Search

Ferroptosis is a novel form of programmed cell death triggered by iron‐dependent lipid peroxidation and has been associated with various diseases, including cancer. Erastin, an inhibitor of system Xc‐, which plays a critical role in regulating ferroptosis, has been identified as an inducer of ferroptosis in cancer cells. In this study, we investigated the impact of butyrate, a short‐chain fatty acid produced by gut microbiota, on erastin‐induced ferroptosis in lung cancer cells. Our results demonstrated that butyrate significantly enhanced erastin‐induced ferroptosis in lung cancer cells, as evidenced by increased lipid peroxidation and reduced expression of glutathione peroxidase 4 (GPX4). Mechanistically, we found that butyrate modulated the pathway involving activating transcription factor 3 (ATF3) and solute carrier family 7 member 11 (SLC7A11), leading to enhanced erastin‐induced ferroptosis. Furthermore, partial reversal of the effect of butyrate on ferroptosis was observed upon knockdown of ATF3 or SLC7A11. Collectively, our findings indicate that butyrate enhances erastin‐induced ferroptosis in lung cancer cells by modulating the ATF3/SLC7A11 pathway, suggesting its potential as a therapeutic agent for cancer treatment. [ABSTRACT FROM AUTHOR]

To solve the problems of voltage violation and fast voltage fluctuation caused by photovoltaic (PV) grid connections in distribution networks, a two‐stage coordinated voltage control strategy for PV inverters with multimode coordinated operation in distribution networks (DNs) is proposed. It is based on the characteristics of PV inverters that can be regulated rapidly and continuously. First, the voltage control process is divided into two control stages according to the voltage change rate, and the corresponding voltage control models are established. Then, the operating modes of PV inverters are classified into three modes: economic prevention, economic control, and efficient control. Different operating modes are used to adapt to the two‐stage voltage control. Finally, a voltage fast control solution algorithm is proposed, which considers adaptive time delays and combines local measurement, prediction, and communication information to update control commands. The effectiveness and feasibility of the proposed voltage control strategy were demonstrated through simulation tests on a real 10‐kV line with a high PV penetration rate in the Anhui province of China. The results show that the proposed strategy can prevent voltage violation and sudden changes and can smooth out voltage fluctuation. [ABSTRACT FROM AUTHOR]

Aims: In 2017, a subset of cellular variants of myofibroma and myopericytoma with a smooth muscle‐like immunophenotype and harbouring recurrent SRF::RELA gene fusions was reported. Although the anatomical distribution was found to be quite broad, no tumours with these gene fusions in the female reproductive system have been illustrated to date. Methods and results: Herein, we report the histological and immunophenotypical features of three uterine tumours with SRF::RELA gene fusions. Microscopically, all three tumours were composed of cellular oval to spindle cells arranged in intersecting fascicles with variable amounts of collagen and a rich capillary network. Mitotic figures were scant. Regarding immunohistochemistry, diffuse staining for desmin, oestrogen receptor and progesterone receptor was observed in all three cases. The first case exhibited focal staining for h‐caldesmon, whereas the latter two cases had diffuse staining. Furthermore, SRF::RELA rearrangement was observed in all three cases by using next‐generation sequencing (NGS). Follow‐up, ranging from 11 to 15 months, was available for these three patients, all of whom were well without evidence of disease. Conclusions: In conclusion, we reported a special group of uterine neoplasms with myogenic differentiation harbouring SRF::RELA rearrangement. Although the follow‐up time was limited, morphological characteristics and other studies with follow‐up data supported that this type of uterine neoplasm appeared to behave in a benign manner. Further studies with longer follow‐up are needed to clarify the biological nature of this particular type of uterine tumour. [ABSTRACT FROM AUTHOR]

