Direct Activation of Bmi1 by Twist1: Implications in Cancer Stemness, Epithelial-Mesenchymal Transition, and Clinical Significance
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Kou-Juey Wu
Cancer stemness is a concept used to describe a minor population of cells (cancer stem cells-CSCs) residing in a tumor, which possess self-renewal properties and are resistant to chemo/radiation therapy. Epithelial-mesenchymal transition (EMT), a major mechanism of cancer metastasis, is a process which generates cells with stem-like properties. The relationship between cancer stemness and EMT is well documented but without detailed mechanistic explanation. Bmi1 belongs to the polycomb repressive complex 1 (PRC1) which maintains self-renewal and stemness. Recent results showed that Twist1, an EMT regulator, directly activates Bmi1 and these two molecules function together to mediate cancer stemness and EMT. These results provide a molecular explanation of the relationship between cancer stemness and EMT. Bmi1 is frequently overexpressed in various types of human cancers and can confer drug resistance. Twist1 is also overexpressed in various human cancers with prognostic significance. The functional interdependence between Twist1 and Bmi1 provides a fresh insight into the molecular mechanism of EMT-induced cancer stemness. Further investigation of the mechanisms mediating EMT and cancer stemness will be helpful in the management and treatment of metastatic cancers.
Arthroscopy- Assisted Surgery for Tibial Plateau Fractures
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Yi-Sheng Chan
Like other intra-articular fractures, the tibial plateau fracture is challenging for orthopedic surgeons because of its severity of trauma, associated soft tissue injuries. Open reduction incurs serious complications, especially wound healing after traditional dissections. Unsatisfactory results often occur in complex or bicondylar tibial plateau fractures. Traditional surgical methods achieved satisfactory results in 70– 80% of cases. However, these methods have a high incidence of complications including loss of reduction, infection, and septic arthritis. The advantages of arthroscopy-assisted reduction and internal fixation include direct visualization of intra-articular fracture, accurate fracture reduction, and reduced morbidity. It is straightforward in the diagnosis and treatment of meniscal and ligamentous injuries, and removal of loose fragments. Good early to medium-term results of arthroscopically assisted osteosynthesis of tibial plateau fractures have been reported. The author reviews the current surgical principles, pitfalls, approaches, clinical results, and complications of arthroscopyassisted surgery for tibial plateau fractures.
Background: Individuals with non-alcohol fatty liver disease (NAFLD) exhibit impaired liver regeneration in a clinical setting and animal experiments. Adiponectin signaling is recognized as an important pathway of lipid metabolism, energy expenditure, anti-inflammation, and cellular proliferation. We herein investigate hepatic adiponectin signaling in dietary steatotic murine models undergoing hepatectomy, which has never been explored.
Methods: Sprague-Dawley rats fed with a normal diet (normal), high fat diet (HF), and a methionine-choline deficiency diet for 1 week (MCD 1W) and 5 weeks (MCD 5W), were used. The animals underwent 70% hepatectomy and were thereafter sacrificed at indicated time points.
Results: MCD 5W and HF displayed decreased Ki-67 labeling index and restituted liver mass compared to normal. Hepatic adiponectin, as well as TNF-α, of MCD5W and HF were increased compared to normal; whereas adiponectin receptor type 1 (AdipoR1) and adiponectin receptor type 2 (AdpoR2) were reciprocally decreased when compared to normal. PPARα, a downstream molecule of AdipoR2 axis, was decreased in MCD 5W compared to normal. Adenosine monophosphate- activated protein kinase (AMPK), a downstream molecule of AdipoR1 axis, was inactivated soon after hepatectomy in normal; whereas activation of AMPK persisted until day 3 after hepatectomy in MCD 5W and HF.
Conclusions: Reciprocal expression of adiponectin and its receptors in steatotic rats represents a unique form of adiponectin signaling disruption, which might be associated with impaired liver regeneration.
Background: In chronic hepatitis B, the HBcAg viral protein in liver tissue demonstrates a positive correlation with serum aminotransferase levels, serum hepatitis B viral DNA, and histological activities. Little is known if similar relationships exist for chronic hepatitis C. This study attempted to determine if expression of the hepatocyte NS3 protein of the hepatitis C virus (HCV-NS3) was correlated with the serum HCV-RNA load, hepatitis activity, or other clinical parameters.
