Prognostic Molecular Biomarkers in Breast Cancer Lesions with Non-Mass Enhancement on MR.

Clustered ring enhancement (CRE) is a new lexicon for non-mass enhancement (NME) of breast MR in the 5th BIRADS, indicating a high suspicion of malignancy. We wonder if the presence of CRE correlates with expression of prognostic molecular biomarkers of breast cancer. A total of 58 breast lesions, which MRI reported with NME, were collected between July 2013 and December 2018. The patterns of enhancement including CRE were reviewed and the pathological results with expression of molecular biomarkers were collected. The association between MRI NME, pathological, and IHC stain findings were investigated under univariate analysis. A total of 58 breast lesions were pathologically proven to have breast cancer, comprising 31 lesions with CRE and 27 lesions without CRE on breast MRI. The expression of the estrogen receptor (ER) (p = 0.017) and the progesterone receptor (PR) (p = 0.017) was significantly lower in lesions with CRE as compared with those without CRE. The expression of Ki-67 (≥25%) was significantly higher in lesions with CRE (p = 0.046). The lesions with CRE had a lower expression ratio of ER (50.71 ± 45.39% vs. 74.26 ± 33.59%, p = 0.028). Our study indicated that lesions with CRE may possess different features from those without CRE in molecular expression, bearing a more aggressive behavior.

GRK2 expression and catalytic activity are essential for vasoconstrictor/ERK-stimulated arterial smooth muscle proliferation.

Prolonged vasoconstrictor signalling found in hypertension, increases arterial contraction, and alters vessel architecture by stimulating arterial smooth muscle cell (ASMC) growth, underpinning the development of re-stenosis lesions and vascular remodelling. Vasoconstrictors interact with their cognate G protein coupled receptors activating a variety of signalling pathways to promote smooth muscle proliferation. Here, angiotensin II (AngII) and endothelin 1 (ET1), but not UTP stimulates ASMC proliferation. Moreover, siRNA-mediated depletion of endogenous GRK2 expression, or GRK2 inhibitors, compound 101 or paroxetine, prevented AngII and ET1-promoted ASMC growth. Depletion of GRK2 expression or inhibition of GRK2 activity ablated the prolonged phase of AngII and ET-stimulated ERK signalling, while enhancing and prolonging UTP-stimulated ERK signalling. Increased GRK2 expression enhanced and prolonged AngII and ET1-stimulated ERK signalling, but suppressed UTP-stimulated ERK signalling. In ASMC prepared from 6-week-old WKY and SHR, AngII and ET1-stimulated proliferation rates were similar, however, in cultures prepared from 12-week-old rats AngII and ET1-stimulated growth was enhanced in SHR-derived ASMC, which was reversed following depletion of GRK2 expression. Furthermore, in ASMC cultures isolated from 6-week-old WKY and SHR rats, AngII and ET1-stimulated ERK signals were similar, while in cultures from 12-week-old rats ERK signals were both enhanced and prolonged in SHR-derived ASMC, and were reversed to those seen in age-matched WKY-derived ASMC following pre-treatment of SHR-derived ASMC with compound 101. These data indicate that the presence of GRK2 and its catalytic activity are essential to enable pro-proliferative vasoconstrictors to promote growth via recruitment and activation of the ERK signalling pathway in ASMC.

Targeting Inflammasome Activation in Viral Infection: A Therapeutic Solution?

Inflammasome activation is exclusively involved in sensing activation of innate immunity and inflammatory response during viral infection. Accumulating evidence suggests that the manipulation of inflammasome assembly or its interaction with viral proteins are critical factors in viral pathogenesis. Results from pilot clinical trials show encouraging results of NLRP3 inflammasome suppression in reducing mortality and morbidity in SARS-CoV-2-infected patients. In this article, we summarize the up-to-date understanding of inflammasomes, including NLRP3, AIM2, NLRP1, NLRP6, and NLRC4 in various viral infections, with particular focus on RNA viruses such as SARS-CoV-2, HIV, IAV, and Zika virus and DNA viruses such as herpes simplex virus 1. We also discuss the current achievement of the mechanisms involved in viral infection-induced inflammatory response, host defense, and possible therapeutic solutions.

Hyaline Vascular Type of Unicentric Castleman Disease in a Kidney with End-Stage Renal Disease: A Case Report of a Rare Entity at an Unusual Location and a Special Clinical Setting.

