Comparing the imaging characteristics of middle-aged patients with multiple sclerosis and CADASIL: A retrospective cross-sectional study.

BACKGROUND: Few studies have quantitatively analyzed the imaging disparities between multiple sclerosis (MS) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to compare the imaging characteristics of MS and CADASIL in middle-aged patients. MATERIALS AND METHODS: This retrospective study used a single-center database and included patients aged 40-60 years with MS and CADASIL who underwent the designated imaging protocol including 3D T1-weighted imaging and fluid attenuated inversion recovery (FLAIR), diffusion tensor imaging and susceptibility-weighted imaging between January 2018 and March 2023. Patients with MRI-detected macrobleeds were excluded. RESULTS: A total of 27 patients with MS (mean age, 46.7 years ± 4.4, 8 men) and 30 patients with CADASIL (mean age, 51.6 years ± 5.8, 14 men) were included. No significant differences were observed in the Fazekas grades of white matter lesions (WMLs). Patients with CADASIL exhibited greater external capsule involvement (56.7% vs.18.5 %; p = 0.006), whereas the MS group had more lesions in the corpus callosum (81.5% vs. 53.3 %, p = 0.02) and brainstem (74.1% vs. 46.7 %, p = 0.04). The CADASIL group exhibited a higher incidence of microbleeds (12.07 vs. 0.11, p = 0.001). The WMLs in the MS group exhibited a lower T1 lesion/cerebrospinal fluid signal index (2.206 vs. 2.882, p < 0.001). A value of ≤2.57 demonstrated a sensitivity of 92.6 % and a specificity of 90.0 % in differentiating MS. Patients with MS had a thinner corpus callosum (7.18 mm vs 7.86 mm, p = 0.04), while patients with CADASIL showed significantly higher mean diffusivity (0.8776 × 10-3 vs. 0.7637 × 10-3 mm2/s, p = 0.03) and lower fractional anisotropy (0.7581 vs. 0.8389, p = 0.04) in the splenium of the corpus callosum. CONCLUSION: Middle-aged patients with MS and CADASIL showed comparable Fazekas grades for WMLs. However, lesion distribution, T1 signal characteristics, and splenic diffusivity changes can help differentiate between MS and CADASIL.

Lenvatinib Suppresses Protein Kinase B Signaling and Induces Apoptosis in Osteosarcoma Cells.

BACKGROUND/AIM: Lenvatinib, an oral multikinase inhibitor, has demonstrated promising activity in patients with osteosarcoma (OS). Therefore, it is worth exploring the inhibitory efficacy and mechanism of action of lenvatinib in osteosarcoma. The primary goal of this study was to examine the inhibitory effectiveness and mechanism of lenvatinib on the growth and invasion of OS cells. MATERIALS AND METHODS: The effects of lenvatinib on cell viability, apoptosis, protein kinase B (AKT) activation, its downstream effector proteins involved in tumor progression, and invasion capability were assessed using MTT assay, flow cytometry, western blotting, and invasion/migration assay on U-2 OS and MG63 cells. RESULTS: Lenvatinib effectively induced cytotoxicity, apoptosis, as well as extrinsic and intrinsic apoptotic signaling in OS cells. Lenvatinib also significantly decreased the invasion/migration capability, AKT activation, and downstream effector proteins. CONCLUSION: The anti-OS effect of lenvatinib may be associated with the induction of apoptosis and the inactivation of AKT.

Influence of autonomous cortisol secretion in patients with primary aldosteronism: subtype analysis and postoperative outcome.

