[Expression of Apelin and Snail protein in breast cancer and their prognostic significance].

Objective: To investigate the expression of Apelin and Snail proteins in breast cancer and their relationship with the clinicopathological features and prognosis. Methods: The expression of Apelin and Snail proteins was detected by immunohistochemistry in 89 cases of breast cancer and 50 cases of mammary adenosis collected from January to June in 2008 at Fujian Cancer Hospital; the expression was correlated with the clinicopathological features and outcome of the patients. Results: Apelin and Snail were expressed in 42 cases(47.2%)and 36 cases(40.4%)of breast cancers, respectively, and the expression was higher than that of control group (P<0.01). The expression of Apelin was positively correlated with Snail (r=0.230, P<0.05). Apelin expression was associated with lymph node metastasis and TNM staging(P<0.05). Snail expression was associated with lymph node metastasis(P<0.05). Kaplan-Meier survival curve showed that the prognosis of Apelin positive group was worse than that of Apelin negative group (P<0.01). There was no significant difference in prognosis between Snail negative and positive groups (P>0.05). The prognosis of Apelin and Snail in both positive groups was worse than that of Apelin and Snail both negative groups (P<0.01). Multivariate COX regression analysis showed that Apelin and TNM staging could be used as independent prognostic factors for breast cancer (P<0.05). Conclusions: Apelin and Snail are highly expressed in breast cancer, and associated with lymph node metastasis and TNM stage. There is a positive correlation between Apelin and Snail expression, which may suggest a role in breast carcinogenesis. The prognosis of breast cancer with expression of Apelin and co-expression of Apelin and Snail is poor. Therefore, Apelin may be used as an effective indicator to evaluate the prognosis of breast cancer patients.

Two-dimensional electronic transport and surface electron accumulation in MoS2.

Because the surface-to-volume ratio of quasi-two-dimensional materials is extremely high, understanding their surface characteristics is crucial for practically controlling their intrinsic properties and fabricating p-type and n-type layered semiconductors. Van der Waals crystals are expected to have an inert surface because of the absence of dangling bonds. However, here we show that the surface of high-quality synthesized molybdenum disulfide (MoS2) is a major n-doping source. The surface electron concentration of MoS2 is nearly four orders of magnitude higher than that of its inner bulk. Substantial thickness-dependent conductivity in MoS2 nanoflakes was observed. The transfer length method suggested the current transport in MoS2 following a two-dimensional behavior rather than the conventional three-dimensional mode. Scanning tunneling microscopy and angle-resolved photoemission spectroscopy measurements confirmed the presence of surface electron accumulation in this layered material. Notably, the in situ-cleaved surface exhibited a nearly intrinsic state without electron accumulation.

The relationship between high-density lipoprotein cholesterol levels and arterial stiffness in a Taiwanese population.

BACKGROUND AND AIMS: There are few studies on the association between HDL-C levels and arterial stiffness (AS). HDL-C levels vary in males and females, and it is not clear whether the relationship between HDL-C levels and AS is influenced by gender. The purpose of this study was to investigate gender differences in the association between HDL-C levels and AS in adults. METHODS AND RESULTS: After excluding subjects using lipid-lowering agent, 7254 subjects were enrolled. The AS was assessed by measuring the brachial-ankle pulse wave velocity (baPWV) value. The quartiles of HDL-C were <38, 38-45, 45-53 and >53 mg/dL in men and <48, 48-57, 57-69 and >68 mg/dL in women, respectively. In subjects aged <50 years, none of the HDL-C quartiles were associated with baPWV values. In subjects aged ≥50 years, the highest quartile of HDL-C (beta: -37.57, 95% CI: -61.61 to -13.54) was negatively related to baPWV values. When considering gender difference in subjects aged ≥50 years, the highest quartile of HDL-C (Q4 beta: -57.22, 95% CI: -95.63 to -18.81) was inversely associated with baPWV values in women, but none of the HDL-C quartiles were related to baPWV values in men. CONCLUSIONS: A high HDL-C level was associated with a lower risk of AS in subjects aged ≥50 years in women but not in men, although this relationship was not apparent in subjects aged <50 years. The association between HDL-C level and AS is thus influenced by gender in people aged ≥50 years.

