and down-regulation of DNA repair, cell cycle, circadian pathways and the severe acute respiratory syndrome (SARS)-CoV-2 host viral entry factors, ACE2 and TMPRSS2. Time course analysis of the cell cycle in live cells revealed that enzalutamide induced a gradual transition into a reversible dormant state as shown here for the first time at the single cell level in the context of multi-cellular, 3D living organoids using the Fucci2BL fluorescent live cell cycle tracker system. We show here a new mechanism of castration resistance in which enzalutamide induced dormancy and novel basal-luminal-like cells in bone metastatic prostate cancer organoids. These PDX organoids can be used to develop therapies targeting dormant APDT-resistant cells and host factors required for SARS-CoV-2 viral entry.

Perirenal adipose tissue, one of the fat masses surrounding the kidneys, can be obtained from healthy donors during a kidney transplant. Perirenal adipose tissue has only ever been known as a connective tissue to protect the kidneys and renal blood vessels from external physical stimulation. Yet, recently, as adipose tissue has begun to be considered an endocrine organ, and perirenal adipose tissue is now regarded to have a direct effect on metabolic diseases. The characteristics of perirenal adipose tissue from a healthy donor are that: (1) There are a large number of brown adipose cells (70–80% of the total), (2) Most of the brown adipose cells are inactive in the resting cell cycle, (3) Activating factors are constant low-temperature exposure, hormones, metastasis factors, and environmental factors, (4) Anatomically, a large number of brown adipose cells are distributed close to the adrenal glands, (5) Beige cells, produced by converting white adipocytes to brown-like adipocytes, are highly active, (6) Activated cells secrete BATokines, and (7) Energy consumption efficiency is high. Despite these advantages, all of the perirenal adipose tissue from a healthy donor is incinerated as medical waste. With a view to its use, this review discusses the brown adipocytes and beige cells in perirenal adipose tissue from a healthy donor, and proposes opportunities for their clinical application.

In this study, we developed the portable chemiluminescence (CL)-based lateral flow assay (LFA) platform for the detection of cortisol in human serum. Cortisol is well-known as a stress hormone due to its high relevancy for human mental and physical health, such as hypertension or depression. To date, a number of optical devices have provided the sensitive determination of levels of analytes. However, this modality type still requires costly optical modules. The developed CL platform is simply composed of two detection modules along with a loading part for the LFA strip. The LFA membrane contains gold nanoparticle probes conjugated with antibodies against cortisol and horseradish peroxidase (HRP), which can also efficiently increase the luminescent signal by providing many areas for anti-cortisol antibody and HRP. The measured voltage signals coming from the photodiode in a CL reader were compared with a standard microplate reader for the evaluation of accuracy. The linear range observed for cortisol was measured to be 0.78–12.5 μg/dL (R2 = 0.99) with a limit of detection (LOD) of 0.342 μg/dL. In addition, the CL-LFA reader showed a high correlation (R2 = 0.96) with the standard cortisol console (COBAS 8000, Roche), suggesting that our developed CL-based LFA platform can be usable in situ.

Abstract Survival of Clonorchis sinensis, a cause of human clonorchiasis, requires tegument proteins, which are localized to the tegumental outer surface membrane. These proteins play an important role in a host response and parasite survival. Thus, these proteins are interesting molecular targets for vaccine and drug development. Here, we have determined two crystal structures of the calmodulin like domain (amino acid [aa] positions 1–81) and dynein light chain (DLC)-like domain (aa 83–177) of a 20.8-kDa tegumental-allergen-like protein from Clonorchis sinensis (CsTAL3). The calmodulin like domain has two Ca2+-binding sites (named CB1 and CB2), but Ca2+ binds to only one site, CB1. The DLC-like domain has a dimeric conformation; the interface is formed mainly by hydrogen bonds between the main chain atoms. In addition, we have determined full-length structure of CsTAL3 in solution and showed the conformational change of CsTAL3 induced by Ca2+ ion binding using small-angle X-ray scattering analysis and molecular dynamics simulations. The Ca2+-bound form has a more extended conformation than the Ca2+-free from does. These structural and biochemical analyses will advance the understanding of the biology of this liver fluke and may contribute to our understanding of the molecular mechanism of calcium-responsive and tegumental-allergen-like proteins.