Context: Autonomous cortisol secretion (ACS) has a relatively high prevalence in patients with primary aldosteronism (PA). There is still a lack of relevant studies to analyze the influence of ACS on diagnosing and managing PA. Objective: To evaluate the influence of ACS on image-adrenal venous sampling (AVS) correlation and the postoperative results. Methods: This was a retrospective study using the Taiwan Primary Aldosteronism Investigation database from July 2017 to April 2020, with 327 PA patients enrolled. A total of 246 patients were included in the image-AVS analysis. Patients who had undergone unilateral adrenalectomy and a 12-month follow-up were included in the postoperative analysis. Results: Sixty-five patients (26.4%) had ACS. The image-AVS discordance rate was higher in the ACS group compared to the non-ACS group (75.4% (n = 49) vs 56.4% (n = 102); odds ratio (OR) = 2.37 (CI: 1.26-4.48); P = 0.007). The complete biochemical success rate was higher in the non-ACS group than that in the ACS group (98.1% (n = 51) vs 64.3% (n = 9); OR = 28.333 (CI: 2.954-271.779); P = 0.001). In logistic regression analysis, ACS was the only factor associated with lower biochemical success (OR = 0.035 (CI: 0.004-0.339), P = 0.004). Conclusion: PA patients with ACS have higher image-AVS discordance rate and worse biochemical outcomes after surgery. ACS was the only negative predictor of postoperative biochemical outcomes. Further studies and novel biomarkers for AVS are crucial for obtaining better postoperative outcomes in PA patients with ACS.

Let-7g Upregulation Attenuated the KRAS-PI3K-Rac1-Akt Axis-Mediated Bioenergetic Functions.

The aberrant activation of signaling pathways contributes to cancer cells with metabolic reprogramming. Thus, targeting signaling modulators is considered a potential therapeutic strategy for cancer. Subcellular fractionation, coimmunoprecipitation, biochemical analysis, and gene manipulation experiments revealed that decreasing the interaction of kirsten rat sarcoma viral oncogene homolog (KRAS) with p110α in lipid rafts with the use of naringenin (NGN), a citrus flavonoid, causes lipid raft-associated phosphatidylinositol 3-kinase (PI3K)-GTP-ras-related C3 botulinum toxin substrate 1 (Rac1)-protein kinase B (Akt)-regulated metabolic dysfunction of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), leading to apoptosis in human nasopharyngeal carcinoma (NPC) cells. The use of lethal-7g (let-7g) mimic and let-7g inhibitor confirmed that elevated let-7g resulted in a decrease in KRAS expression, which attenuated the PI3K-Rac1-Akt-BCL-2/BCL-xL-modulated mitochondrial energy metabolic functions. Increased let-7g depends on the suppression of the RNA-specificity of monocyte chemoattractant protein-induced protein-1 (MCPIP1) ribonuclease since NGN specifically blocks the degradation of pre-let-7g by NPC cell-derived immunoprecipitated MCPIP1. Converging lines of evidence indicate that the inhibition of MCPIP1 by NGN leads to let-7g upregulation, suppressing oncogenic KRAS-modulated PI3K-Rac1-Akt signaling and thereby impeding the metabolic activities of aerobic glycolysis and mitochondrial OXPHOS.

The Presence of Diabetes Mellitus or Pre-diabetes Mellitus Increases Mortality from Heart Disease in a Taiwanese Population: A 10-year Follow-Up Study.

BACKGROUND: We evaluated hyperglycemia-associated mortality in the Taiwanese population by conducting a 10-year retrospective cohort study. METHODS: From 2007 to 2017, all participants, regardless of their age or underlying diseases, were identified at a Health Screening Center in Taiwan. Overall, 114,534 participants were included in the analysis. They were classified into three subgroups according to glycemia and smoking status by combining survival for data analysis. RESULTS: The mean follow-up time, age, and body mass index (BMI) were 8.14 ± 2.22 years, 40.95 ± 12.14 years, and 23.24 ± 3.65 kg/m2, respectively. The cumulative death rate increased from 0.9% in the normal fasting blood glucose(FBG) subgroup to approximately 6% in the diabetes FBG subgroup. After adjusting for age, gender, BMI, high-density lipoprotein, triglycerides, waist circumference(WC), and smoking status, the hazard ratio (HR) for all-cause, cancer, and heart disease mortality in the diabetes mellitus(DM) subgroup was 1.560, 1.381, and 1.828, respectively.HR was 0.989 in all-cause, 0.940 in cancer, and 1.326 in heart disease in the pre-DM subgroup. CONCLUSION: Being tested for pre-DM is related to a higher risk of death from heart disease in the Taiwanese population at baseline. Therefore, cardiovascular risk must be actively measured among diabetes patients every visit.