[Microcystic, elongated and fragmented invasive pattern in endometrial adenocarcinoma: a clinicopathologic analysis of 72 cases].

Objective: To investigate the clinicopathologic features of microcystic, elongated and fragmented (MELF) pattern invasion of endometrial adenocarcinoma. Methods: HE and immunohistochemistry staining method were used to analysis morphologic features and immunophenotype of 72 patients of endometrial adenocarcinoma with MELF pattern invasion, and chi-square test was used to analysis the clinicopathologic features. Results: The mean age of 72 patients was 54 years (40 to 70 years). Thirty-two patients were pre-menopausal and 40 were post-menopausal. According to the FIGO staging system (2014), 32 cases(44.4%)were at stage Ⅰ, 22 cases(30.6%)at stage Ⅱ, 17 cases(23.6%)at stage Ⅲ and 1 case(1.4%) at stage Ⅳ. Microscopically, MELF invasion showed microcystic, elongated slit-like or fragmented glands in myometrium and their lining cells usually were cube or flat, as well as the single or clusters of eosinophilic tumor cells mimicking histocytes. In addition, a fibromyxoid or inflammatory stromal response was often present.Immunohistochemical staining showed that MELF invasion was positive for p16, CA125 and CA19-9, but negative for ER, PR and p53.Compared with non-MELF pattern invasion, significant differences were noted in menopause pausimenia, FIGO stages, deep invasion into myometrium, lymph metastasis, lymphovascular space invasion (LVSL), serum CA125 and CA19-9 in patients with MELF pattern invasion (all P<0.05). Conclusions: MELF pattern invasion of endometrial adenocarcinoma is characterized by advanced FIGO stage, deep myoinvasion, high metastasis rate to lymph node and LVSL. Pathologists should recognize the MELF invasion and evaluate the depth of myometrium of infiltration and LVSL with special attention to the presence of MELF invasion with necessary immunohistochemistry for more accurate pathological diagnosis.

Changing roles of computed tomography in diagnosing acute appendicitis in emergency rooms.

BACKGROUND: We used the Taiwan National Health Insurance Database for analysis and statistics to investigate the role of computed tomography (CT) in diagnosing acute appendicitis. MATERIALS AND METHODS: All 10 046 patients with acute appendicitis were selected and categorized into two groups based on those who did and did not receive CT 3 days before acute appendicitis diagnosis: non-CT and CT groups. A noteworthy outcome was the incidence of peritonitis within 90 days after diagnosis of acute appendicitis. RESULTS: The rate of using CT for patients with acute appendicitis increased considerably from 7.9% to 52.9% from 2000 to 2010. The peritonitis incidence rates were 3.54% and 10.7% in the non-CT and CT groups, respectively. Patients who received CT on the same day exhibited a 3.8-fold higher risk of peritonitis than did those in the non-CT group. Those who underwent CT before diagnosis of acute appendicitis exhibited no significant difference of peritonitis risk when compared with those in the non-CT group. The CT group patients were hospitalized 2.19 days longer than the non-CT group patients. Patients who received CT before and on the same day were hospitalized 1.31 and 2.43 days longer than those who did not undergo CT. CONCLUSION: Patients who underwent CT exhibited higher risks of peritonitis and longer hospital stays compared with those who did not. Moreover, patients who received CT on the same day of operation exhibited a higher risk of peritonitis than those who underwent CT 1 or 2 days before operation.

Increased risk of chronic fatigue syndrome following herpes zoster: a population-based study.

