Search

International audience

Background Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an antibody–drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020. Patients and methods We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2−) HR+/HER2− mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety. Results Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% [95% confidence interval (CI), 19.5%–45.6%; 17 partial responses]; median DOR was 8.7 months (95% CI 3.7–12.7), median PFS was 5.5 months (95% CI 3.6–7.6), and median OS was 12 months (95% CI 9.0–18.2). Conclusions SG shows encouraging activity in patients with pretreated HR+/HER2− mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339). Trial registration ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552

We give an extension of Hua’s inequality for C*-valued norm in pre-Hilbert C*-modules setting. As its applications, some known and new generalizations of Hua’s inequality are deduced. In particular, we establish the connection between C*-valued norm triangle inequality and C*-valued norm Hua’s inequality. We also present some operator versions of Hua’s inequality on Hilbert spaces. As a consequence, we obtain various forms of Hua’s inequality. Moreover, we indicate that for our operator, Hua’s inequality is equivalent to operator convexity of a given continuous real function.

Power systems are experiencing massive changes in their generation patterns with increasing penetration of decentralised renewable generation and decommissioning of thermal plants. Such changes in generation patterns will bring significant challenges to the black start arrangement. Conventional black start process relies on large thermal plants connected at the transmission level to energise the system using a "top-down" approach. This may no longer be adequate or applicable in future networks due to the closure of most thermal plants. This paper will investigate the feasibility of using Distributed Energy Resources (DERs) to provide a "bottom-up" black start approach. Compared with the conventional approach, using DERs for black start has potential advantages of reduced restoration time and more flexible recovery procedure. In this paper, a comprehensive review of the existing black start studies utilising DERs will be provided. Additionally, several case studies using a distribution network model containing multiple resources such as wind, micro-hydro generator, and energy storage will be presented to demonstrate the feasibility of providing black start capability by DERs. Furthermore, the associated technical issues that need to be considered to enable such a black start approach will also be discussed, along with feasible solutions and suggestions for further investigation.

Background: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes. Patients and methods: Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline. Results: Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations. Conclusions: SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup., SCOPUS: ar.j, info:eu-repo/semantics/published

The difficulty of transanal total mesorectal excision (TME) is to find the correct dissection plane of perirectal space. As a complex new surgical procedure, the fascial anatomic landmarks of transanal approach operation are more likely to be ignored. It is often found that dissection plane is false after the secondary injury occurs during the operation, which results in the damage of pelvic autonomic nerves. Meanwhile, the mesorectum is easily damaged if the dissection plane is too close to the rectum. Thus, the safety of oncologic outcomes could be limited by difficulty achieving adequate TME quality. The promotion and development of the theory of perirectal fascial anatomy provides a new thought for researchers to design a precise approach for transanal endoscopic surgery. Transanal total mesorectal excision based on fascial anatomy offers a solution to identify the transanal anatomic landmarks precisely and achieves pelvic autonomic nerve preservation. In this paper, the authors focus on the surgical experience of transanal total mesorectal excision based on the theory of perirectal fascial anatomy, and discuss the feature of perirectal fascial anatomy dissection and technique of pelvic autonomic nerve preservation during transanal approach operation.经肛全直肠系膜切除术的难点在于寻找直肠周围间隙的正确分离平面，作为一种复杂的新术式，实施过程中经肛操作的筋膜解剖标志容易被忽略，待出现术中副损伤时才发现游离平面有误，从而导致盆腔自主神经受损；若是游离平面过于靠近直肠，可能造成直肠系膜受损，则无法实现完整的TME标本质量，从而导致肿瘤学安全无法得到保证。膜解剖理论的推动与发展，为经肛腔镜手术的精准实施提供了一种新的思路。基于膜解剖的经肛全直肠系膜切除术可精确识别经肛操作解剖标志并加以神经保护，为上述难题提供了一个解决方案。本中心以直肠周围筋膜解剖的理论为基础，结合经肛腔镜全直肠系膜切除手术经验，探讨经肛操作中直肠周围筋膜分离的特点和盆腔自主神经保护的技巧。.