Clinical characteristics and prognosis of optic neuritis in Taiwan - a hospital-based cohort study.

BACKGROUND: Optic neuritis (ON) is an inflammatory disease of optic nerve. The distinct etiologies of ON significantly influence its clinical manifestation, neuroimaging findings, and visual outcomes. However, the clinical characteristics might be influenced by the racial differences. The purpose of this study is to investigate the clinical characteristics of various types of ON at a Taiwanese tertiary center. METHODS: This cohort study analyzed 163 patients who received treatment and continued following-up for ON between 2015 and 2022. We selected patients who had been tested for anti-aquaporin-4 antibody (AQP4-Ab) and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab). The participants were classified into four groups on the basis of their etiologies, specifically (1) multiple sclerosis (MS)-related, (2) AQP4-Ab-positive, (3) MOG-Ab-positive, or (4) idiopathic ON. The researchers recorded the patients' clinical characteristics, treatment course, magnetic resonance imaging and optical coherence tomography (OCT) findings, and visual outcomes. RESULTS: MOG-Ab-positive group had higher percentages of disk swelling and pain with eye movement. Long optic nerve and perineural enhancement are the hallmarks of MOG-Ab-related ON. The ON relapse rate was higher in AQP4-Ab-positive group. Although members of AQP4-Ab-positive group received immediate steroid pulse therapy, these patients experienced the worst visual outcomes. Moreover, a thinner retinal nerve fiber layer (RNFL) was noted in AQP4-Ab-positive group. MS group had a higher incidence of extra-optic nerve lesions. Multivariate regression identified pretreatment visual acuity and RNFL thickness as the important factors affecting visual outcomes. CONCLUSIONS: This cohort study identified the clinical features of different types of ON. Patients with AQP4-Ab-positive ON had poorer visual outcomes, which may be attributed to multiple relapses and profound nerve damage, as revealed by OCT findings. Patients with MOG-Ab-positive ON displayed long optic nerve enhancement but had more favorable prognoses. Thus, antibody-based classification facilitates treatment and prognosis in ON.

Verifying the accuracy of self-reported smoking behavior in female volunteer soldiers.

Smoking rates in the military are evaluated through questionnaire surveying. Because the accurate identification of smokers facilitates the provision of smoking cessation services, this study conducted urine cotinine concentration testing to verify the accuracy of self-reported smoking behavior by female volunteer soldiers and analyzed the effects of second-hand smoking on urine cotinine concentrations. This study is a cross-sectional study conducted using purposive sampling on female volunteer soldiers receiving training at the Taichung Recruit Training Center in May 2014. This study simultaneously collected questionnaires and urine samples, and urine samples were analyzed with an enzyme-linked immunosorbent assay. The self-reported smoking rate of female volunteer soldiers was 19.3%, whereas the smoking rate as determined by urine cotinine concentration testing was 26.3%, indicating an overall underestimation of 7.0%. Chi-square (χ2) goodness of fit test results indicated that the distribution of self-reported smoking behaviors and that verified from urine cotinine concentration testing were significantly different. The sensitivity of self-reported smoking behavior was 66.7% with a specificity of 97.6%. There was no significant association between second-hand smoking and urine cotinine concentrations. Questionnaire survey self-reporting methods could underestimate the smoking behavior of female volunteer soldiers and routine testing with biochemical verification is necessary.