Castleman disease (CD) is an unusual heterogeneous lymphoproliferative disorder that has been classified based on either clinical presentation and disease course or histologic features. Clinically, CD is divided into a unicentric CD (UCD) type and multicentric CD (MCD) type according to the extent of lymph node region involvement and the absence or presence of systemic symptoms. Histologically, it can be categorized into hyaline vascular (HV) type, plasma cell (PC) type and mixed type. The majority of HV-type CD involves a solitary lymph node, and excision surgery is often curative. On the contrary, MCD is a progressive and often fatal disease with lymphadenopathy in multiple nodes, and systemic therapy is needed. Herein we report a unique case of HV-type CD presenting as a single renal mass in a patient with end-stage renal disease (ESRD). Despite the rarity, CD should be included in the differential diagnosis of solitary renal mass lesions. An accurate diagnosis is important to avoid unnecessarily risky or extensive operations.

Undifferentiated Carcinoma with Osteoclast-Like Giant Cells of the Common Bile Duct: A Case Report of a Rare Entity at an Unusual Location.

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare variant of carcinoma with unique radiological and pathological features. This unusual carcinoma has been reported in a variety of organs and pancreas is the most frequently involved anatomical site. UCOGC of pancreas attains a relatively indolent clinical behavior and should be distinguished from ordinary pancreatobiliary adenocarcinoma. This paper presents the first case of UCOGC involving the entire segment of common bile duct (CBD) and common hepatic duct (CHD) without extending to the pancreatic tissue. Getting familiar with its clinical, radiological and pathological characters can help establish accurate diagnosis despite the occurrence of an unusual location.

Colloid Carcinoma of the Pancreas with a Series of Radiological and Pathological Studies for Diagnosis: A Case Report.

Pancreatic colloid carcinoma is an uncommon and unique malignancy possessing a significantly more favorable prognosis than that of ordinary pancreatic ductal adenocarcinoma. Accurate diagnosis of this rare entity is thus important for leading the ensuing optimal treatment. Herein we report a case of colloid carcinoma of the pancreas with a series of imaging findings and pathologic assessments. Being familiar with these radio-pathological features makes early diagnosis possible prior to operation.

Distinctive patterns of marrow involvement by classic Hodgkin lymphoma are clues for diagnosis and subtyping.

Classic Hodgkin lymphoma (CHL) is a lymphoid neoplasm deriving from B cells in a rich inflammatory background. There are four histological subtypes with different epidemiological features. Bone marrow involvement by CHL is infrequent, and subtyping CHL from the bone marrow is not suggested as there might be discordant histopathology between the primary tumors and bone marrow specimens. In this study, we aimed to identify the histopathological features of bone marrow involved by CHL and tried to correlate these features with their subtypes. Among the 23 recruited cases, the frequencies of mixed cellularity (MC; 48%, 11/23) and nodular sclerosis (NS; 44%, 10/23) were similar. There were two patterns of marrow involvement: pattern A (fibrous), space-occupying lesions with alternating hypo- and hypercellular areas against a fibrotic background with dilated sinusoids and pattern B (histiocyte-rich), ill-defined granuloma-like lesions in which histiocytes merged with normal hematopoietic and inflammatory cells. Pattern A was more frequent in patients with CHL-NS than CHL-MC (100% vs. 18.2%; p < 0.001). Diagnostic Hodgkin cells and Reed-Sternberg (HRS) cells were identified in all cases, while HRS variant lacunar cells were occasionally discovered, particularly in the CHL-NS subtype (NS 100% vs. MC 9%; p < 0.001). The frequency of EBV association was higher in MC (64%) than that in NS (36%) subtype, but not statistically significant. Of the two patterns of marrow involvement, pattern A was more commonly associated with the NS subtype and less frequently associated with EBV. Recognizing the patterns of marrow involvement is important for diagnosis and may contribute to the subtyping of CHL.

Clinicopathologic Features of Lymphoproliferative Neoplasms Involving the Liver.