Purpose Currently, holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP) are the standard surgical procedures used to treat benign prostatic hyperplasia (BPH). Several recent studies have demonstrated that the surgical management of BPH in patients with detrusor underactivity (DU) can effectively improve voiding symptoms, but comparative data on the efficacy of HoLEP and TURP are insufficient. Therefore, we compared the short-term surgical outcomes of HoLEP and TURP in patients with DU. Methods From January 2010 to May 2015, 352 patients underwent HoLEP or TURP in procedures performed by a single surgeon. Of these patients, 56 patients with both BPH and DU were enrolled in this study (HoLEP, n=24; TURP, n=32). Surgical outcomes were retrospectively compared between the 2 groups. DU was defined as a detrusor pressure at maximal flow rate of

Abstract Background The aim of this study was to evaluate the adverse effects of allogeneic mesenchymal stem cells (MSCs) transplanted via intravenous infusion in dogs and examine their safety. We performed a retrospective analysis of various clinical assessments, including physical examination, blood tests, and radiographs, and monitored the formation of neoplasms during a 6-month follow-up period in 40 client-owned dogs that received intravenous infusion of adipose tissue-derived MSCs (AT-MSCs) for the treatment of various underlying diseases between 2012 and 2018. Results No significant adverse effects of MSC therapy were detected by clinical assessment, blood tests, or radiographic examination in the 6-month follow-up period after the first MSC treatment. Additionally no new neoplasms were observed during this period. Conclusions To our knowledge, this study is the first to evaluate the safety aspects (≥ 6 months) associated with intravenous allogeneic AT-MSC infusion. These results suggest that allogenic AT-MSC infusion could be a useful and relatively safe therapeutic approach in canines.

Purpose: Based on the experiences of our center, we sought to verify the necessity of actively removing stones during retrograde intrarenal surgery (RIRS) for the management of renal stones. Materials and Methods: From March 2010 to March 2015, 248 patients underwent RIRS at our center. We classified these patients into 2 groups according to the performance of active stone removal; group A (n=172) included the patients whose stones were actively removed using a stone basket, and group B (n=76) included the patients whose stones were fragmented with laser lithotripsy without active removal of the fragments. We retrospectively compared the operation time, success rate, and complication rate between the 2 groups. Results: There were no significant differences between groups A and B in terms of mean age (56.1 years vs. 58.6 years), male to female ratio (115:57 vs. 46:30), mean body mass index (24.5 kg/m2 vs. 25.0 kg/m2 ), mean preoperative size of stone (11.1 mm vs. 11.1 mm), the ratio of unilateral and bilateral stones (136:36 vs. 64:12), success rate (89.0% vs. 86.8%), operation time (82.5 minutes vs. 82.1 minutes), overall complication rate (9.9% vs. 11.8%), incidence of febrile urinary tract infection (6.4% vs. 2.6%), gross hematuria (1.7% vs. 2.6%), or postoperative de novo hydronephrosis (2.9% vs. 5.3%). Conclusions: This study demonstrated that during RIRS, fragmentation only, without the active removal of stones, is a safe and effective technique in which the surgical outcomes are comparable to those of procedures involving the active removal of stones.

Purpose: The aim of this study was to assess the advantages of robotic surgery, comparing perioperative and oncological outcomes between robot-assisted radical cystectomy (RARC) and open radical cystectomy (ORC). Materials and Methods: Between August 2008 and May 2014, 112 radical cystectomies (42 RARCs and 70 ORCs) were performed at a single academic institution following Institutional Review Board approval. Patient demographics, perioperative variables (e.g., complications), and oncologic outcomes including metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were reported using the Kaplan-Meier analyses. Results: The median follow-up period was 40 months (range, 0–70 months) vs. 42 months (range, 0–74 months) in RARC and ORC, respectively. Baseline characteristics of both groups were balanced. Blood loss (median, [range]; 300 mL [125–925 mL] vs. 598 mL [150–2,000 mL], p=0.001) and perioperative transfusion rates (23.8% vs. 45.7%, p=0.020) were significantly lower in the RARC group than in the ORC group. The overall complication rates were greater in the ORC group, but this was not statistically significant (65.7% vs. 64.3%, p=0.878). However, there were significantly higher major complication rates in the ORC group (45.7% vs. 26.2%, p=0.040). No significant differences were found with regards to MFS, CSS, and OS. Conclusions: While histopathological findings, overall complications, and survival rates do not reveal definite differences, RARC has more advantages compared to ORC in terms of estimated blood loss, perioperative transfusion rates and fewer perioperative major complications. We propose that RARC is a safer treatment modality with equivalent oncological outcomes compared to ORC.