Anti-Oxidative Effect of Pu-erh Tea in Animals Trails: A Systematic Review and Meta-Analysis.

This study adopted systematic literature review and meta-analysis methodology to explored anti-oxidative effect of pu-erh tea. Study authors have systemically searched seven databases up until 21 February 2020. In performing the literature search on the above-mentioned databases, the authors used keywords of pu-erh AND (superoxide dismutase OR glutathione peroxidase OR malondialdehyde). Results derived from meta-analyses showed statistically significant effects of pu-erh tea on reducing serum MDA levels (SMD, −4.19; 95% CI, −5.22 to −3.15; p < 0.001; I2 = 93.67%); increasing serum SOD levels (SMD, 2.41; 95% CI, 1.61 to 3.20; p < 0.001; I2 = 91.36%); and increasing serum GSH-Px levels (SMD, 4.23; 95% CI, 3.10 to 5.36; p < 0.001; I2 = 93.69%). Results from systematic review and meta-analyses validated that various ingredients found in pu-erh tea extracts had anti-oxidation effects, a long-held conventional wisdom with limited supporting evidence.

The Association between Serum Testosterone and Hyperuricemia in Males.

Gout is a common systemic inflammatory disease with a male predominance. This study aimed to determine the relationship between serum total testosterone level and hyperuricemia. Data on 1899 men, collected from 2007 to 2017, were included in the analysis. Serum testosterone and urate (SU) were measured on enrolment. The primary endpoints were SU levels ≥ 7 mg/dL and ≥9 mg/dL. On enrolment, participants had a mean age of 45.6 years and mean total testosterone and SU levels of 510 ng/dL and 6.6 mg/dL, respectively. The mean total testosterone levels were 533 and 470 ng/dL in patients with SU levels < 7 mg/dL and ≥7 mg/dL, respectively (p < 0.001); and 515 and 425 ng/dL in patients with SU levels < 9 mg/dL and ≥9 mg/dL, respectively (p < 0.001). After adjusting for age, body mass index, creatinine, serum lipid, fasting blood glucose, systolic blood pressure, and diastolic blood pressure, low testosterone level (<400 ng/dL) was significantly associated with an SU level ≥ 7 mg/dL (hazard ratio: 1.182, 95% confidence interval: 1.005−1.39) and ≥9 mg/dL (hazard ratio: 1.905, 95% confidence interval: 1.239−2.928). In men, a low testosterone level may be associated with an increased risk of hyperuricemia.

Overexpression of Cell-Surface Marker SLC16A1 Shortened Survival in Human High-Grade Gliomas.

Solute carrier family 16 member 1 (SLC16A1) is a crucial transcription factor in modifying cancer progression and metastasis. However, its character in defining the clinical prognosis of human gliomas has not been illuminated. In our analysis from PREdiction of Clinical Outcomes from Genomic Profiles (PRECOG), The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA), we found that SLC16A1 mRNA expression level was significantly increased in high-grade gliomas in contrast to low-grade gliomas and non-tumor controls (P < 0.05). Kaplan-Meier analysis of four independent cohort studies from the Gene Expression Omnibus (GEO) profile, TCGA, and CGGA which consistently presented patients with high SLC16A1 mRNA expression displayed poor overall survival in high-grade glioma patients (P < 0.05 by log-rank test). Based on the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), the protein-protein interaction analysis of SLC16A1-regulated oncogenesis showed SLC16A1 as a potential hub protein. Immunohistochemical staining exhibited that SLC16A1 protein overexpressed in high-grade gliomas compared with low-grade clinical glioma samples. All these findings suggest that SLC16A1 expression has a positive correlation with WHO pathological grading and poor survival. SLC16A1 might be a potential biomarker of prognosis in human gliomas.

Common mental disorders in Taiwanese consumers of commercial low-dose computed tomography lung cancer screening: Comparison with a nationally representative sample.