Chronic fatigue syndrome (CFS) is a complex disorder accompanied by unexplainable persistent fatigue, in which several etiological factors exist, such as viral infections. Using the National Health Insurance Research Database (NHIRD) of Taiwan, this study evaluated the association between herpes zoster (HZ) infection and the risk of CFS, and examined the possibility of patients developing postviral fatigue effects, including the possibility of developing other unexplainable chronic fatigue conditions. In this prospective cohort study using the NHIRD, we identified 9,205 patients with HZ infection [ICD-9 (International Classification of Disease, Ninth Revision), code 053] and 36,820 patients without HZ infection (non-HZ) from 2005 to 2007, and followed up to the end of 2010. The incidence rate of CFS was higher in the HZ cohort than in the non-HZ cohort (4.56 vs. 3.44 per 1,000 person-years), with an adjusted hazard ratio of 1.29 [95 % confidence interval (CI) = 1.09-1.53]. It was shown that the risk of CFS without comorbidity for each patient increased from 1.25- to 1.36-fold between the CFS and non-CFS cohorts; with long-term follow-up, the HZ cohort showed a significantly higher cumulative incidence rate of developing CFS than the non-HZ patients. We propose that patients with chronic fatigue might exist in a subset of patients that would be associated with HZ infection. The actual mechanism of development of CFS that is attributed to HZ infection remains unclear. The findings of this population cohort study provide pivotal evidence of postviral fatigue among patients with HZ infection.

Increased risk of lichen simplex chronicus in people with anxiety disorder: a nationwide population-based retrospective cohort study.

BACKGROUND: The cingulate cortex is the main area in the brain involved in pruritus processing and is deactivated after scratching. Lichen simplex chronicus (LSC) is a common pruritic skin disorder characterized by skin lichenification following excessive scratching. Psychological factors may contribute to both the development and persistence of LSC. OBJECTIVES: To estimate the hazard ratio (HR) of LSC in people with anxiety disorders compared with the general population. METHODS: In this nationwide population-based retrospective cohort study we identified a total of 69 386 people, who formed the anxiety cohort, by using the Taiwan National Health Insurance Research Database from 2000 to 2009. The comparison cohort was composed of randomly selected people frequency matched for age (within 5-year intervals), sex and index date (the date of anxiety diagnosis) based on a 1 : 2 ratio. The risk of LSC was estimated as HRs and 95% confidence intervals (CIs) using the Cox proportional hazards model. RESULTS: After adjusting for age, sex and LSC-associated comorbidities, the people with anxiety had a 1·41-fold greater risk of developing LSC compared with the people in the comparison cohort (HR 1·41, 95% CI 1·30-1·52, P < 0·0001). In particular, individuals with obsessive-compulsive disorder had a significantly increased risk of developing LSC (HR 1·72, 95% CI 1·03-2·88, P = 0·0395). CONCLUSIONS: This study demonstrates that having an anxiety disorder is associated with an increased risk of LSC. Psychological factors were found to contribute to LSC. We recommend combining the management of LSC and psychological disorders to achieve favourable outcomes.

Electroacupuncture and Acupuncture Promote the Rat's Transected Median Nerve Regeneration.

Background. Acupuncture and electroacupuncture treatments of damaged nerves may aid nerve regeneration related to hindlimb function, but the effects on the forelimb-related median nerve were not known. Methods. A gap was made in the median nerve of each rat by suturing the stumps into silicone rubber tubes. The influences of acupuncture and electroacupuncture treatments on transected median nerve regeneration were evaluated from morphological, electrophysiological, and functional angles. Results. Morphologically, the group receiving acupuncture and electroacupuncture treatments had larger total nerve area and blood vessel number compared with the controls. Electrophysiologically, the group receiving electroacupuncture had significantly larger amplitude and larger area of the evoked muscle action potentials compared with the controls. Functionally, the acupuncture and electroacupuncture treatments enhanced the injured paw's ability to regain its grasping power and resulted in a faster efficiency to a new bilateral balance. Conclusion. Our findings provide multiapproach evidence of the efficacy of acupuncture and electroacupuncture treatments to the regeneration of median nerve. Indeed, acupuncture and electroacupuncture appear to have positive effects on the regeneration processes. This platform is beneficial to further study the clinical application of acupuncture and electroacupuncture alternative treatments on nerve-injured patients.