Epidural catheters are often used in the provision of surgical anaesthesia and analgesia. These catheters need to be removed after a certain period, but difficulties may be encountered during this process. We present a case of difficult epidural catheter removal in an elderly woman who had undergone surgery for reduction and internal fixation of a comminuted intertrochanteric fracture at the left femur under combined spinal epidural anaesthesia. Anaesthesia was satisfactory during the operation; however, initial attempts to remove the catheter at the end of the procedure was met with significant resistance. Normal saline (5 ml) was injected through the catheter without difficulty, suggesting that the catheter was likely trapped and compressed but not obstructed. A nickel/titanium memory alloy suture was used as a guidewire to remove the catheter without damaging it. This case was analysed subsequently, and the management of future problematic removals is discussed herein. This article aims to raise awareness of, and to explore techniques for managing difficult epidural catheter removal.

Background This study evaluated the impact of the adapted version of the Respecting Choices® The Living Matters Advance Care Planning (ACP) facilitator training programme on trainees’ attitudes on facilitation 6 months post-training. Setting and participants Two hundred and twenty-one healthcare professionals consisting of doctors, nurses, medical social workers from different training venues in Singapore participated in the first phase of the study (pre- and post) of which 107 participated in the second phase 6 months later (follow-up). Methods Participants self-rated their attitudes, beliefs and behavioural intentions through surveys at three time points in an evaluation design that utilised repeated measures one-way ANOVA (pre-, post-, follow-up). Between-group differences were also examined using independent t-test. Results At follow-up, mean scores increased significantly in understanding, confidence, and competence. Changes in effect sizes were large. Although trainees continued to think that ACP is emotionally draining for facilitators, more than before, facilitation experience was considered pleasant for themselves with the positive change significant and moderate in effect size. Those who had experience completing/initiating ACP significantly held more positive views than those who did not. Conclusions The ACP facilitator training programme had lasting effects on enhancing the understanding, competence, and confidence of trainees. Importantly, findings showed that experience in actual facilitation within 6 months after training was important and giving trainees opportunities to facilitate is recommended.

Additional file 2. Post-course questionnaire.

Additional file 1. Pre-course questionnaire.

Additional file 3. Follow-up questionnaire.

Background Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. Patients and methods Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. Results In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). Conclusions SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.

Persistent trigeminal artery (PTA) originates from the posterior bend or lateral wall of the intra-cavernous carotid artery and is the most common occurring type of remnant primitive fetal arteries. In literature, there is limited number of reports on migraine-cephalgia (MC) associated with coexisting PTA. The primitive anastomose arteries that fully belong to the intracranial arterial vascular system are not supposed to perform any supportive functional activity; usually they are subjected to normal biological decay caused by the aging process and metabolic dysfunctions. The hypothesis suggests that these primitive fetal arteries such as PTA may not undergo a fast and structural deterioration but they might be active contributors to a series of mechanisms that can cause a variety of idiopathic complaints. Consequently this would bring a different therapeutic approach other than their surgical removal, which is the accepted option today as a solution for these problems. In this case report, a chronic unilateral MC due to coexisting PTA adjacent to trigeminal nerve is presented. The caliber and location of the PTA was confirmed by a CT-Angiography. The MC treatment was achieved by administration of bio-identical testosterone, human placenta extract (HPE), b-nicotinamide adenine dinucleotide (NADH) and low dose amlopidine.

Extracellular vesicles (EVs) play important roles in cell-cell communication. In budding yeast (Saccharomyces cerevisiae), EVs function as carriers to transport cargo proteins into the periplasm for storage during glucose starvation. However, intracellular organelles that synthesize these EV-associated cargo proteins have not been identified. Here, we investigated whether cytoplasmic organelles—called intracellular vesicle clusters (IVCs)—serve as sites for the synthesis of proteins targeted for secretion as EV-associated proteins. Using proteomics, we identified 377 IVC-associated proteins in yeast cells grown under steady-state low-glucose conditions, with the largest group being involved in protein translation. Isolated IVCs exhibited protein synthesis activities that required initiation and elongation factors. We have also identified 431 newly synthesized proteins on isolated IVCs. Expression of 103Q-GFP, a foreign protein with a long polyglutamine extension, resulted in distribution of this protein as large puncta that co-localized with IVC markers, including fructose-1,6-bisphosphatase (FBPase) and the vacuole import and degradation protein Vid24p. We did not observe this pattern in cycloheximide-treated cells or in cells lacking VID genes, required for IVC formation. The induction of 103Q-GFP on IVCs adversely affected total protein synthesis in intact cells and on isolated IVCs. This expression also decreased levels of EV-associated cargo proteins in the extracellular fraction without affecting the number of secreted EVs. Our results provide important insights into the functions of IVCs as sites for the synthesis of EV-associated proteins targeted for secretion to the periplasm.