Background and Objectives: Primary hepatic lymphoproliferative neoplasms (PHL) are uncommon. This retrospective study is aimed to present the clinicopathological characteristics of PHL and compare to secondary hepatic lymphoproliferative neoplasms (SHL). Materials and Methods: Patients who were diagnosed with lymphoproliferative neoplasms involving the liver between January 2004 and December 2018 at a tertiary medical center in central Taiwan were included. The demographic and clinical data, radiological results and histopathological findings were reviewed and summarized. Results: We analyzed 36 patients comprising 6 PHL patients and 30 SHL patients. The median age at diagnosis tended to be younger in PHL than in SHL (59 vs. 63 years old, p = 0.349). Both entities had a small male predominance. The PHL patients tended to have higher levels of aspartate aminotransferase, alanine transaminase and serum albumin and lower levels of alkaline phosphatase, total bilirubin, γ-glutamyl transferase and lactate dehydrogenase compared with SHL, but there was no significant difference. Multiple mass lesions were the most common radiological finding in both groups. Diffuse large B-cell lymphoma was the predominant subtype in both groups (67% in PHL and 40% in SHL). The PHL patients had a longer median survival than the SHL patients (not reached vs. 3 months, p = 0.003). Conclusions: Although there was no significant difference between PHL and SHL in clinical, laboratory and radiological features, the SHL patients had very poor outcomes with a median survival time of 3 months. Effective therapies are urgently required for these patients.

Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study.

OBJECTIVE: To investigate the efficacy and safety of three H. erinaceus mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer's Disease (AD). METHODS: This study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period. RESULTS: After 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1-40 over the study period. Using diffusion tensor imaging, the mean apparent diffusion coefficient (ADC) values from the arcuate fasciculus region in the dominant hemisphere significantly increased in the placebo group while no significant difference was found in the EAHE group in comparison to their baselines. Moreover, ADC values from the parahippocampal cingulum region in the dominant hemisphere significantly decreased in the EAHE group whereas no significant difference was found in the placebo group when compared to their baselines. Lastly, except for four subjects who dropped out of the study due to abdominal discomfort, nausea, and skin rash, no other adverse events were reported. CONCLUSION: Three 350 mg/g EAHE capsules intervention for 49 weeks demonstrated higher CASI, MMSE, and IADL scores and achieved a better contrast sensitivity in patients with mild AD when compared to the placebo group, suggesting that EAHE is safe, well-tolerated, and may be important in achieving neurocognitive benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04065061.

Current research on liver regeneration: Pathogenesis and serum markers / 临床肝胆病杂志

Liver regeneration is an important response after liver injury and necrosis to maintain liver volume and function, with the involvement of various factors and signaling pathways. This process has three main stages, i.e., the initial stage of mitosis triggered by certain factors, the proliferation stage of promoting hepatocytes to enter the cell cycle, and the termination stage of promoting liver cells to reach a certain number and the recovery of liver mass. This article introduces various factors and multiple cellular signaling pathways that promote the differentiation of liver stem cells into liver cells to restore liver volume and function and summarizes the previous research findings of our group that alpha-fetoprotein is an important serum marker for liver regeneration after liver failure. The analysis shows that in-depth studies of the occurrence and clinical application of liver regeneration will help to improve the understanding of liver regeneration, better predict the prognosis of acute and chronic liver diseases, and provide new ideas and methods for the clinical diagnosis and treatment of various advanced liver diseases.