Clear cell carcinoma (CCC) of the cervix (cCCC) is a rare and aggressive type of human papillomavirus (HPV)‐negative cervical cancer with limited effective treatment options for recurrent or metastatic disease. Historically, CCCs of the lower genital tract were associated with in utero diethylstilbestrol exposure; however, the genetic landscape of sporadic cCCCs remains unknown. Here we sought to define the molecular underpinning of cCCCs. Using a combination of whole‐exome, targeted capture, and RNA‐sequencing, we identified pathogenic genetic alterations in the Hippo signaling pathway in 50% (10/20) of cCCCs, including recurrent WWTR1 S89W somatic mutations in 40% (4/10) of the cases harboring mutations in the Hippo pathway. Irrespective of the presence or absence of Hippo pathway genetic alterations, however, all primary cCCCs analyzed in this study (n = 20) harbored features of Hippo pathway deregulation at the transcriptomic and protein levels. In vitro functional analysis revealed that expression of the WWTR1 S89W mutation leads to reduced binding of TAZ to 14‐3‐3, promoting constitutive nuclear translocation of TAZ and Hippo pathway repression. WWTR1 S89W expression was found to lead to acquisition of oncogenic behavior, including increased proliferation, migration, and colony formation in vitro as well as increased tumorigenesis in vivo, which could be reversed by targeted inhibition of the TAZ/YAP1 complex with verteporfin. Finally, xenografts expressing WWTR1 S89W displayed a shift in tumor phenotype, becoming more infiltrative as well as less differentiated, and were found to be composed of cells with conspicuous cytoplasmic clearing as compared to controls. Our results demonstrate that Hippo pathway alterations are likely drivers of cCCCs and likely contribute to the clear cell phenotype. Therapies targeting this pathway may constitute a new class of treatment for these rare, aggressive tumors. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

In order to reduce the impact of renewable energy output and load fluctuations and improve the flexibility of the integrated energy system (IES), it is necessary to further promote user participation in integrated demand response (IDR). Therefore, this paper constructs a hierarchical framework that enables the transaction of IDR resources among users by combining the information interaction network established by blockchain and the energy management network established by energy management system. This paper also analyses the comfort of users, the cost of energy purchase by users and the cost of energy use by load aggregators, and then develops a two‐layer optimization model. The results of the simulation show that the model and trading framework constructed in this paper can realize the trading of IDR resources among users, which effectively promotes the participation of users in IDR, reduces the cost of users and load aggregators, reduces the loss of IDR resources, enables more effective integration of dispersed IDR resources and improves the flexibility of IES. [ABSTRACT FROM AUTHOR]

With the rapid development of carbon trading market, the volatility trend of carbon emission trading price (CETP) becomes one of the factors that cannot be ignored in energy system planning. Based on this, this paper proposes a multi‐objective expansion planning model for park‐level integrated energy system (PIES) that takes into account the volatility trend of CETP. First, the influencing factors of CETP prediction are filtered and downscaled, and a kernel extreme learning machine (KELM) model based on the improved multi‐objective grey wolf algorithm optimizer (IMOGWO) is used for probabilistic interval prediction of CETP. Next, the operational characteristics of each carbon emission device are analysed and a model for calculating the cost of carbon trading is proposed. Then, a two‐layer PIES planning model is developed with the objective of minimizing the annualized system cost and carbon emissions during the expansion planning cycle, the upper‐layer model is a planning model for solving equipment expansion scenarios, and the lower‐layer model is an operation model for calculating typical operation schemes. Finally, the simulation effect of the prediction model is verified by the European carbon trading data, and the planning schemes are compared and analysed to prove the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Time‐of‐use (TOU) electricity prices are implemented based on the response characteristics of users. TOU prices guide the electricity consumption behaviour of users and make them actively respond to peak shaving and valley filling. In this paper, the conventional psychology response model of consumers is improved based on the history data of customer response to the TOU price. The paper defines four types of response load curves and proposes the response reliability indices. Additionally, it establishes the probability models of customer response. According to the characteristics of customer response, the sensitivity analysis of influencing factors and the risk analysis of customers are carried out according to the probability model of response. For instance, risk and characteristics analyses of the customer response were performed using the load data of residential areas in Nanjing city. The results indicate that the probability distribution of the customer response is approximate to the trapezoid distribution. The sequence of sensitivity coefficients of customer response factors is as follows: customer income, type of customer, and electrical equipment. The proposed method provides a scientific basis for electricity price implementers to accurately grasp the response behaviour of the user and establish a reasonable demand response strategy. [ABSTRACT FROM AUTHOR]