BACKGROUND/PURPOSE: We examined the prevalence of probable common mental disorders (CMDs) in commercial low-dose computed tomography (LDCT) lung cancer screening consumers relative to the general population and to determine the correlates of probable CMDs among screening participants. METHODS: Commercial LDCT lung cancer screening consumers (N = 1323) were compared with a nationally representative sample from the Taiwan Social Change Survey (TSCS) (N = 2034). Respondents scoring ≥3 on the Chinese Health Questionnaire were classified as having a probable CMD. Logistic regression was used to investigate differences between the two groups and correlates of probable CMDs among LDCT lung cancer screening participants. RESULTS: The prevalence of probable CMDs was higher among LDCT lung cancer screening participants (25.47%) than among TSCS adults (21.56%). Compared with the TSCS sample, the screening participants had a higher probability of CMDs (OR = 1.40, 95% CI = 1.13-1.73), higher education levels (OR = 7.95, 95% CI = 6.00-10.53), and a history of drinking (OR = 11.85, 95% CI = 9.45-14.85) or betel-quid use (OR = 5.43, 95% CI = 3.98-7.42) but were less likely to smoke (OR = 0.52, 95% CI = 0.40-0.68). Among the screening participants, being female (OR = 1.37, 95% CI = 1.02-1.84) and a current smoker (OR = 1.74, 1.19-2.54) and living near ≥2 smoking family members (OR = 2.30, 95% CI 1.57-3.38) were associated with an increased likelihood of having CMDs. CONCLUSION: Commercial LDCT lung cancer screening users may have a positive association with probable CMDs compared to the general population. Screening programs should consider including criteria and providing psychoeducation to improve the physical and mental outcomes of participants. CLINICAL TRIAL REGISTRATION: Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) do not require registration.

Inhibitory effects of pu-erh tea on alpha glucosidase and alpha amylase: a systemic review.

OBJECTIVE: Pu-erh tea was presumed to have anti-hyperglycemic effects via inhibition on alpha-amylase and alpha-glucosidase. However, no integerated literatures were published to substantiate such presumption. METHODS: Current study adopted systemic review method to validate inhibitory effects on alpha amylase and alpha-glucosidase. Five English databases (PubMed, EBSCO, SCOPUS, Cochrane Library, Web of Science) and three Chinese ones (Airti Library, CNKI Library, and Google Scholar) were searched up to 22 March 2018 for eligible literatures, using keywords of Pu-erh, Pu'er, alpha-amylase or alpha-glucosidase. RESULTS: Six studies exploring inhibitory effects on alpha-glucosidase and seven on alpha-amylase were included for systemic review. Though results showed pu-erh tea has significant inhibitory effects on alpha-amylase and alpha-glucosidase, high heterogeneity was detected among studies included. CONCLUSIONS: High heterogeneity may be due to complex alterations of chemicals under different degrees of fermentation. More future studies are required to further identify principal bioactive component(s) at work.

Subscribing to Specimens, Cataloging Subscribed Specimens, and Assembling the First Phytogeographical Survey in the United States.

Throughout the late 1840s and the early 1850s, Harvard botanist Asa Gray (1810-1888) and his close friend George Engelmann (1809-1884) of St. Louis engaged themselves with recruiting men who sought to make a living by natural history collecting, sending these men into the field, searching for institutions and individuals who would subscribe to incoming collections, compiling catalogs, and collecting subscription fees. Although several botanists have noted Gray and Engelmann's bold experiment as having introduced America to a mode by which European naturalists had devised to organize scientific expeditions, historians of science have not taken the "subscription mode" seriously. I argue that it was specifically by undertaking the labor of cataloging species and charging subscription fees for the cataloged species that Gray established himself as a metropolitan botanist. One crucial consequence of Gray's rising profile was that he acquired sufficient "cataloging power" to secure his status as an authoritative cataloger of species, and as a kind of "mint" or "storehouse" (McOuat in Br J Hist Sci 34(1):1-28, 2001a) who produced well-pruned lists of American species to enable transactions between American and European botanists. But this essay is not focused on the Europeanization of American taxonomy. Drawing on work by scholars who place emphasis on how new forms of knowledge get produced when knowledge travels, my focus here is the evolution of the subscription mode when Gray and Engelmann adapted it to American natural history. My conclusion examines what historian of science Vanessa Heggie (Isis 105(2):318-334, 2014) identifies as the "danger of category dominance" in today's historiography of science and shows how a kind of "assemblage thinking" may help historians cope with this danger.