Methods: Clinical and histological data of 214 patients with chronic hepatitis C were retrospectively reviewed. A mouse monoclonal antibody was used to detect HCV-NS3 in hepatocytes. The staining intensity was scored semiquantitatively as 0~3+, and its correlations with the serum HCV-RNA load, hepatitis activity, and other clinical parameters were analyzed.
Results: In total, 202 (94%) of the 214 liver biopsies were positive for HCV-NS3, and the intensity of HCV-NS3 staining was 0 in 12 (6%), 1+ in 181 (84%), and 2+ in 21 patients (10%). The intensity of HCV-NS3 expression in the samples did not correlate with patient age (p = 0.302, ANOVA), patient gender (p = 0.130, Fisher's exact test), the alanine transaminase level (p = 0.177, ANOVA), serum HCV-RNA level (p = 0.305, ANOVA), HCV antibody titer (p = 0.139, Chi-squared test), hepatitis activity index score (p = 0.861, Chisquared test), or sustained viral response rate (p = 0.861, Chi-squared test).
Conclusions: This HCV-NS3 immunohistochemical staining method was reliable for detecting HCV in liver specimens. Hepatocyte expression of HCV-NS3 was not correlated with the serum viral load, severity of hepatic injury, or treatment response.
The Diagnostic Value of Computed Tomographic Coronary Angiography in Patients with Acute Myocardial Infarction versus Stable Angina Pectoris: A Preliminary Report
Background: Computed tomographic coronary angiography (CTA) is a non-invasive alternative to conventional coronary angiography (CCA) in detecting chronic coronary artery disease (CAD). However, the value of CTA in estimating acute myocardial infarction (AMI) has not been evaluated.
Methods: CTA and CCA were performed on 10 patients with non-ST-elevated AMI and 17 patients with stable angina pectoris. The plaque components and stenosis severity were assessed by both modalities to clarify the diagnostic values of CTA in AMI and stable angina pectoris.
Results: A high total coronary artery calcium (CAC) score was significantly correlated with the presence of CAD and the target lesion CAC score (p < 0.01). The AMI group tended to have a lower target CAC score (p = 0.10) and target plaque burden (p = 0.27), compared to the stable angina pectoris group. To estimate the coronary artery stenotic severity, CTA and CCA had concordant correlations in all segments, except in the proximal left anterior descending (LAD) artery. The calcium score and calcification fraction percentage in the proximal LAD artery were significantly higher than those of other segments (p < 0.01). Compared to CCA, CTA overestimated the severity of stenosis in the proximal LAD arterial segment in the stable angina pectoris group (p = 0.028), but not in the AMI group.
Conclusions: CTA has diagnostic values similar to those of CCA in detecting coronary lesions in patients with AMI or stable angina pectoris. However, a high level of plaque CAC in the stable angina pectoris group may lead to an overestimation of the severity of coronary stenosis, especially in the proximal LAD arterial segment. Although less remarkable, the impact of CAC on the diagnostic value of CTA was still substantial in patients with AMI.
Background: Depression and heavy stress have been reported as two important problems for medical students in previous studies; and stress and depression levels were also related to gender and grades. The aims of this article were to investigate the emotional problems of Taiwanese interns and clerks, and to clarify their relationship to work circumstances, identity of interns and clerks in the hospitals, gender discrepancy and their levels of stress and depression.
Methods: Three medical centers in Taiwan were selected in this study. All interns in the three medical centers and clerks in Chang Gung Memorial Hospital were invited to complete an anonymous self-report questionnaire. The questionnaire included demographic data, levels of various stresses in hospitals
recorded with visual analog scales, and a Chinese version of Zung's Selfadministered Depression Scale. One-way analysis of variance was also adopted to compare the distress scores, and the Scheffe test was chosen for the post hoc comparisons.
Results: First, working in different medical centers was not a factor influencing levels of stress and depression of interns. Second, interns had higher stress levels of "work loading" and "occupational risks", and more depressive symptoms, such as "poor sleep quality", "poor appetite", "libido loss", "body weight loss", and "anhedonia". However, identity did not significantly impact levels of depression. Third, gender discrepancy showed significant influences on some stress sources and depressed symptoms.
Conclusions: When comparing some depressive symptoms and stress sources among medical students, differences of gender and identities were statistically significant. Further longitudinal studies are needed.
Comparison between 0.08% Ropivacaine and 0.06% Levobupivacaine for Epidural Analgesia during Nulliparous Labor: A Retrospective Study in A Single Center
Background: Levobupivacaine and ropivacaine are new local anesthetics that have effects similar to bupivacaine. However, the relative potency of these two drugs is controversial. The purpose of this retrospective study was to assess whether a combination of 0.06% levobupivacaine and 0.0002% fentanyl had the same effects as 0.08% ropivacaine and 0.0002% fentanyl on the mode of delivery and other obstetric outcomes when used for epidural analgesia of labor in nulliparous women.