Previous genotyping‐based assays have identified non‐coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of coding variants within all IL family genes in leprosy was still limited. To obtain the full mutation spectrum of all ILs in leprosy, we performed a targeted deep sequencing of coding regions of 58 ILs genes in 798 leprosy patients (age 56.2 ± 14.4; female 31.5%) and 990 healthy controls (age 38.1 ± 14.0; female 44.3%) from Yunnan, Southwest China. mRNA expression alterations of ILs in leprosy skin lesions or in response to M. leprae treatment were estimated by using publicly available expression datasets. Two coding variants in IL27 (rs17855750, p.S59A, p = 4.02 × 10−8, odds ratio [OR] = 1.748) and IL1RN (rs45507693, p.A106T, p = 1.45 × 10−5, OR = 3.629) were significantly associated with leprosy risk. mRNA levels of IL27 and IL1RN were upregulated in whole blood cells after M. leprae stimulation. These data showed that IL27 and IL1RN are leprosy risk genes. Further functional study is required for characterizing the exact role of ILs in leprosy. [ABSTRACT FROM AUTHOR]

This study aimed to translate the Perspectives on Caring for Older Patients scale into Chinese, both the full and the shortened versions, and test its psychometric properties among Chinese nursing students. In this methodological research, the scale were translated and administered to 307 nursing students recruited from two universities in mainland China. The psychometric testing mainly included internal consistency reliability using Cronbachʼs alphas, 2‐week test–retest reliability using the intraclass correlation coefficient, convergent validity with Koganʼs Attitude toward Older People scale, and factorial validity using exploratory factor analysis. Cronbachʼs alphas for the full and the shortened version scales were 0.77 and 0.75, respectively. The intraclass correlation coefficient values of both versions exceeded 0.70 and their scores were moderately correlated with the Koganʼs Attitude toward Older People scaleʼs scores. While exploratory factor analyses revealed a six‐factor structure for the full version with factor loadings of five items below 0.3, the shortened version identified two factors with all factor loadings above 0.3. This study concluded that the psychometric properties of the full version scale were adequate and similar to those of the shortened version except for factorial validity. [ABSTRACT FROM AUTHOR]

This study presents an analysis method of harmonic interaction characteristics between direct‐drive wind turbines (DDWTs) based on αβ coordinates and the relative gain array (RGA). First, considering the digital delay of inverters, the capacitive current feedback active damping is applied to suppress the resonance of LCL filter, and the output current of DDWT is regulated by quasi‐proportional resonant controller in the αβ coordinates and then combined with the topology of the direct‐drive wind farm (DDWF), the transfer function matrix of the DDWF is established. Second, based on the RGA principle, the relationship between parameters and harmonic interaction characteristics is quantitatively analysed. The results show that with the proportional coefficient increasing, the degree of negative interaction between DDWTs is strengthened, which increases the harmonic content in the negative interaction frequency band. However, the increase of resonance coefficient and number of DDWTs will weaken the degree of negative interaction. In addition, with the increase of capacitive current feedback coefficient and grid inductance, the interaction frequency gradually decreases. Finally, the DDWF model is built both on Matlab/Simulink and StarSim + PXI hardware‐in‐the‐loop platform to verify the analytical results. The harmonic interaction characteristics can be used to guide the parameter design of DDWTs, so as to optimise power quality of the wind farm. [ABSTRACT FROM AUTHOR]