Variations in bone density at dental implant sites in different regions of the jawbone.

The survival rate of dental implants is markedly influenced by the quality of the bone into which they are placed. The purpose of this study was to determine the trabecular bone density at potential dental implant sites in different regions of the Chinese jawbone using computed tomography (CT) images. One hundred and fifty-four potential implant sites (15 in the anterior mandible, 47 in the anterior maxilla, 55 in the posterior mandible, and 37 in the posterior maxilla) were selected from the jawbones of 62 humans. The data were subjected to statistical analysis to determine any correlation between bone density (in Hounsfield units, HU) and jawbone region using the Kruskal-Wallis test. The bone densities in the four regions decreased in the following order: anterior mandible (530 +/- 161 HU, mean +/- s.d.) approximately equal anterior maxilla (516 +/- 132 HU) > posterior mandible (359 +/- 150 HU) approximately equal posterior maxilla (332 +/- 136 HU). The CT data demonstrate that trabecular bone density varies markedly with potential implant site in the anterior and posterior regions of the maxilla and mandible. These findings may provide the clinician with guidelines for dental implant surgical procedures (i.e., to determine whether a one-stage or a two-stage protocol is required).

Computer-aided diagnosis in two-phase 201Tl-SPECT of thoracic lesions.

AIM: The retention index, a traditionally quantitative analysis of two-phase (201)Tl single photon emission computed tomography (SPECT) of the chest, is manually calculated by experienced physicians from comparable 2-D ROI. However, a 3-D ROI would provide more information than a 2-D ROI extracted from a single frame of SPECT. We propose a new diagnostic system, computer-aided diagnosis (CAD), to automatically detect suspicious lesions as 3-D objects on chest (201)Tl-SPECT, and assist the physician in interpreting these images. PATIENTS, METHODS: Seventy patients with thoracic lesions and confirmed diagnoses were enrolled to test this automatic CAD system. The reliability of the CAD system in detecting lesions as 3-D objects was compared to the 2-D ROI of (201)Tl-SPECT found by the manually visualized method. Furthermore, we also proposed a novel index, the retention index using the heart (RIH), to differentiate high retention (slow clearance, increasing target to heart ratio) as a criterion for a malignant lesion, from low retention (faster clearance, small or no increase of the target to heart ratio) for benign lesions. RESULTS: The CAD system can achieve a detection rate of 100% in automatically searching for thoracic lesions in (201)Tl-SPECT. In diagnostic performance, the CAD system with the RIH of comparable 3-D objects has an area under the ROC curve of 0.86, higher than the 0.78 of the traditional RI method (p=0.198). CONCLUSION: The CAD system of two-phase (201)Tl-SPECT is a promising tool for detecting and diagnosing thoracic lesions with a diagnostic accuracy of 0.81.

ELM1 is required for multidrug resistance in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, transcription of several drug transporter genes, including the major transporter gene PDR5, has been shown to peak during mitosis. The significance of this observation, however, remains unclear. PDR1 encodes the primary transcription activator of multiple drug transporter genes in S. cerevisiae, including PDR5. Here, we show that in synchronized PDR1 and pdr1-3 (multidrug resistant) strains, cellular efflux of a known substrate of ATP-binding-cassette transporters, doxorubicin (a fluorescent anticancer drug), is highest during mitosis when PDR5 transcription peaks. A genetic screen performed to identify regulators of multidrug resistance revealed that a truncation mutation in ELM1 (elm1-300) suppressed the multidrug resistance of pdr1-3. ELM1 encodes a serine/threonine protein kinase required for proper regulation of multiple cellular kinases, including those involved in mitosis, cytokinesis, and cellular morphogenesis. elm1-300 as well as elm1Delta mutations in a pdr1-3 strain also caused elongated bud morphology (indicating a G2/M delay) and reduction of PDR5 transcription under induced and noninduced conditions. Interestingly, mutations in several genes functionally related to ELM1, including cla4Delta, gin4Delta, and cdc28-C127Y, also caused drastic reductions in drug resistance and PDR5 transcription. Collectively, these data show that ELM1, and genes encoding related serine/threonine protein kinases, are required for regulation of multidrug resistance involving, at least in part, control of PDR5 transcription.