Citrate-Induced p85α⁻PTEN Complex Formation Causes G2/M Phase Arrest in Human Pharyngeal Squamous Carcinoma Cell Lines.

Citrate is a key intermediate of the tricarboxylic acid cycle and acts as an allosteric signal to regulate the production of cellular ATP. An elevated cytosolic citrate concentration inhibits growth in several types of human cancer cells; however, the underlying mechanism by which citrate induces the growth arrest of cancer cells remains unclear. The results of this study showed that treatment of human pharyngeal squamous carcinoma (PSC) cells with a growth-suppressive concentration of citrate caused cell cycle arrest at the G2/M phase. A coimmunoprecipitation study demonstrated that citrate-induced cell cycle arrest in the G2/M phase was associated with stabilizing the formation of cyclin B1-phospho (p)-cyclin-dependent kinase 1 (CDK1) (Thr 161) complexes. The citrate-induced increased levels of cyclin B1 and G2/M phase arrest were suppressed by the caspase-3 inhibitor Ac-DEVD-CMK and caspase-3 cleavage of mutant p21 (D112N). Ectopic expression of the constitutively active form of protein kinase B (Akt1) could overcome the induction of p21 cleavage, cyclin B1-p-CDK1 (Thr 161) complexes, and G2/M phase arrest by citrate. p85α-phosphatase and tensin homolog deleted from chromosome 10 (PTEN) complex-mediated inactivation of Akt was required for citrate-induced G2/M phase cell cycle arrest because PTEN short hairpin RNA or a PTEN inhibitor (SF1670) blocked the suppression of Akt Ser 473 phosphorylation and the induction of cyclin B1-p-CDK1 (Thr 161) complexes and G2/M phase arrest by citrate. In conclusion, citrate induces G2/M phase arrest in PSC cells by inducing the formation of p85α-PTEN complexes to attenuate Akt-mediated signaling, thereby causing the formation of cyclin B1-p-CDK1 (Thr 161) complexes.

Suppression of Akt-mediated HDAC3 expression and CDK2 T39 phosphorylation by a bichalcone analog contributes to S phase retardation of cancer cells.

Targeting cell cycle regulators has been a suggested mechanism for therapeutic cancer strategies. We report here that the bichalcone analog TSWU-CD4 induces S phase arrest of human cancer cells by inhibiting the formation of cyclin A-phospho (p)-cyclin-dependent kinase 2 (CDK2, threonine [Thr] 39) complexes, independent of mutant p53 expression. Ectopic expression of CDK2 (T39E), which mimics phosphorylation of the Thr 39 residue of CDK2, partially rescues the cells from TSWU-CD4-induced S phase arrest, whereas phosphorylation-deficient CDK2 (T39A) expression regulates cell growth with significant S phase arrest and enhances TSWU-CD4-triggered S phase arrest. Decreased histone deacetylase 3 (HDAC3) expression after TSWU-CD4 treatment was demonstrated, and TSWU-CD4 induced S phase arrest and inhibitory effects on cyclin A expression and CDK2 Thr 39 phosphorylation, while cyclin A-p-CDK2 (Thr 39) complex formation was suppressed by ectopic wild-type HDAC3 expression. The co-transfection of CDK2 (T39E) along with HDAC3 completely restored cyclin A expression, Thr 39-phosphorylated CDK2, cyclin A-p-CDK2 (Thr 39) complex formation, and the S phase population to normal levels. Protein kinase B (Akt) inactivation was required for TSWU-CD4-induced S phase cell cycle arrest, because constitutively active Akt1 blocks the induction of S phase arrest and the suppression of cyclin A and HDAC3 expression, CDK2 Thr 39 phosphorylation, and cyclin A-p-CDK2 (Thr 39) complex formation by TSWU-CD4. Taken together, our results indicate that TSWU-CD4 induces S phase arrest by inhibiting Akt-mediated HDAC3 expression and CDK2 Thr 39 phosphorylation to suppress the formation of cyclin A-p-CDK2 (Thr 39) complexes.