Background: Defects in DNA damage repair (DDR) system may lead to genomic instability and manifest as increased immunogenicity. DDR deficiency is prevalent in ovarian cancer (OvCa); however, the association of DDR mutation with immune profiles in OvCa remains largely unknown. This knowledge will provide an essential basis to the rational design of biomarker‐guided immune combination therapy of OvCa in the future. Methods: Whole‐exome sequencing data of 587 OvCa from The Cancer Genome Atlas (TCGA) were used to determine the expression profiles of 47 immune‐related genes and the abundance of tumor‐infiltrating immune cells. A Chinese OvCa cohort (n = 220) tested by next‐generation sequencing (NGS) was used to validate the association between DDR status and tumor mutation burden (TMB). Results: A total of 19.3% in TCGA cohort and 25.9% in Chinese cohort harbored at least one DDR somatic mutation. DDR deficiency exhibited a distinct immune profile with significant higher expression levels of PTPRCAP, CCL5, IFI16, LAG3, IL15RA, and GBP1 in OvCa in the TCGA cohort. Different DDR pathway deficiency displayed various immune profiles. Increased levels of Th1 cells, TMB, and neoantigen were also observed in DDR‐deficient tumors. Conclusions: DDR deficiency was associated with specific immune signatures in OvCa. Our findings emphasize the urgent need for biomarker‐guided rational immune combination therapy to maximize the OvCa patients who could benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

As inherited genetic alterations are important etiological factors causing endometrial cancer (EC), our study aimed to outline the ethnic‐related prevalence and the associated clinical and biological characteristics of germline mutations in cancer predisposition genes in Chinese EC patients. One hundred ninety‐eight Chinese EC patients were screened for germline mutations in a panel of cancer susceptibility genes using next‐generation sequencing combined with multiplex ligation‐dependent probe amplification. First, we found that among patients under 50 years of age, 26% (18/69) carried germline genetic mutations, all involving mismatch repair (MMR) genes except for one mutation affecting BRCA1. Second, when we focused on Lynch syndrome (LS) with additional selected patients, 45 were identified to carry pathogenic mutations in MMR genes, with a higher frequency found in MSH2 and MSH6. We found that age at onset, personal and familial history together with immunohistochemical assay results were the most useful criteria for the diagnosis of LS although limitations in routine practice and the sensitivity and specificity of each parameter should be taken into account. One pathogenic mutation in the PALB2 gene was detected in a patient with no breast cancer in her family. Interestingly, we identified a family carrying pathogenic variant in both PMS2 and BRCA1 genes with distinct clinical phenotypes. Multigene panel testing should be recommended to patients based on their clinical information and tumor phenotype. Our study also showed the genetic complexity in EC, which requires further investigations. What's new? Endometrial cancer incidence is increasing in China, presumably owing in part to greater exposure to environmental risk factors such as obesity and hormone therapy. The degree to which hereditary factors influence endometrial cancer burden in Asian populations remains uncertain. Here, screening for germline mutations shows that more than one‐fourth of young Asian endometrial cancer patients carry variants in cancer predisposition genes, primarily mismatch repair (MMR) genes. Most variants affected MMR genes associated with Lynch syndrome. Multigene panel testing further led to the identification of rare mutations in patients with no apparent family history, highlighting a clinical need for mutational screening. [ABSTRACT FROM AUTHOR]

Aims: The protein expression of programmed death‐ligand 1 (PD‐L1) has been recognised as being a biomarker for poor prognosis in diffuse large B‐cell lymphoma (DLBCL). The aims of this study were to determine PD‐L1 DNA status and mRNA status, and to explore whether they contribute to protein expression and their clinicopathological correlation in DLBCL. Methods and results: In this study, we used fluorescence in‐situ hybridisation, RNA in‐situ hybridisation and immunohistochemistry to determine PD‐L1 status at three different levels in 287 DLBCL samples with follow‐up. Their correlation and clinical pathological relevance were also analysed. Our results showed that 1.7% (3/175) of patients had PD‐L1 DNA amplification, 19.9% (57/287) had high PD‐L1 mRNA expression, and 11.8% (34/287) had high PD‐L1 protein expression. Both mRNA and protein expression of PD‐L1 were significantly higher in non‐germinal centre B‐cell‐like (GCB) DLBCL than in GCB DLBCL (P < 0.05). In addition, the patients with high PD‐L1 mRNA or high PD‐L1 protein expression but no PD‐L1 DNA amplification had significantly poorer overall survival (OS) than those with low PD‐L1 expression (P < 0.05). Furthermore, we found that PD‐L1 mRNA and PD‐L1 protein expression were highly correlated (P = 0.012), which was observed in all three samples with DNA amplification. Conclusions: PD‐L1 DNA amplification is a rare event, PD‐L1 mRNA is the main contributor to the high PD‐L1 protein expression, and the latter two will serve as important biomarkers for predicting the prognosis of DLBCL patients and selecting them for immunotherapy. [ABSTRACT FROM AUTHOR]