Exosomes are small vesicles secreted by a variety of cell types under physiological and pathological conditions. When Saccharomyces cerevisiae are grown in low glucose, small vesicles carrying more than 300 proteins with diverse biological functions are secreted. Upon glucose addition, secreted vesicles are endocytosed that requires cup-shaped organelles containing the major eisosome protein Pil1p at the rims. We aim to identify genes that regulate the function of cup-shaped organelles in vesicle endocytosis. In cells lacking either VID27 or VID21, Pil1p distribution was altered and cup-shaped organelles became elongated with narrower openings. Change in shape reduced the number of vesicles in the deeper areas and impaired vesicle endocytosis. Vid21p and Vid27p were localized to vesicle clusters and interacted with other Vid proteins. In the absence of these genes, these vesicles failed to aggregate and were secreted. Vid21p and Vid27p are required for the aggregation and retention of vesicles that contain Vid proteins in the cytoplasm. Increased vesicles near the plasma membrane in mutant strains correlate with an increased Pil1p movement resulting in the fusion of cup-shaped organelles. We conclude that the shape of vesicle-containing organelles is critical for their functions in vesicle endocytosis.

1例以"注意力不集中"为主诉的9岁患儿表现为注意缺陷、认知功能损害、共济失调快速进展，结合临床表现、辅助检查及基因检测结果，诊断为肾上腺脑白质营养不良。该类患儿早期症状易与注意缺陷多动障碍混淆，儿科医师需注意鉴别。.

Due to the changing nature of power systems-with reduced electrical inertia and the prevalence of smaller controllable power resources rather than large generators-new control approaches are required to mitigate disturbances. Ubiquitous measurements and communications networks can be leveraged to accelerate and provide a targeted, real-time response in such future systems. However, autonomous control of power systems requires dependable measurements. This paper provides a review of state of the art approaches to real-time power system control using synchrophasor measurements. In particular, examples are given involving recent developments in frequency regulation. Through a case study, it is shown how laboratories can be linked using Software-Defined Networking technologies to conveniently share resources in order to realistically and comprehensively validate synchrophasor-based control systems.

During the crack propagation, crack tip contains stress odd singularity and has specific yield range. As the cycling loading continuing, the crack grows in the plastic zone. So the plastic zone is crucial to crack propagation action. In this paper, the crack propagation route was observed in different microstrctures, the deformation characteristic of plastic zone was analyzed for equiaxed structure and lamellar structure. The results show that crack propagation path is more straighter in equiaxed structure than that in lamellar structure. There were more tiny cracks near the crack surface in the lamellar structure during the crack growth, which shows that lamellar structure has a bigger plastic zone during the deformation.The plastic deformation need absorb the energy, which hinders the crack propagation.

BACKGROUND: The highly efficient production of parthenogenetic embryos from vitrified porcine in vitro matured oocytes has become essential for biotechnology and biomedicine research.To investigate the survival and parthenogenetic development of oocytes vitrified before or after electric activation.The vitrified oocytes were parthenogenetically activated at 0, 0.5, 1, 2 and 4 h post warming (h.p.w.), and fresh oocytes were vitrified at 0, 0.5, 1, 2 and 4 h post electric activation (h.p.a.).In comparison with non-vitrified oocytes, the rates of survival and activation of oocytes vitrified at 0.5, 1, 2 and 4 h.p.a. were similar, but the parameters in other vitrified groups significantly decreased. Parthenogenetic development in vitrified 0.5, 1, 2 and 4 h.p.a. groups was also significantly higher than that in other vitrified groups. Moreover, the total cell numbers of blastocysts were similar among all groups.Porcine oocytes vitrified at 0.5-4 h h.p.a. showed acceptable survival and pronuclear formation, and a higher blastocyst yield could be obtained from these oocytes.