The double-edged sword of endoplasmic reticulum stress in uremic sarcopenia through myogenesis perturbation.

BACKGROUND: Sarcopenia is the age-related degeneration characterized with the decline of skeletal muscle mass, strength, and function. The imbalance of protein synthesis and degradation which jeopardizes immune, hormone regulation, and muscle-motor neuron connection is the main cause of sarcopenia. There is limited knowledge regarding molecular mechanism of sarcopenia. As the endoplasmic reticulum is the control centre of the protein syntheses and degradation, we hypothesized that endoplasmic reticulum stress and unfolded protein response (UPR) play an important in the development of sarcopenia. Understanding the sarcopenia molecular mechanisms may benefit the therapeutic diagnosis and treatment in the future. METHODS: Mouse myoblast C2C12 cells are exposed to designated time and concentration of indoxyl sulfate (IS), a uremic toxin of chronic kidney disease. The proliferation, differentiation, and the expression of atrogin 1 are examined. The protein and mRNA expression of IS treated-C2C12 cells are inspected to distinguish the role of ER stress and oxidative stress underlying the sarcopenia. RESULTS: Indoxyl sulfate inhibits myoblast differentiation. We demonstrate that as the number of multi-nuclei myotube decreased, the differentiation markers including myoD, myoG, and myosin heavy chain are also suppressed. Indoxyl sulfate inhibits myoblast proliferation and induces the myotubular atrophy marker atrogin-1 protein expression. Indoxyl sulfate stimulates eIF2α phosphorylation and XBP1 mRNA splicing in UPR. Interestingly, the oxidative stress is related to eIF2α phosphorylation but not XBP1 mRNA splicing. The eIF2α phosphorylation triggered by IS reduces myoD, myoG, and myosin heavy chain protein expression, which represents the anti-myogenic modulation on the early differentiation event. The XBP1 mRNA splicing induced by IS, however, is considered the adaptive response to restore the myogenic differentiation. CONCLUSIONS: Our studies indicated that the ER stress and UPR modulation are critical in the chronic kidney disease uremic toxin-accumulated sarcopenia model. We believe that UPR-related signals showed great potential in clinical application.

"Plants that Remind Me of Home": Collecting, Plant Geography, and a Forgotten Expedition in the Darwinian Revolution.

In 1859, Harvard botanist Asa Gray (1810-1888) published an essay of what he called "the abstract of Japan botany." In it, he applied Charles Darwin's evolutionary theory to explain why strong similarities could be found between the flora of Japan and that of eastern North America, which provoked his famous debate with Louis Agassiz (1807-1873) and initiated Gray's efforts to secure a place for Darwinian biology in the American sciences. Notably, although the Gray-Agassiz debate has become one of the most thoroughly studied scientific debates, historians of science remain unable to answer one critical question: How was Gray able to acquire specimens from Japan? Making use of previously unknown archival materials, this article scrutinizes the institutional, instrumental, financial, and military settings that enabled Gray's collector, Charles Wright (1811-1885), to travel to Japan, as well as examine Wright's collecting practices in Japan. I argue that it is necessary to examine Gray's diagnosis of Japan's flora and the subsequent debate about it from the viewpoint of field sciences. The field-centered approach not only unveils an array of historical significances that have been overshadowed by the analytical framework of the Darwinian revolution and the reception of Darwinism, but also places a seemingly domestic incident in a transnational context.