Aims: Pure mucinous carcinoma (PMC) of the breast is a low‐grade cancer. In this study, we aimed to elucidate the prognostic significance of micropapillary structures in breast PMC. Methods and results: Seventy‐five patients with breast PMC were recruited. All haematoxylin and eosin (H&)‐stained slides were reviewed, and clinicopathological features including age, tumour size, growth pattern, nuclear grade, histological grade, lymph node (LN) status, immunohistochemistry (IHC) staining of hormone receptor, human epidermal growth factor receptor 2 (HER2) expression and Ki‐67 proliferation index were analysed. Fluorescence in‐situ hybridisation (FISH) was used to verify the amplification of the HER2 gene in IHC 2+ cases. Seventy‐one cases of PMC were followed‐up from 18 to 110 months (median = 68 months). All PMC patients were female, aged 31–83 years (median = 57 years). All PMCs were nuclear grades 1 or 2. Oestrogen receptor was positive in all cases (100%) and progesterone receptor was positive in 68 cases (90.7%). There was no 3+ staining or gene amplification of HER2. Four patients had axillary LN metastasis (5.7%). Micropapillae were observed in 60 cases (80%) with varied percentages, and divided into five groups: 0%, <20%, 20–49%, 50–89% and ≥90%, with 15 (20%), 15 (20%), 17 (22.7%), 17 (22.7%) and 11 (14.7%) cases in each. Follow‐up results showed that neither recurrence nor distant metastasis occurred in all PMCs. Statistical analysis revealed that only larger tumour size was correlated significantly with LN metastasis (P < 0.05). Conclusions: The presence of nuclear grades 1 or 2 micropapillae, irrespective of the percentage, had no significant relationship with LN metastasis and patients' survival of PMC. [ABSTRACT FROM AUTHOR]

Abstract: Some histone deacetylases (HDACs) promote tumor cell growth and pan‐ or selective HDAC inhibitors are active in some cancers; however, the pivotal HDAC enzyme and its functions in human diffuse large B‐cell lymphoma (DLBCL) remain largely unknown. Using NanoString nCounter assays, we profiled HDAC mRNA expression and identified HDAC6 as an upregulated HDAC family member in DLBCL tissue samples. We then found that HDAC6 plays an oncogenic role in DLBCL, as evidenced by its promotion of cell proliferation in vitro and tumor xenograft growth in vivo. Mechanistically, the interaction between HDAC6 and HR23B downregulated HR23B expression, thereby reducing the levels of casitas B‐lineage lymphoma (c‐Cbl), an E3 ubiquitin ligase for hepatocyte growth factor receptor (MET), which resulted in the inhibition of MET ubiquitination‐dependent degradation. In addition, enhanced HDAC6 expression and decreased HR23B expression were correlated with poor overall survival rates among patients with DLBCL. Taken together, these results establish an HDAC6–HR23B–MET axis and indicate that HDAC6 is a potent promoter of lymphomagenesis in DLBCL. Thus, a therapeutic strategy based on HDAC6 inhibitors in combination with MET inhibitors is promising. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Profiling the spatial‐temporal expression pattern and characterizing the regulatory networks of brain tissues are vital for understanding the pathophysiology of Alzheimer's disease (AD). Methods: We performed a systematic integrated analysis of expression profiles of AD‐affected brain tissues (684 AD and 562 controls). A network‐based convergent functional genomic approach was used to prioritize possible regulator genes during AD development, followed by functional characterization. Results: We generated a complete list of differentially expressed genes and hub genes of the transcriptomic network in AD brain and constructed a Web server (www.alzdata.org) for public access. Seventeen hub genes active at the early stages, especially YAP1, were recognized as upstream regulators of the AD network. Cellular assays proved that early alteration of YAP1 could promote AD by influencing the whole transcriptional network. Discussion: Early expression disturbance of hub genes is an important feature of AD development, and interfering with this process may reverse the disease progression. [ABSTRACT FROM AUTHOR]