This investigation reports a novel room-temperature camphene-based freeze-casting method to prepare aligned and porous alumina ceramics. The ceramic/camphene/dispersant mixed slurries were solidified using a fast room-temperature cooling installation to form excessively overgrown camphene dendrites. The experimental results revealed that camphene-based freeze casting could lead to formation of an aligned and porous structure through room-temperature cooling in a copper die. As the ceramic solid loading increased from 8 to 20 vol.-%, the total porosity of the sintered porous alumina ceramics ranged from 80·5 to 67·5% and the compressive strength increased from 5·8 to 23·5 MPa. This freeze-cast processing is considered potentially useful in fabricating novel porous ceramics with special structure.

A variety of stressors including alcohol (EtOH) are known to induce collagen production and fibrotic diseases. Matrix metalloproteinases (MMP) play an important role in regulating fibrosis, but little is known regarding the relationship between EtOH and MMPs. In addition, the signaling cascades involved in this process have not been elucidated. We have identified the MMP Adamts1 as a target of EtOH regulation. To characterize the function of Adamts1, we examined EtOH-induced alterations in collagen I and elastin protein levels in C2C12 myocytes. Incubation of myocytes with 100 mM EtOH decreased elastin and increased collagen content, respectively, and these changes were associated with increased O-GLcNAc modification of Adamts1. Conversely, silencing of Adamts1 by siRNA blocked the adverse effects of EtOH on collagen and elastin levels. Similar results were obtained after treatment with a pharmacological inhibitor of MMP. Changes in collagen were due, at least in part, to a decreased interaction of Adamts1 with its endogenous inhibitor TIMP3. The AMPK inhibitor compound C blocked the EtOH-induced stimulation of collagen and O-GLcNAc Adamts1 protein. Changes in AMPK appear linked to FoxO1, since inhibition of FoxO1 blocked the effects of EtOH on AMPK phosphorylation and O-GLcNAc levels. These FoxO-dependent modifications were associated with an upregulation of the FoxO1 transcription target sestrin 3, as well as increased binding of sestrin 3 with AMPK. Collectively, these data indicate that EtOH regulates the collagen I and elastin content in an Adamts1-dependent manner in myocytes. Furthermore, Adamts1 appears to be controlled by the FoxO1-sestrin 3-AMPK signaling cascade.

In this paper, the ZTC4/B/C titanium matrix composite containing 0·2–0·5 wt-%B and 0·5–2 wt-%C was fabricated using melting–casting process. The microstructure and mechanical properties of as cast ZTC4/B/C Ti matrix composite were investigated. The results indicate that the microstructures of as cast ZTC4/B/C were consisted of lamellar α, β at grain boundary and second phases of bar-like TiB and spherical-like TiC. The elastic modulus of ZTC4/B with 0·5 wt-%B is 145 GPa, 30% higher than that of the matrix alloy. The ultimate tensile strength of ZTC4/B/C with 0·5 wt-%B and 0·5 wt-%C reached 1300 MPa, 25% higher than that of the matrix alloy.

Tensile tests were carried out at ambient temperature on one kind of near α titanium alloy named Ti-600 before and after being exposed at 600°C for 100 h. Fractography morphologies were investigated and fracture mechanisms were analysed. The results indicate that, compared with the sample without thermal exposure, the strength of the sample without oxidising layers increases by 1% or so, while the elongation decreases by about 20·4% for the alloy after thermal exposure. For the sample with oxidising layers, the ultimate strength decreases somewhat and the elongation decreases by 48·9%, indicating that the plasticity decreases abruptly during the thermal exposure process. For the solutioned plus aged samples, cracks originated from the centre of the fracture, and dimple-type fractures could be found. After long thermal exposure, for the samples without oxidising layers, hybrid fractures (both dimples and cleavage facets) can be seen. However, for the samples with oxidising layers, only cleavage fac...