Psychoanalysis of 300 patients with chronic gastritis / 中华消化杂志

Objective:To analyze the difference of psychosocial characteristics in patients with chronic gastritis.Methods:From June to December 2018, a total of 300 patients with chronic gastritis visited Xijing Hospital were consecutively enrolled. The patients were divided into chronic non-atrophic gastritis (CNAG) group, chronic atrophic gastritis (CAG) group and CAG with intestinal metaplasia group, with 100 cases in each group. Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), living events scale (LES) and Eysenck personality questionnaire (EPQ) were used for evaluation and analysis. Chi square test, analysis of variance, nonparametric rank sum test and Kruskal Wallis H test were used for statistical analysis. Results:The incidences of anxiety of the CAG group and the CAG with intestinal metaplasia group were both significantly higher than that of the CNAG group (64.0%, 64/100; 53.0%, 53/100; and 34.0%, 34/100; respectively), and the differences were statistically significant ( χ2=0.007 and 0.001, both P<0.05). The incidence of depression of the CAG with intestinal metaplasia group was significantly higher than those of CNAG group and the CAG group (24.0%, 24/100; 15.0%, 15/100 and 13.0%, 13/100; respectively), and the differences were statistically significant ( χ2=0.108 and 0.045, both P<0.05). The negative event score of LES of CAG with intestinal metaplasia group was higher than those of CNAG group and CAG group (0 (0, 6.75), 0 (0, 1.00), 0 (0, 0.75) respectively), and the differences were statistically significant ( Z=-2.619 and -3.022, both P<0.05). The proportion of patients with LES score ≥20 points (high mental stress) of CNAG group, CAG group and CAG with intestinal metaplasia group gradually increased (8.0%, 8/100; 9.0%, 9/100 and 18.0%, 18/100; respectively), and the difference was statistically significant ( χ2=0.036, P<0.05). In male patients and patients under 50 years old, the incidence of depression and the proportions of patients with LES score ≥20 points of CAG with intestinal metaplasia group were higher than those of CNAG group (22.5%, 9/40 vs. 9.6%, 5/52; 47.5%, 19/40 vs. 16.2%, 11/68; 22.5%, 9/40 vs. 7.7%, 4/52; and 20.0%, 8/40 vs. 4.4%, 3/68), and the differences were statistically significant ( χ2=0.015, 0.001, 0.043 and 0.013, all P<0.05). The results of EPQ showed that the psychoticism, extraversion or introversion, stability and concealment of CNAG group and CAG with intestinal metaplasia group, were mostly normal (43.3 to 56.7), accounting for 62.0% (62/100) and 45.0% (45/100), 56.0% (56/100) and 44.0% (44/100), 54.0% (54/100) and 44.0% (44/100), 59.0% (59/100) and 45.0% (45/100), respectively. The percentage of patients with high score (>56.7) of etraversion or introversion and concealment in CAG group and the CAG with intestinal metaplasia group were higher than those in the CNAG group (48.0%, 48/100; 23.0%, 23/100; 4.0%, 4/100 and 46.0%, 46/100; 21.0%, 21/100 and 7.0%, 7/100, respectively), and the differences were statistically significant ( χ2=0.001, 0.001, 0.001 and 0.004, all P<0.01). Conclusions:Anxiety is associated with CAG and intestinal metaplasia, while depression is associated with intestinal metaplasia. In male patients and patients under 50 years old, depression, negative event and high psychiatric stress are more significantly related to intestinal metaplasia. The mental characteristics of extroversion, emotional instability, psychoticism and concealment are closely associated with CAG.

Ultrasound-Guided Core Needle Biopsies of Breast Invasive Carcinoma: When One Core is Sufficient for Pathologic Diagnosis and Assessment of Hormone Receptor and HER2 Status.

Ultrasound (US)-guided core needle biopsy is considered the gold standard procedure with regard to preoperative diagnosis of breast carcinomas. However, there is no clear standard for the number of cores considered to be sufficient for pathologic evaluation, including the expression of surface hormone markers and HER2 status. Images and pathologic slides demonstrating breast invasive carcinoma from a single institution were thus retrospectively reviewed over a 12 month period. The results indicated that one core is sufficient for the diagnosis of invasive carcinomas, along with a reliable assessment of hormone receptor and HER2 status in many cases. The option of applying additional cores is recommended for some cases.

gRASping the redox lever to modulate cancer cell fate signaling.

RAS proteins are critical regulators of signaling networks controlling diverse cellular functions such as cell proliferation and survival and its mutation are among the most powerful oncogenic drivers in human cancers. Despite intense efforts, direct RAS-targeting strategies remain elusive due to its "undruggable" nature. To that end, bulk of the research efforts has been directed towards targeting upstream and/or downstream of RAS signaling. However, the therapeutic efficacies of these treatments are limited in the long run due to the acquired drug resistance in RAS-driven cancers. Interestingly, recent studies have uncovered a potential role of RAS in redox-regulation as well as the interplay between ROS and RAS-associated signaling networks during process of cancer initiation and progression. More specifically, these studies provide ample evidence to implicate RAS as a redox-rheostat, manipulating ROS levels to provide a redox-milieu conducive for carcinogenesis. Importantly, the understanding of RAS-ROS interplay could provide us with novel targetable vulnerabilities for designing therapeutic strategies. In this review, we provide a brief summary of the advances in the field to illustrate the dual role of RAS in redox-regulation and its implications in RAS signaling outcomes and also emerging redox-based strategies to target RAS-driven cancers.