Aims: To analyse the clinicopathological, immunohistochemical and β-catenin (CTNNB1) mutation characteristics of six cases of microcystic stromal tumour of the ovary (MCST). Methods and results: Six Chinese patients with MCST who ranged in age from 29 to 69 years (mean 50 years) were included in the study. Five patients were detected with a pelvic mass during routine health examinations and one patient presented initially with opsomenorrhoea. All tumours involved the left ovary, with solid-cystic cut surface in five cases and cystic cut surface in one case. Microscopically, microcysts, solid nests and hyaline degenerated fibrous stroma were variably mixed. Immunohistochemically, the tumour cells in all cases were diffusely positive for CD10, vimentin and WT-1 and negative for α-inhibin and calretinin. β-catenin expression was observed in both the nucleus and the cytoplasm in five cases and only in the cytoplasm in one case. The results of CTNNB1 mutation analysis revealed four missense point mutations in four cases, which were c.97T>C, c.101G>A, c.110C>G and c.122C>T. Conclusions: MCST shows a unique morphology with characteristic immunophenotype. β-catenin expression in the nucleus and b-catenin mutations were identified in the majority of cases, which suggests that the Wnt/β-catenin pathway may play a crucial role in the tumorigenesis of MCST. [ABSTRACT FROM AUTHOR]

The recent dramatic increase in breast cancer incidence across China with progressive urbanization and economic development has signaled the urgent need for molecular and clinical detailing of breast cancer in the Chinese population. Our analyses of a unique transethnic collection of breast cancer frozen specimens from Shanghai Fudan Cancer Center ( Chinese Han) profiled simultaneously with an analogous Caucasian Italian series revealed consistent transcriptomic data lacking in batch effects. The prevalence of Luminal A subtype was significantly lower in Chinese series, impacting the overall prevalence of estrogen receptor ( ER)-positive disease in a large cohort of Chinese/ Caucasian patients. Unsupervised and supervised comparison of gene and microRNA ( miRNA) profiles of Chinese and Caucasian samples revealed extensive similarity in the comprehensive taxonomy of transcriptional elements regulating breast cancer biology. Partition of gene expression data using gene lists relevant to breast cancer as 'intrinsic' and 'extracellular matrix' genes identified Chinese and Caucasian subgroups with equivalent global gene and miRNA profiles. These findings indicate that in the Chinese and Caucasian groups, breast neoplasia and the surrounding stromal characteristics undergo the same differentiation and molecular processes. Transcriptional similarity across transethnic cohorts may simplify translational medicine approaches and clinical management of breast cancer patients worldwide. [ABSTRACT FROM AUTHOR]