Background Excessive alcohol (EtOH) consumption causes an imbalance in protein metabolism. EtOH impairs protein synthesis in C2C12 myoblasts via a FoxO1-AMPK-TSC2-mTORC1 pathway and also induces protein degradation. As the underlying regulatory signaling cascades for these processes are currently poorly defined, we tested the hypothesis that alcohol-induced autophagy is mediated via activation of the PIK3C3 complex that is regulated by FoxO1-AMPK. Methods C2C12 myoblasts were incubated with EtOH for various periods of time, and autophagy pathway-related proteins were assessed by Western blotting and immunoprecipitation. Expression of targeted genes was suppressed using electroporation of specific siRNAs and chemical inhibitors. Results Incubation of C2C12 myoblasts with 100 mM EtOH increased the autophagy markers LC3B-II and ATG7, whereas levels of SQSTM1/p62 decreased. The lysosomal inhibitor bafilomycin A1 caused a similar response, although there was no additive effect when combined with EtOH. EtOH altered ULK1 S555 and S757 phosphorylation in a time- and AMPK-dependent manner. The activation of AMPK and ULK1 was associated with increased BECN1 (S93, S14) and PIK3C3/VPS34 (S164) phosphorylation as well as increased total ATG14 and PIK3C3. These changes promoted formation of the ATG14-AMBRA1-BECN1-PIK3C3 proautophagy complex that is important in autophagosome formation. EtOH-induced changes were not associated with increased production of PtdIns3P, which may be due to enhanced PIK3C3 complex binding with 14-3-3θ. Reduction of AMPK using siRNA suppressed the stimulatory effect of EtOH on BECN1 S93, BECN1 S14, and PIK3C3 S164 phosphorylation in a time-dependent manner. Likewise, knockdown of AMPK or chemical inhibition of FoxO1 attenuated phosphorylation of ULK1 at both residues. Knockdown of ULK1 or BECN1 antagonized the effect of EtOH on LC3B-II, SQSTM1, and ATG7 protein expression. Conclusions EtOH-induced autophagy is mediated through changes in phosphorylation and interaction of various PIK3C3 complex components. This, in turn, is regulated either directly via FoxO1-AMPK or indirectly via the FoxO1-AMPK-ULK1 signaling cascade in a mTORC1-independent or mTORC1-dependent manner.

ObjectiveLimited studies have shown an association between the methyl-CpG-binding protein2 ( MeCp2) genetic polymorphisms and systemic lupus erythematosus (SLE) in different populations, but the results are inconclusive. In order to get a precise and systematic estimation, a meta-analysis was performed.MethodsA systematic literature search using English and Chinese databases (PubMed/Medline, Web of Knowledge, Wanfang Data (Chinese), etc.) for the eligible studies was performed. Based on heterogeneity among studies, random- or fixed-effects models were selected to analyze the risk of SLE associated with single-nucleotide polymorphisms (SNPs) of MeCP2 genetic polymorphisms.ResultsA significant increased risk of both SNPs of MeCP2 genetic variances associated with SLE was found. Analysis using a fixed-effects model found an increased risk of SLE with the A allele of rs2075596 (OR = 1.41, 95% CI: 1.34 to 1.49, p ConclusionsMutations of SNPs ( rs2075596, rs2239464) of MeCP2 showed increased risk of developing SLE. Large-scale multicenter epidemiological studies in selected populations with other risk factors are urgently required.

Nuclear receptor coactivator amplified in breast cancer-1 (AIB1), a new oncogenic coactivator, is commonly overexpressed and amplified in variety of human cancers. However, the expression of AIB1 in papillary thyroid carcinoma (PTC), the major histologic type of thyroid cancer, and its clinical significance are still unclear.AIB1 expression in PTC was examined by immunohistochemistry using tissue microarrays comprised of 90 primary PTC, 46 matched lymph node, and 20 normal thyroid tissue specimens in this study.In the normal thyroid specimens, AIB1 expression was either absent or at low levels. In contrast, AIB1 overexpression was detected in 50 of 83 (60.2 %) primary PTC specimens. Up-regulated AIB1 was evident in 39 of 46 (73.5 %) matched lymph nodes. Overexpression of AIB1 was observed more frequently in PTCs with lymph node metastasis [N1a/N1b, 39/46 (73.5 %)] versus PTCs without lymph node metastasis [N0, 14/34 (41.2 %)]. Furthermore, high-level AIB1 expression was only observed in the lymph node-positive specimens. Moreover, we found no correlation between AIB1 expression and ER expression in PTC tissues.Our findings suggest that overexpression of AIB1 may be a biomarker for tumorigenesis and progression of PTC and may play an important role in its acquisition of a metastatic phenotype.