Purpose: We aimed to retrospectively evaluate the risk factors for hypertensive attack during adrenalectomy in patients with pheochromocytoma. Despite the development of newer surgical and anesthetic techniques for the management of pheochromocytoma, intraoperative hypertensive attack continues to present a challenge. Materials and Methods: Data from 53 patients diagnosed with pheochromocytoma at Kyungpook National Uriversity Medical Center between January 2000 and June 2012 were retrospectively analyzed. The subjects were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack. A univariate analysis was conducted, and a multivariate logistic regression analysis was also performed. Results: In the univariate analysis, systolic blood pressure at presentation, preoperative hormonal status (including epinephrine, norepinephrine, vanillylmandelic acid, and metanephrine levels in a 24-hour urine sample), tumor size, and postoperative systolic blood pressure were significantly associated with the development of hypertensive attack. In the multivariate analysis, preoperative epinephrine level and tumor size were independent factors that predicted hypertensive attack. The highest odds ratio for tumor size (2.169) was obtained at a cutoff value of 4.25 cm and the highest odds ratio for preoperative epinephrine (1.020) was obtained at a cutoff value of 166.3 μg/d. Conclusions: In this study, a large tumor size and an elevated preoperative urinary epinephrine level were risk factors for intraoperative hypertensive attack in patients with pheochromocytoma.

AIMS:To evaluate the relationships between open-angle glaucoma (OAG) and various anthropometric measurements. DESIGN:Korea National Health and Nutrition Examination Survey (KNHANES), a population-based cross-sectional study using a complex, stratified, multistage, probability-cluster survey. METHODS:A total of 5,255 participants including 247 glaucoma patients, aged ≥ 19 years were included from the KNHANES V database. Glaucoma diagnosis was based on International Society of Geographical and Epidemiological Ophthalmology criteria. Various anthropometric data regarding obesity were analyzed including body mass index (BMI), total body fat mass, total body muscle mass (lean body mass, non-bone lean body mass, and appendicular skeletal muscle (ASM) mass), and waist circumference (WC). The differences in OAG prevalence with respect to anthropometric parameter quartiles were examined. RESULTS:In males, the multivariate general linear model adjusted for age, alcohol, smoking, exercise, systemic hypertension, diabetes, and intraocular pressure (IOP) showed the quartiles for the anthropometric parameters BMI, fat mass/weight ratio and fat mass/muscle mass ratio were negatively associated with OAG. However, muscle mass parameter/BMI ratio was significantly positively associated with OAG (P for trend

DYON is a plasma initiation modelling code that solves the differential equation system of the full circuit equations (plasma current, active coil currents and eddy currents in full passive structures) and 0D global energy and particle balance equations (Kim 2022 Nucl. Fusion 62 126012). In order to test the capability of the full electromagnetic plasma initiation model to predict individual discharges in experiments and thus the operating space in the device, a dedicated experimental database was built in MAST-U by scanning the prefilled gas pressure p _0 and the induced loop voltage $V_{\mathrm{loop}}$ . In the experimental operating space of p _0 and $V_{\mathrm{loop}}$ the lower and the upper limits of p _0 are determined by the plasma breakdown failure and the plasma burn-through failure, respectively. The lower limit of $V_{\mathrm{loop}}$ is determined by the plasma burn-through failure. By directly reading the control room data used in each discharge (i.e. currents in the solenoid, poloidal field coils, and toroidal field coils, p _0 , and gas puffing rate), the full electromagnetic DYON consistently predicted the failed breakdown, failed burn-through, and successful plasma initiation discharges in the experimental database, demonstrating its capability to predict the operating space for inductive plasma initiation. The Paschen curve calculated with the effective connection length in MAST-U indicates a much higher p _0 required for plasma breakdown than the experimental data, indicating that individual field line evaluation is necessary to calculate the quantitative requirements for Townsend breakdown. The demonstration in this paper shows that the full electromagnetic DYON could be a useful simulation tool to assess the feasibility of inductive plasma initiation and to optimise operating scenarios in future devices.

