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To determine the anti-fibrotic effects of Wnt/β-catenin signaling inhibitors on urethral stricture.Human fibroblasts were exposed to transforming growth factor beta 1 combined with various concentrations of Wnt/β-catenin inhibitors (ICG-001, IWR-1, and PRI-724), and cell proliferation and migration were evaluated. Urethral fibrosis was induced in male Sprague-Dawley rats by urethral injection of transforming growth factor beta 1 and co-treatement with inhibitors. Urethral tissues were harvested 2 weeks after the injection. The messenger ribonucleic acid and protein expression was examined for fibrosis markers Axin-1, collagen type 1, alpha smooth muscle actin, and β-catenin. Histological analysis of fibrosis and collagen deposition was also performed.Cell migration was ameliorated by ICG-001 and PRI-724. Protein and messenger ribonucleic acid expression of collagen type 1 and alpha smooth muscle actin in transforming growth factor beta 1-treated fibroblasts decreased in a concentration-dependent manner with the ICG-001 and PRI-724 treatments (P 0.05). However, there were no significant changes with the IWR-1 treatment. Collagen type I and alpha smooth muscle actin messenger ribonucleic acid and protein expression were both significantly increased in the urethral tissues of rats with transforming growth factor beta 1-induced urethral fibrosis. Rats co-treated with ICG-001 or PRI-724 showed relatively mild fibrosis and significantly reduced collagen type I and alpha smooth muscle actin messenger ribonucleic acid and protein expression (P 0.05).ICG-001 and PRI-724 significantly ameliorated urethral fibrosis induced by transforming growth factor beta 1 in rats. These results suggest that ICG-001 and PRI-724 can be developed as therapeutics for treating urethral stricture.

Catastrophic incidents would necessitate the intervention of multiple specializations with plastic surgery (PS) as an indispensable area of expertise. In view of PS, prognostic assessment of trauma patients should be focused on the qualitative value rather than mortality because plastic surgeons rarely handled patients' vital signs in actual. Thus, we explored the association between the involvement of the PS department and qualitative prognoses for severe trauma patients. From November 2014 to December 2019, we enrolled total 529 trauma patients with an injury severity score (ISS) over 15 points. We set the prognostic factors that the rate of admission in intensive care unit (ICU), total or ICU duration of hospitalization, post-discharge progress and disability diagnosis which were regarded as qualitative prognoses. The analysis was performed with logistic regression analysis or regression analysis adjusted for age, sex, past medical history, cause of trauma, and frequency of operation. Among total of 529 patients, 290 patients in PS group and 239 patients in non-PS group were analyzed. In both groups, the under-65-year ages and male patients were significantly predominant. The rate of going home showed 2.082 times higher in PS group than non-PS group after adjusting for covariates, while there was no significant difference in diagnosis of disability. Meanwhile, overall prognoses were highly correlated with either higher ISS or lower Glasgow Coma Scale (GCS). In conclusion, higher severity generally affected to the severe trauma patient's prognoses, and the PS treatment only contributes to discharge disposition to home.

A genetic etiology of male infertility is identified in fewer than 25% of infertile men, while 30% of infertile men lack a clear etiology, resulting in a diagnosis of idiopathic male infertility. Advances in reproductive genetics have provided insights into the mechanisms of male infertility, and a characterization of the genetic basis of male infertility may have broad implications for understanding the causes of infertility and determining the prognosis, optimal treatment, and management of couples. In a substantial proportion of patients with azoospermia, known genetic factors contribute to male infertility. Additionally, the number of identified genetic anomalies in other etiologies of male infertility is growing through advances in whole-genome amplification and next-generation sequencing. In this review, we present an up-to-date overview of the indications for appropriate genetic tests, summarize the characteristics of chromosomal and genetic diseases, and discuss the treatment of couples with genetic infertility by microdissection-testicular sperm extraction, personalized hormone therapy, and in vitro fertilization with pre-implantation genetic testing.