Methods: Computer records of 392 Asian nulliparous parturients, who had presented with spontaneous labor or spontaneous rupture of the membranes, and had received epidural analgesia were retrospectively reviewed. Of these, 193 received 0.08% ropivacaine and 199 received 0.06% levobupivacaine. Fentanyl (0.0002%) was used in both regimens.
Results: There were no significant differences in the mode of delivery, duration of labor, or neonatal outcome between the two groups. In the levobupivacaine group, the parturients required top-up boluses of local anesthetics more frequently (1.4 ± 1.6 vs. 0.9 ± 1.3, p < 0.0001), and the incidence of temporary maternal fever (25% vs. 15%, p = 0.024) and the cost of local anesthetic were higher (292 ± 183 NTD vs. 146 ± 104 NTD, p < 0.0001). However, the amount of local anesthetic administered during labor was lower (79 ± 49 mg vs. 114 ± 81 mg, p < 0.0001) than for the ropivacaine group.
Conclusions: 0.06% levobupivacaine was as effective as 0.08% ropivacaine, when both were used with 0.0002% fentanyl for labor epidural analgesia of nulliparous women.
An Anatomical Study of the Inferior Oblique Muscle with Emphasis on Its Nerve Entry
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Vishal Kumar, BV Murlimanju, P Devika, Narga Nair, Shakuntala R Pai, Thejodhar Pulakunta, NS Naveen
Background: Anatomical studies regarding the inferior oblique muscle are scarce and the exact location of the entry of oculomotor nerve to the muscle has not been reported. In the present study, the objectives were to examine the exact location of the entry of oculomotor nerve to the inferior oblique muscle and to study the topographical anatomy of the muscle.
Methods: The study included 56 intact orbits from 28 embalmed south Indian adult cadavers. The entire course of the nerve to the inferior oblique was exposed from both anterior and posterior aspects in all specimens. The exact location of the entry of nerve supplying the inferior oblique muscle was identified and the distances of the muscle from inferior and medial orbital margins were measured.
Results: The oculomotor nerve entered the inferior oblique muscle through the orbital surface in 42 (75%) cases, through the ocular surface in 10 (17.9%) cases and through the posterior border in 4 (7.1%) cases. The distance of the muscle from the inferior orbital margin was 1 mm in majority (78.5%) of the cases. The distance of the muscle from the medial orbital margin was 11 mm in majority (42.8%) of the cases.
Conclusion: The present study reports that the oculomotor nerve most often enters the inferior oblique muscle through its orbital surface. Detailed knowledge of the topographical anatomy of inferior oblique muscle and its site of nerve entry are essential for surgeons when performing ophthalmological surgery and regional anesthesia.
Background : The meniscus plays a key role in the functioning of the knee. At the present time, meniscal repair has becomes the main treatment for meniscal tear. Compared to open surgery, arthroscopic meniscal repair has become popular because of shorter time need for the operation, the smaller wound, and better accessibility to the tear portion, which is particularly difficult during open surgery. Three arthroscopic techniques are widely used, namely inside-out, outside-in, and all-inside. Arthroscopy all inside meniscal repair has the lowest neurovascular injury rate.
Methods : This study prospectively evaluated 31 consecutively treated patients to determine the effectiveness/safety of arthroscopic meniscal repair using the FasTFix repair system. The inclusion criteria for this study were: vertical fullthickness tear > 10 mm in length; location of the meniscal tear < 6 mm from the meniscocapsular junction; repair of the meniscus solely with the FasTFix system; no former meniscus surgery; and no evidence of arthritis during arthroscopy. Anterior cruciate ligament (ACL) deficient knees were reconstructed using a hamstring autograft at the time of the meniscal repair. Follow-up examinations consisted of Lysholm knee score, Tegner activity score and radiographic evaluation.
Results : After an average of 3 years follow-up, no symptoms of meniscal tears were found in 30/31 of the cases. For patients with isolated meniscal repair or concurrent ACL reconstruction, the Lysholm and Tegner activity scores had significantly improved postoperatively. No neurovascular or other major complications were directly associated with the use of the device.
Conclusions : Arthroscopic all-inside repair using the FasT-Fix device appears to be a safe and effective procedure.