Better Overall Survival for Breast Cancer Patients by Adding Breast Ultrasound to Follow-Up Examinations for Early Detection of Locoregional Recurrence-A Survival Impact Study.

We retrospectively reviewed patient records to evaluate the effectiveness of our 15 y of ultrasound (US) surveillance of recurrent breast disease in comparison with mammography (MM) and clinical examination. From 4796 stage 0-III breast cancer patients who had received surgical treatment, we identified locoregional recurrence (LRR) in 161 patients. The mean age of the 161 patients was 48 y (27-82 y), and the mean follow-up interval was 77.2 mo (11-167 mo). The methods of LRR detection, sites of LRR and overall survival (OS) were examined. Multivariate Cox survival analysis showed significantly better survival in groups detected by US (hazard ratio = 0.6, p = 0.042). The 10-y LRR OS by detection types for US (n = 69), clinical examination (n = 78) and MM (n = 8) were 58.5%, 33.1% and 100%, respectively (p = 0.0004). US was seen with better OS associated with the effective early detection of non-palpable LRR breast cancer, which is mostly not detectable on MM.

The learning curve of laparoscopic liver resection after the Louisville statement 2008: Will it be more effective and smooth?

BACKGROUND: Laparoscopic liver resection (LLR) has been proven to be feasible and safe. However, it is a difficult and complex procedure with a steep learning curve. The aim of this study was to evaluate the learning curve of LLR at our institutions since 2008. METHODS: One hundred and twenty-six consecutive LLRs were included from May 2008 to December 2014. Patient characteristics, operative data, and surgical outcomes were collected prospectively and analyzed. RESULTS: The median tumor size was 25 mm (range 5-90 mm), and 96 % of the resected tumors were malignant. 41.3 % (52/126) of patients had pathologically proven liver cirrhosis. The median operation time was 216 min (range 40-602 min) with a median blood loss of 100 ml (range 20-2300 ml). The median length of hospital stay was 4 days (range 2-10 days). Six major postoperative complications occurred in this series, and there was no 90-day postoperative mortality. Regarding the incidence of major operative events including operation time longer than 300 min, perioperative blood loss above 500 ml, and major postoperative complications, the learning curve [as evaluated by the cumulative sum (CUSUM) technique] showed its first reverse after 22 cases. The indication of laparoscopic resection in this series extended after 60 cases to include tumors located in difficult locations (segments 4a, 7, 8) and major hepatectomy. CUSUM showed that the incidence of major operative events proceeded to increase again, and the second reverse was noted after an additional 40 cases of experience. Location of the tumor in a difficult area emerged as a significant predictor of major operative events. CONCLUSIONS: In carefully selected patients, CUSUM analysis showed 22 cases were needed to overcome the learning curve for minor LLR.

Sonographic elastography improves the sensitivity and specificity of axilla sampling in breast cancer: a prospective study.

We describe a study to determine whether elastography of axillary lymph nodes (LNs) combined with B-mode ultrasound (US) is capable of differentiating the benign from the metastatic state in patients with breast cancer. B-mode US, elastography and fine-needle aspiration of 90 axillary lymph nodes from 89 female patients with breast cancer are described in this report. Five elastographic patterns were observed as defined by the percentages of high elasticity according to pattern of distribution and degree of hardness of the target LNs. B-mode US and elastography scores were combined to give the final scores. Sensitivity and specificity were 80% and 88%, respectively, for B-mode US alone, 86% and 90% for elastography alone and 84% and 98% for the combined assessment to differentiate the benign from the malignant state. The combination of B-mode US and elastography is capable of identifying metastatic axillary LNs from benign enlargement in patients with breast cancer.