Abstract. Ischemia-induced oxidative damage to the reperfused kidney was examined. A modified chemiluminescence method, an in situ nitro blue tetrazolium perfusion technique, and a DNA fragmentation/apoptosis-related protein assay were adapted for demonstration de novo and co-localization of reactive oxygen species (ROS) production and apoptosis formation in rat kidneys subjected to ischemia/reperfusion injury. The results showed that prolonged ischemia potentiated proapoptotic mechanisms, including increases in the Bax/Bcl-2 ratio, CPP32 expression, and poly-(ADP-ribose)-polymerase fragments, and subsequently resulted in severe apoptosis, including increases in DNA fragmentation and apoptotic cell number in renal proximal tubules (PT) and distal tubules (DT) in a time-dependent manner. The increased level of ROS detected on the renal surface was correlated with that in blood and was intensified by a prolonged interval of ischemia. The main source of ROS synthesis was the PT epithelial cells. The ROS and apoptotic nuclei detected in the PT cells can be ameliorated by superoxide dismutase (SOD) treatment before reperfusion. However, the apoptotic nuclei remained in DT in the SOD-treated rats, indicating that formation of apoptosis in DT was not influenced by the small amounts of ROS produced. In PT and DT cell cultures, significant increases in apoptotic cells and ROS were evident in PT cells after hypoxia/reoxygenation insult. Furthermore, the oxidative damage in PT, but not in DT, can be alleviated by ROS scavengers SOD and hexa(sulfobutyl)fullerene, confirming that PT are vulnerable to ROS. These results lead us to conclude that ROS produced in significant amounts in PT epithelium under ischemia/reperfusion or hypoxia/reoxygenation conditions may be responsible for the apoptotic death of these cells.
The core principle of HyFlex ('hybrid' and 'flexible') learning is to maintain learning equity under most circumstances. Within a blended framework in precision medical education, how different preferences of synchronous learning environment influence learning process and outcome is limited. We investigated students' preclass online video learning experiences and their choices toward synchronous class formats.This was a mixed-methods study. During the 2021 academic year, all 5th-year medical students who had viewed online video clips presenting core concepts were asked to complete a survey on their preference for future synchronous class format (face-to-face, online, or HyFlex) and asked to provide reflective comments on their self-learning. Anonymous survey data, online records, and summative assessment scores (short-term learning outcomes) were collected. Kruskal - Wallis or Chi-square tests were used to compare differences between groups, and multiple linear regression was managed to select the factors associated with various choices. The students' comments were coded in a descriptive thematic analysis.Among 152 medical students, 150 responded to the questionnaires, and 109 provided comments. Medical students spent a median of 32 min online, significantly shorter in the face-to-face group than in the online and HyFlex groups. The online group had a lower preclass video completion rate for certain concepts. The choice was not associated with short-term learning outcomes. Student feedback revealed a higher frequency of multiple themes for each student in the face-to-face and HyFlex groups, and these themes fell into the categories of learning efficiency, focus concentration, and course attractiveness.Linking the choice of the class format and learning experiences of preclass online videos sheds light on a step further within a blended framework of precision medical education. Supplement of online interactive elements may help secure learning engagement among students choosing 'online only' class format of HyFlex learning.
Liver transplantation (LT) is the definite curative treatment for hepatocellular carcinoma (HCC), but recurrence can occur even under stringent criteria. "Delayed" HCC recurrence (>3 years after LT) is not common. Here, we present the clinical features of patients who developed delayed HCC recurrence after LT.