JET experiments using the fuel mixture envisaged for fusion power plants, deuterium and tritium (D–T), provide a unique opportunity to validate existing D–T fusion power prediction capabilities in support of future device design and operation preparation. The 2021 JET D–T experimental campaign has achieved D–T fusion powers sustained over 5 s in ITER-relevant conditions i.e. operation with the baseline or hybrid scenario in the full metallic wall. In preparation of the 2021 JET D–T experimental campaign, extensive D–T predictive modelling was carried out with several assumptions based on D discharges. To improve the validity of ITER D–T predictive modelling in the future, it is important to use the input data measured from 2021 JET D–T discharges in the present core predictive modelling, and to specify the accuracy of the D–T fusion power prediction in comparison with the experiments. This paper reports on the validation of the core integrated modelling with TRANSP, JINTRAC, and ETS coupled with a quasilinear turbulent transport model (Trapped Gyro Landau Fluid or QualLiKiz) against the measured data in 2021 JET D–T discharges. Detailed simulation settings and the heating and transport models used are described. The D–T fusion power calculated with the interpretive TRANSP runs for 38 D–T discharges (12 baseline and 26 hybrid discharges) reproduced the measured values within 20 $\%$ . This indicates the additional uncertainties, that could result from the measurement error bars in kinetic profiles, impurity contents and neutron rates, and also from the beam-thermal fusion reaction modelling, are less than $20\%$ in total. The good statistical agreement confirms that we have the capability to accurately calculate the D–T fusion power if correct kinetic profiles are predicted, and indicates that any larger deviation of the D–T fusion power prediction from the measured fusion power could be attributed to the deviation of the predicted kinetic profiles from the measured kinetic profiles in these plasma scenarios. Without any posterior adjustment of the simulation settings, the ratio of predicted D–T fusion power to the measured fusion power was found as 65%–96% for the D–T baseline and 81%–97% for D–T hybrid discharge. Possible reasons for the lower D–T prediction are discussed and future works to improve the fusion power prediction capability are suggested. The D–T predictive modelling results have also been compared to the predictive modelling of the counterpart D discharges, where the key engineering parameters are similar. Features in the predicted kinetic profiles of D–T discharges such as underprediction of n _e are also found in the prediction results of the counterpart D discharges, and it leads to similar levels of the normalized neutron rate prediction between the modelling results of D–T and the counterpart D discharges. This implies that the credibility of D–T fusion power prediction could be a priori estimated by the prediction quality of the preparatory D discharges, which will be attempted before actual D–T experiments.

In South Korea, car insurance that includes medical coverage of traditional Korean medicine (TKM) has increased exponentially. Clinical practice guidelines (CPG) for traffic injuries were established in 2016. We aimed to revise and update de novo CPG and distribute the adapted CPG to TKM practitioners and patients. Clinical key questions from previous CPG were identified and updated regarding the grade of recommendation and level of evidence using additional evidence from the literature obtained through a systematic search and the use of the Grading of Recommendations Assessment, Development, and Evaluation methodology. The dissemination and implementation of the updated CPG were conducted at the CPG Center of Korean Medicine. Ultimately, 25 recommendations based on 13 clinical key questions were developed: 2 for diagnosis, 22 for TKM treatments, and 1 for prognosis. After recognition by professional societies and certification by the CPG Center of Korean Medicine, leaflets, card news, and infographics for TKM doctors in South Korea were produced and distributed. These are the only TKM CPG for patients who have experienced traffic injuries. They are expected to contribute to standardized and evidence-based treatment using TKM and similar interventions. Moreover, disseminating the adapted CPG will promote treatment reliability and strengthen insurance coverage.

Screening of high-Z (W) impurities from the confined plasma by the temperature gradient at the plasma periphery of fusion-grade H-mode plasmas has been demonstrated in the JET-ILW (ITER-like wall) tokamak. Through careful optimisation of the hybrid-scenario, deuterium plasmas with sufficient heating power ( $\gtrsim$ 32 MW), high enough ion temperature gradients at the H-mode pedestal top can be achieved for the collisional, neo-classical convection of the W impurities to be directed outwards, expelling them from the confined plasma. Measurements of the W impurity fluxes between and during edge-localised modes (ELMs) based on fast bolometry measurements show that in such plasmas there is a net efflux (loss) between ELMs but that ELMs often allow some W back into the confined plasma. Provided steady, high-power heating is maintained, this mechanism allows such plasmas to sustain high performance, with an average D–D neutron rate of ${\sim} 3.2 \times 10^{16}$ s ^−1 over a period of ∼3 s, after an initial overshoot (equivalent to a D–T fusion power of ∼9.4 MW), without an uncontrolled rise in W impurity radiation, giving added confidence that impurity screening by the pedestal may also occur in ITER, as has previously been predicted (Dux et al 2017 Nucl. Mater. Energy 12 28–35).