Background: Children in the affected area were exposed to large amounts of volatile organic compounds (VOCs) from the Hebei Spirit oil spill accident. Objectives: We investigated the lung function loss from the exposure to VOCs in a longitudinal panel of 224 children 1, 3, and 5 years after the VOC exposure event. Methods: Atmospheric estimated concentration of total VOCs (TVOCs), benzene, toluene, ethylbenzene, and xylene for 4 days immediately after the accident were calculated for each village (n = 83) using a modeling technique. Forced expiratory volume in 1 s (FEV1) as an indicator of airway status was measured 1, 3, and 5 years after the exposure in 224 children 4~9 years of age at the exposure to the oil spill. Multiple linear regression and linear mixed models were used to evaluate the associations, with adjustment for smoking and second-hand smoke at home. Results: Among the TVOCs (geometric mean: 1319.5 mg/m3·4 d), xylene (9.4), toluene (8.5), ethylbenzene (5.2), and benzene (2.0) were dominant in the order of air concentration level. In 224 children, percent predicted FEV1 (ppFEV1), adjusted for smoking and second-hand smoke at home, was 100.7% after 1 year, 96.2% after 3 years, and 94.6% after 5 years, and the loss over the period was significant (p < 0.0001). After 1 and 3 years, TVOCs, xylene, toluene, and ethylbenzene were significantly associated with ppFEV1. After 5 years, the associations were not significant. Throughout the 5 years’ repeated measurements in the panel, TVOCs, xylene, toluene, and ethylbenzene were significantly associated with ppFEV1. Conclusions: Exposure to VOCs from the oil spill resulted in lung function loss among children, which remained significant up to 5 years after the exposure.

Thyroid carcinoma, a disease in which malignant cells form in the thyroid tissue, is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for nearly 80% of total thyroid carcinoma cases. However, the management of metastatic or recurrent therapy-refractory PTC is challenging and requires complex carcinoma therapy. In this study, we proposed a new clinical approach for the treatment of therapy-refractory PTC. We identified sarco/endoplasmic reticulum calcium ATPase (SERCA) as an essential factor for the survival of PTC cells refractory to the treatment with paclitaxel or sorafenib. We validated its use as a potential target for developing drugs against resistant PTC, by using patient-derived paclitaxel- or sorafenib-resistant PTC cells. We further discovered novel SERCA inhibitors, candidates 7 and 13, using the evolutionary chemical binding similarity method. These novel SERCA inhibitors determined a substantial reduction of tumors in a patient-derived xenograft tumor model developed using paclitaxel- or sorafenib-resistant PTC cells. These results could provide a basis for clinically meaningful progress in the treatment of refractory PTC by identifying a novel therapeutic strategy: using a combination therapy between sorafenib or paclitaxel and specific SERCA inhibitors for effectively and selectively targeting extremely malignant cells such as antineoplastic-resistant and carcinoma stem-like cells.

Drug resistance causes therapeutic failure in refractory cancer. Cancer drug resistance stems from various factors, such as patient heterogeneity and genetic alterations in somatic cancer cells, including those from identical tissues. Generally, resistance is intrinsic for cancers; however, cancer resistance becomes common owing to an increased drug treatment. Unfortunately, overcoming this issue is not yet possible. The present study aimed to evaluate a clinical approach using candidate compounds 19 and 23, which are sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) inhibitors, discovered using the evolutionary chemical binding similarity method. mRNA sequencing indicated SERCA as the dominant marker of patient-derived anti-cancer drug-resistant hepatocellular carcinoma (HCC), but not of patient-derived anti-cancer drug-sensitive HCC. Candidate compounds 19 and 23 led to significant tumor shrinkage in a tumor xenograft model of anti-cancer drug-resistant patient-derived HCC cells. Our results might be clinically significant for the development of novel combinatorial strategies that selectively and efficiently target highly malignant cells such as drug-resistant and cancer stem-like cells.