TFIID and Spt-Ada-Gcn5-acetyltransferase functions probed by genome-wide synthetic genetic array analysis using a Saccharomyces cerevisiae taf9-ts allele.

TAF9 is a TATA-binding protein associated factor (TAF) conserved from yeast to humans and shared by two transcription coactivator complexes, TFIID and SAGA. The essentiality of the TAFs has made it difficult to ascertain their roles in TFIID and SAGA function. Here we performed a genomic synthetic genetic array analysis using a temperature-sensitive allele of TAF9 as a query. Results from this experiment showed that TAF9 interacts genetically with: (1) genes for multiple transcription factor complexes predominantly involving Mediator, chromatin modification/remodeling complexes, and regulators of transcription elongation; (2) virtually all nonessential genes encoding subunits of the SWR-C chromatin-remodeling complex and both TAF9 and SWR-C required for expressing the essential housekeeping gene RPS5; and (3) key genes for cell cycle control at the G1/S transition, as well as genes involved in cell polarity, cell integrity, and protein synthesis, suggesting a link between TAF9 function and cell growth control. We also showed that disruption of SAGA by deletion of SPT20 alters histone-DNA contacts and phosphorylated forms of RNA polymerase II at coding sequences. Our results raise the possibility of an unappreciated role for TAF9 in transcription elongation, perhaps in the context of SAGA, and provide further support for TAF9 involvement in cell cycle progression and growth control.

Classification of the guava wilt fungus Myxosporium psidii, the palm pathogen Gliocladium vermoesenii and the persimmon wilt fungus Acremonium diospyri in Nalanthamala.

Psidium guajava wilt is known from South Africa, Malaysia and Taiwan. The fungus causing this disease, Myxosporium psidii, forms dry chains of conidia on surfaces of pseudoparenchymatous sporodochia, which develop in blisters on bark. Similar sporodochia are characteristic of Nalanthamala madreeya, the type species of Nalanthamala. Nalanthamala, therefore, is the appropriate anamorph genus for Myxosporium psidii, while Myxosporium is a nomen nudum (based on M. croceum). For M. psidii the combination Nalanthamala psidii is proposed. Nalanthamala psidii, the palm pathogen Gliocladium (Penicillium) vermoesenii, another undescribed anamorphic species from palm, two species of Rubrinectria and the persimmon pathogen Acremonium diospyri are monophyletic and belong to the Nectriaceae (Hypocreales) based on partial nuclear large subunit ribosomal DNA (LSU rDNA) analyses. Rubrinectria, therefore, is the teleomorph of Nalanthamala, in which the anamorphs are classified as N. vermoesenii, N. diospyri or Nalanthamala sp. Nalanthamala squamicola, the only other Nalanthamala species, has affinities with the Bionectriaceae and is excluded from this group. Rubrinectria/Nalanthamala species form dimorphic conidiophores and conidia in culture. Fusiform, cylindrical, or allantoid conidia arise in colorless liquid heads on acremonium-like conidiophores; ovoidal conidia with somewhat truncated ends arise in long, persistent, dry chains on penicillate conidiophores. No penicillate but irregularly branched conidiophores were observed in N. diospyri. Conidia of N. psidii that are held in chains are shorter than those of N. madreeya, of which no living material is available. Nalanthamala psidii and N. diospyri are pathogenic specifically to their hosts. They form pale yellow to pale orange or brownish orange colonies, respectively, and more or less white conidial masses. Most strains of Rubrinectria sp., Nalanthamala sp. and N. vermoesenii originate from palm hosts, form mostly greenish or olive-brown colonies and white-to-salmon conidial masses. They form a monophyletic clade to which Nalanthamala psidii and N. diospyri are related based on analyses of the internal transcribed spacer regions and 5.8S rDNA (ITS rDNA), LSU rDNA, and partial beta-tubulin gene. Few polymorphic sites in the ITS rDNA and beta-tubulin gene indicate that Nalanthamala psidii comprises two lineages, one of which has been detected only in South Africa.