Purpose To assess the value of maximal extramural depth (EMD) of T3 tumor spread on MRI as a potential noninvasive imaging biomarker of tumor aggressiveness in rectal cancer, by analyzing the relationship between tumoral EMD values and clinical or histological prognostic parameters. In addition, we try to investigate the relationship between EMD and apparent diffusion coefficient (ADC) values. Materials and Methods Ninety rectal cancer patients who underwent primary MRI staging and diffusion weighted imaging (DWI) as T3 tumor were included. Tumor EMD was measured, and the EMD values of the subgroups based on pretreatment CEA, CA19-9 levels, N stage, and histological parameters were compared. The correlation between EMD and ADC values was compared. Results Interobserver agreement of confidence levels for observers 1 and 2 was good for cN stage (k = 0.678) and EMD measurement(k = 0.612) and was excellent for ADC measurement (k = 0.880). Tumor EMDs differ between CEA <5 ng/mL versus ≥ 5 ng/mL ( P = 0.013), CA19-9 < 27 U/mL versus ≥ 27 U/mL ( P = 0.012), the groups of cN0 versus cN+ cancers ( P = 0.049), and between the several groups of histological differentiation grades ( P = 0.033). There was no significant difference in EMDs between the various groups of vessel carcinoma embolus and neural invasion. A significant negative correlation (r = −0.581; P = 0.001) between ADC and EMD values was found. Conclusion Significant correlations were found between EMD values and CEA, CA19-9 level, differentiation grade and ADC value. As been found, higher EMD values were associated with a more aggressive tumor profile and, therefore, EMD has the potential to become an imaging biomarker of tumor aggressiveness indicator. J. Magn. Reson. Imaging 2014;40:738-744. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Matrix-producing carcinoma (MPC) of the breast is an extremely rare variant of metaplastic carcinoma. The aim of this study was to evaluate the clinicopathological features and immunohistochemical expression profile of this rare tumor in Chinese population. Thirteen cases of MPC were evaluated using morphology observation and immunohistochemistry. All tumors had invasive carcinoma with an abrupt transition to chondromyxoid matrix without an intervening spindle cell sarcomatoid component. The distribution of tumor cells was diffuse in eight cases and peripheral in five cases. Matrix distribution was diffuse or multifocal. Necrosis was present in 11 cases. An overt invasive ductal carcinoma was observed in 11 cases and the other two tumors were consistent with MPC arising in microglandular adenosis. Ten of 13 cases were triple negative (ER-, PR-, Her2/neu-). Eight of 10 triple negative cases were cytokeratin 5/6, cytokeratin 14 or epidermal growth factor receptor positive, consistent with the basal-like phenotype. S-100 protein was positive in all cases. At the time of initial diagnosis, one of 13 patients had lung metastasis and axillary lymph nodes metastasis. Follow-up time ranged from 6 to 30 months. All patients remained alive. One patient developed a soft tissue metastasis 24 months after surgery. [ABSTRACT FROM AUTHOR]

Objective Women of childbearing age are more likely than men to experience temporomandibular disorders, with pain as the main symptom. Temporomandibular joint (TMJ) inflammation is believed to be a major reason for TMJ pain. Whether sex hormones are involved in the sexual dimorphism of TMJ inflammation and pain remains to be elucidated. The aim of this study was to examine whether estrogen affects TMJ inflammation and pain via the NF-κB pathway. Methods Female rats were divided into 6 groups: the control group, the sham-ovariectomized group, and 4 groups of ovariectomized rats treated with 17β-estradiol at a dosage of 0 μg/day, 20 μg/day, 80 μg/day, and 200 μg/day, respectively, for 10 days and then injected intraarticularly with Freund's complete adjuvant to induce TMJ inflammation. The behavior-related and histologic effects of 17β-estradiol were evaluated 24 hours after the induction of TMJ inflammation. NF-κB activity in the synovial membrane was examined by electrophoretic mobility shift assay. The expression of the NF-κB target genes tumor necrosis factor α, interleukin-1β (IL-1β), IL-6, cyclooxygenase 2, and inducible nitric oxide synthase in the synovial membrane was examined by real-time polymerase chain reaction. Results Treatment with estradiol potentiated TMJ inflammation in a dose-dependent manner and also exacerbated the inflammation-induced decrease in food intake. Correspondingly, estradiol potentiated the DNA-binding activity of NF-κB and the transcription of its target genes in the synovial membrane. Furthermore, the estrogen receptor antagonist ICI 182780 or the NF-κB inhibitor pyrrolidine dithiocarbamate partially blocked the effects of estradiol on TMJ inflammation and pain and the NF-κB pathway. Conclusion These results suggest that estradiol aggravates TMJ inflammation through the NF-κB pathway, leading to the induction of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]