Objective To evaluate the association of clinicopathologic factors and prognostic value with the expression of cyclooxygenase 1 and 2 in patients with gastric adenocarcinoma. Summary Background Data Epidemiologic studies have indicated that nonsteroidal antiinflammatory drugs reduce the risk of colon cancer by as much as 40% and also decrease the risk of gastric cancer. Recently, gastric cancer was found to express constitutive cyclooxygenase 1 and inducible cyclooxygenase 2 isoenzymes. Nonsteroidal antiinflammatories, which may function as cyclooxygenase inhibitors, inhibited the growth of gastric cancer cells. These two isoenzymes’ expressions associated with traditional clinicopathologic factors have not been fully evaluated, and their prognostic value for determining survival in patients remains to be clarified. Methods Seventy-one specimens resected from patients with gastric adenocarcinoma were investigated by immunohistochemical stain against cyclooxygenase 1 and 2. The 71 specimens were divided into stain-positive and stain-negative groups. Correlations between cyclooxygenase 1 and 2 expression, various clinicopathologic factors *including vascular invasion and Helicobacterpylori infection), and prognosis were studied. Results The cyclooxygenase 2-positive group was significantly correlated with vascular invasion and H.pylori infection by univariate and multivariate analysis. In patients with cyclooxygenase 2-positive cancer, the prognosis was significantly poorer than in those with cyclooxygenase 2-negative cancer. However, multivariate analysis showed that vascular invasion, serosal invasion, and lymph node metastasis were independent prognostic factors for patients with gastric cancer, but cyclooxygenase 2 expression was not. There was no significant correlation between cyclooxygenase 1 expression and clinicopathologic factors and prognosis. Conclusions Upregulated cyclooxygenase 2 expression was associated with H. pylori infection in gastric cancer and was also strongly correlated with positive vascular invasion, which was an independent prognostic factor for poorer survival in this study. The usefulness of cyclooxygenase 2 inhibitors in the prevention or treatment of gastric cancer remains undetermined but deserves further investigation.
We discuss several problems on the structure of nil rings from the linear algebra point of view. Among others, a number of questions and results are presented concerning algebras of infinite matrices over nil algebras, and nil algebras of infinite matrices over fields, which are related to the famous Koethe's problem. Some questions on radicals of tensor products of algebras related to Koethe's problem are also discussed.
Many traditional pharmacopeias include Aristolochia and related plants, which contain nephrotoxins and mutagens in the form of aristolochic acids and similar compounds (collectively, AA). AA is implicated in multiple cancer types, sometimes with very high mutational burdens, especially in upper tract urothelial cancers (UTUCs). AA-associated kidney failure and UTUCs are prevalent in Taiwan, but AA's role in hepatocellular carcinomas (HCCs) there remains unexplored. Therefore, we sequenced the whole exomes of 98 HCCs from two hospitals in Taiwan and found that 78% showed the distinctive mutational signature of AA exposure, accounting for most of the nonsilent mutations in known cancer driver genes. We then searched for the AA signature in 1400 HCCs from diverse geographic regions. Consistent with exposure through known herbal medicines, 47% of Chinese HCCs showed the signature, albeit with lower mutation loads than in Taiwan. In addition, 29% of HCCs from Southeast Asia showed the signature. The AA signature was also detected in 13 and 2.7% of HCCs from Korea and Japan as well as in 4.8 and 1.7% of HCCs from North America and Europe, respectively, excluding one U.S. hospital where 22% of 87 "Asian" HCCs had the signature. Thus, AA exposure is geographically widespread. Asia, especially Taiwan, appears to be much more extensively affected, which is consistent with other evidence of patterns of AA exposure. We propose that additional measures aimed at primary prevention through avoidance of AA exposure and investigation of possible approaches to secondary prevention are warranted.
Liver fatty change (steatosis), the accumulation of fat within liver cells, is a common histological finding in liver biopsies. The histological changes of steatosis, such as the distribution of fatty droplets, cannot be resolved by conventional ultrasound. High frequency ultrasound (/spl ges/20 MHz), on the other hand, has the potential to reveal more detail of steatosis. B-mode HF ultrasound images of 19 fresh human liver samples were obtained to evaluate ultrasound's ability to determine the steatosis grade. The images were acquired by a mechanically controlled 25 MHz single crystal probe. Image features derived from gray level concurrence and non-separable wavelet transform were extracted to classify steatosis grade using a support vector machine classifier. Each liver sample subsequently underwent histological examination and liver steatosis was graded and classified according to the number of hepatocytes affected. It is found that, compared with the results acquired from conventional ultrasound at 7 MHz, classification accuracy is clearly better at 25 MHz. Thus, liver steatosis can be more accurately characterized using high frequency B-mode ultrasound. Limitations and potential solutions of liver steatosis using high frequency ultrasound are also discussed.
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