Breast reconstruction rate and profile in a Singapore patient population: a National University Hospital experience.

INTRODUCTION: Breast reconstruction is an integral part of breast cancer management with the aim of restoring a breast to its natural form. There is increasing awareness among women that it is a safe procedure and its benefits extend beyond aesthetics. Our aim was to establish the rate of breast reconstruction and provide an overview of the patients who underwent breast reconstruction at National University Hospital (NUH), Singapore. METHODS: We evaluated factors that impact a patient's decision to proceed with breast reconstruction, such as ethnicity, age, time and type of implant. We retrospectively reviewed the medical records of women who had breast cancer and underwent breast surgery at NUH between 2001 and 2010. RESULTS: The breast reconstruction rate in this study was 24.3%. There were 241 patients who underwent breast reconstruction surgeries (including delayed and immediate procedures) among 993 patients for whom mastectomies were done for breast cancer. Chinese patients were the largest ethnic group who underwent breast reconstruction after mastectomy (74.3%). Within a single ethnic patient group, Malay women had the largest proportion of women undergoing breast reconstruction (60.0%). The youngest woman in whom cancer was detected in our study was aged 20 years. Malay women showed the greatest preference for autologous tissue breast reconstruction (92.3%). The median age at cancer diagnosis of our cohort was 46 years. CONCLUSION: We noted increases in the age of patients undergoing breast reconstruction and the proportion of breast reconstruction cases over the ten-year study period.

Breast reconstruction rate and profile in a Singapore patient population: a National University Hospital experience

<p><b>INTRODUCTION</b>Breast reconstruction is an integral part of breast cancer management with the aim of restoring a breast to its natural form. There is increasing awareness among women that it is a safe procedure and its benefits extend beyond aesthetics. Our aim was to establish the rate of breast reconstruction and provide an overview of the patients who underwent breast reconstruction at National University Hospital (NUH), Singapore.</p><p><b>METHODS</b>We evaluated factors that impact a patient's decision to proceed with breast reconstruction, such as ethnicity, age, time and type of implant. We retrospectively reviewed the medical records of women who had breast cancer and underwent breast surgery at NUH between 2001 and 2010.</p><p><b>RESULTS</b>The breast reconstruction rate in this study was 24.3%. There were 241 patients who underwent breast reconstruction surgeries (including delayed and immediate procedures) among 993 patients for whom mastectomies were done for breast cancer. Chinese patients were the largest ethnic group who underwent breast reconstruction after mastectomy (74.3%). Within a single ethnic patient group, Malay women had the largest proportion of women undergoing breast reconstruction (60.0%). The youngest woman in whom cancer was detected in our study was aged 20 years. Malay women showed the greatest preference for autologous tissue breast reconstruction (92.3%). The median age at cancer diagnosis of our cohort was 46 years.</p><p><b>CONCLUSION</b>We noted increases in the age of patients undergoing breast reconstruction and the proportion of breast reconstruction cases over the ten-year study period.</p>

SDF-1 and CXCR4 play an important role in adult SVZ lineage cell proliferation and differentiation.

Evidence has shown that stromal cell-derived factor (SDF-1/CXCL12) plays an important role in maintaining adult neural progenitor cells (NPCs). SDF-1 is also known to enhance recovery by recruiting NPCs to damaged regions and recent studies have revealed that SDF-1α exhibits pleiotropism, thereby differentially affecting NPC subpopulations. In this study, we investigated the role of SDF-1 in in vitro NPC self-renewal, proliferation and differentiation, following treatment with different concentrations of SDF-1 or a CXCR4 antagonist, AMD3100. We observed that AMD3100 inhibited the formation of primary neurospheres. However, SDF-1 and AMD3100 exhibited no effect on proliferation upon inclusion of growth factors in the media. Following growth factor withdrawal, AMD3100 and SDF-1 treatment resulted in differential effects on NPC proliferation. SDF-1, at a concentration of 500ng/ml, resulted in an increase in the relative proportion of oligodendrocytes following growth factor withdrawal-induced differentiation. Using CXCR4 knockout mice, we observed that SDF-1 affected NPC proliferation in the sub-ventricular zone (SVZ). We also investigated the occurrence of differential CXCR4 expression at different stages during lineage progression. These results clearly indicate that signaling interactions between SDF-1 and CXCR4 play an important role in adult SVZ lineage cell proliferation and differentiation.