The association between particulate matter and children's increased blood pressure is inconsistent, and few studies have evaluated indoor exposure, accounting for time-activity. The present study aimed to examine the association between personal short-term exposure to PM

Three industrial waste incinerators (IWIs) were built in 1999, 2001, and 2010, within a 3 km radius of a town with a population of around 5000 in Korea. This study evaluated whether residents near these three IWIs had increased cancer incidence than those from other areas in Korea using regional health data.Standardized incidence ratios (SIR) were calculated using the frequency of cancer cases in the National Cancer Registry of the exposed area (Buki-myeon), Chungcheongbuk-do (Chungbuk, state including Buki-myeon), and whole Korea from 1999 to 2017. A retrospective cohort was created using National Health Insurance System data from 2002 to 2018. The exposed group was defined as those having a residential history in the exposed area. The control group was defined as those having a residential history in nearby towns or counties in Chungbuk, excluding counties having living and cultural areas in other provinces and cities. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard model adjusted for age, level of health insurance fee, and smoking history.In the ecological study using National Cancer Registry data, the risk of all cancers, all cancers excluding thyroid, esophageal, stomach, and lung cancers in the exposed area were 1.13 (95% CI 1.03-1.24), 1.15 (95% CI 1.04-1.26), 1.91 (95% CI 1.13-2.89), 1.39 (95% CI 1.14-1.66), and 1.29 (95% CI 1.03-1.57) times higher than in whole Korea among exposed males, respectively. In the retrospective cohort, 4300 males (26,821 person-years) and 3796 females (24,746 person-years) in exposed group, 150,964 males (1,212,010 person-years) and 134,535 females (1,104,025 person-years) in control group were analyzed. After adjusting for several confounding factors, the risks for gallbladder cancer among males and kidney cancer among females were 2.65 (95% CI 1.38-5.06) and 2.82 (95% CI 1.13-7.03) times higher in the exposed group versus the control group, respectively.Cancer risk was higher in Koreans having residential history living near IWIs compared to the other areas. Further study warrants nationwide effects and longer follow-up of WIs for cancers in Korea.

Background: Although the evidence for the effect of short-term mortality is very high, epidemiologic studies on the effect of prolonged continuous exposure to high concentrations are rare. This study aimed to investigate how the size of the mortality effect of PM2.5 would be modified when a high concentration period persisted.Methods: We used daily mortality counts (ICD-10, non-traumatic all-cause: A00-R99, respiratory: J00-J98, and cardiovascular: I00-I99), simulated levels of daily PM2.5, measured daily mean temperature, and relative humidity data in seven metropolitan cities from 2006 to 2019. Generalized additive models (GAMs) with quasi-Poisson distribution in seven cities and random-effects meta-analyses to pool city-specific effects were used to examine the short-term effects of PM2.5. To investigate effect modification by continuous exposure to prolonged high concentrations, we applied categorical consecutive day variables to the GAMs as effect modification terms of PM2.5. Subgroup analyses were performed to examine the variation in effect modification according to the age group.Results: The mortality risk according to increase of 10 μg/m3 of PM2.5 concentration was increased by 0.30% (95%CI, 0.13–0.49), 0.48% (95%CI, -0.09–1.05), and 0.23% (95%CI, -0.10–0.57) based on the model with 0-1 lag day, for all-cause, respiratory, and cardiovascular diseases, respectively. The risk for all-cause mortality per 10 μg/m3 increase of PM2.5 in the first and fourth consecutive days were significantly increased by 0.61% (95%CI, 0.17–1.06) and 0.34% (95%CI, 0.03–0.65). The effect modification was prominent in the ³65 years old group.Conclusions: We found a significantly increased risk of all-cause, respiratory, and cardiovascular mortality for daily PM2.5 exposure when the day of high concentration began and the days lasted for more than 4 days with high concentration of ≥35 μg/m3. The elderly showed a stronger effect of persistently high PM2.5.