Division of labor among the yeast Sol proteins implicated in tRNA nuclear export and carbohydrate metabolism.

SOL1, the founding member of the S. cerevisiae SOL family, was previously identified as a multi-copy suppressor of the los1 defect in tRNA-mediated nonsense suppression. Here we report that the four-member SOL family is not essential and that individual family members appear to have distinct functions. SOL1-SOL4 are homologous to genes encoding 6-phosphogluconolactonase (6Pgl) involved in the pentose phosphate pathway. Both Sol3p and Sol4p affect this activity. However, Sol4p does not act as a los1 multi-copy suppressor. In contrast, neither Sol1p nor Sol2p, both of which correct the los1 defect in nonsense suppression, possess detectable 6Pgl activity. Rather, Sol1p and Sol2p appear to function in tRNA nuclear export as sol1 and sol2 mutants possess elevated levels of nuclear tRNA. Members of the Sol protein family appear to have different subcellular distributions. Thus, Sol3p and Sol4p likely function in carbohydrate metabolism, while Sol1p and Sol2p appear to have roles in tRNA function and nuclear export, thereby defining an unusual protein family whose individual members are biochemically distinct and spatially dispersed.

On the mechanism of constitutive Pdr1 activator-mediated PDR5 transcription in Saccharomyces cerevisiae: evidence for enhanced recruitment of coactivators and altered nucleosome structures.

Drug resistance as a result of overexpression of drug transporter genes presents a major obstacle in the treatment of cancers and infections. The molecular mechanisms underlying transcriptional up-regulation of drug transporter genes remains elusive. Employing Saccharomyces cerevisiae as a model, we analyzed here transcriptional regulation of the drug transporter gene PDR5 in a drug-resistant pdr1-3 strain. This mutant bears a gain-of-function mutation in PDR1, which encodes a transcriptional activator for PDR5. Similar to the well studied model gene GAL1, we provide evidence showing that PDR5 belongs to a group of genes whose transcription requires the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex. We also show that the drugindependent PDR5 transcription is associated with enhanced promoter occupancy of coactivator complexes, including SAGA, Mediator, chromatin remodeling SWI/SNF complex, and TATA-binding protein. Analyzed by chromatin immunoprecipitations, loss of contacts between histones and DNA occurs at both promoter and coding sequences of PDR5. Consistently, micrococcal nuclease susceptibility analysis revealed altered chromatin structure at the promoter and coding sequences of PDR5. Our data provide molecular description of the changes associated with constitutive PDR5 transcription, and reveal the molecular mechanism underlying drug-independent transcriptional up-regulation of PDR5.

Mechanisms of TfR-mediated transcytosis and sorting in epithelial cells and applications toward drug delivery.

Transferrin receptor has been an important protein for many of the advances made in understanding the intricacies of the intramolecular sorting pathways of endocytosed molecules. The unique internalization and recycling functions of transferrin receptor have also made it an attractive choice for drug targeting and delivery of large protein-based therapeutics and toxins. Recent advances in elucidating the role of the intracellular controllers of transferrin recycling and sorting, such as Rab proteins and their effectors, have led to enhancement of transferrin receptor as a drug delivery vehicle. This review focuses on the use of transferrin receptor as an agent for facilitating drug delivery and targeting, and the role that mechanisms of transferrin receptor sorting and transcytosis play in these events.