A Frequent Diagnostic Pitfall: Dermatological Clinical Features and Pathological Results in Diagnosing Pagetoid Squamous Cell Carcinoma in situ (Case Series)

Sheng-Kai Wang,1 Jia-Wei Cai,2 Yu Zhang,3 Ya-Jing Lin,4 Yi-Hui Yang2 1Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, People’s Republic of China; 2Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 3Department of Pathology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Clinical Laboratory, the First People’s Hospital of Wenling, Affiliated to Wenzhou Medical University, Taizhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yi-Hui Yang, Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No. 365, Renmin East Road, Jinhua, 321000, People’s Republic of China, Tel/Fax +86 139 5848 5323, Email [email protected]: Squamous cell carcinoma (SCC) in situ can occur on any skin or mucus surface and is more commonly found in elderly patients on areas of skin that have been sunburnt. Most previous case reports are from dermatologists, with few published reports from pathologists. In this study, three patients underwent pathological routine and auxiliary immunohistochemical (IHC) examination and were ultimately diagnosed with pagetoid SCC in situ – a different diagnosis from the initial clinical assessment. All three patients received a complete resection of the skin mass. After follow-up, as of June 2023, the patients had no tumour recurrence or metastasis. Pagetoid SCC in situ is a particular type of SCC in situ that has no specific features in clinical manifestations, gross diagnosis or histopathological sections. The final diagnosis depends on IHC staining. Pagetoid SCC in situ expresses EMA, CK5/6 and p63 but not CEA, CK8 or S-100, which are expressed in extramammary Paget’s disease. Pagetoid SCC in situ is usually only locally invasive, and the main treatment is complete surgical resection. The prognosis is related to human papillomavirus infection, surgical margin closure, disease location, tumour thickness and other factors.Keywords: pagetoid, pagetoid squamous cell carcinoma in sit

Clustering of Multilevel Factors Among Children and Adolescents:Associations With Health-Related Physical Fitness

BACKGROUND: To identify the clustering characteristics of individual-, family-, and school-level factors, and examine their associations with health-related physical fitness. METHODS: A total of 145,893 Chinese children and adolescents aged 9-18 years participated in this cross-sectional study. The 2-step cluster analysis was conducted to identify clusters among individual-, family-, and school-level factors. Physical fitness indicator was calculated through sex- and age-specific z scores of forced vital capacity, standing long jump, sit-and-reach flexibility, body muscle strength, endurance running, and body mass index. RESULTS: Three, 3, and 5 clusters were automatically identified at individual, family, and school levels, respectively. Students with low physical fitness indicator were more likely to be in the "longest sedentary time and skipping breakfast" cluster (odds ratio [OR] = 1.18; 95% confidence interval [CI], 1.12-1.24), and "physical inactivity and insufficient protein consumption" cluster (OR = 1.07; 95% CI, 1.02-1.12) at individual level, the "single children and high parental education level" cluster (OR = 1.15; 95% CI, 1.10-1.21), and "no physical activity support and preference" cluster (OR = 1.30; 95% CI, 1.25-1.36) at family level, and the "physical education occupied" cluster (OR = 1.06; 95% CI, 1.01-1.11), and "insufficient physical education frequency" cluster (OR = 1.16; 95% CI, 1.08-1.24) at school level. Girls were more vulnerable to individual- and school-level clusters, while boys were more susceptible to family clusters; the younger students were more sensitive to school clusters, and the older students were more susceptible to family clusters (P-interaction &lt; .05). CONCLUSIONS: This study confirmed different clusters at multilevel factors and proved their associations with health-related physical fitness, thus providing new perspective for developing targeted interventions.</p

Clustering of Multilevel Factors Among Children and Adolescents:Associations With Health-Related Physical Fitness

BACKGROUND: To identify the clustering characteristics of individual-, family-, and school-level factors, and examine their associations with health-related physical fitness. METHODS: A total of 145,893 Chinese children and adolescents aged 9-18 years participated in this cross-sectional study. The 2-step cluster analysis was conducted to identify clusters among individual-, family-, and school-level factors. Physical fitness indicator was calculated through sex- and age-specific z scores of forced vital capacity, standing long jump, sit-and-reach flexibility, body muscle strength, endurance running, and body mass index. RESULTS: Three, 3, and 5 clusters were automatically identified at individual, family, and school levels, respectively. Students with low physical fitness indicator were more likely to be in the "longest sedentary time and skipping breakfast" cluster (odds ratio [OR] = 1.18; 95% confidence interval [CI], 1.12-1.24), and "physical inactivity and insufficient protein consumption" cluster (OR = 1.07; 95% CI, 1.02-1.12) at individual level, the "single children and high parental education level" cluster (OR = 1.15; 95% CI, 1.10-1.21), and "no physical activity support and preference" cluster (OR = 1.30; 95% CI, 1.25-1.36) at family level, and the "physical education occupied" cluster (OR = 1.06; 95% CI, 1.01-1.11), and "insufficient physical education frequency" cluster (OR = 1.16; 95% CI, 1.08-1.24) at school level. Girls were more vulnerable to individual- and school-level clusters, while boys were more susceptible to family clusters; the younger students were more sensitive to school clusters, and the older students were more susceptible to family clusters (P-interaction &lt; .05). CONCLUSIONS: This study confirmed different clusters at multilevel factors and proved their associations with health-related physical fitness, thus providing new perspective for developing targeted interventions.</p

Dramatic escalation in metabolic syndrome and cardiovascular risk in a Chinese population experiencing rapid economic development

Background Metabolic syndrome (MetSyn) increases the incidence of cardiovascular disease. Information on changes in prevalence of MetSyn in developing countries is limited. This study aims to compare MetSyn prevalence and its associated vascular risk over the period between 2002 and 2010 in a population which has had the world’s fastest economic development over the past three decades. Methods Two health surveys were conducted by using the multistage cluster random sampling method in a Chinese population of 85 million in southern China. The participants received a full medical check-up, including measurement of blood pressure (BP), obesity indices, fasting lipids and glucose levels. Data describing socio-economic status and lifestyle factors were also collected through interview. Metabolic syndrome was defined in accordance with the International Diabetes Federation criteria. Results A total of 3,561 participants from Survey 2010 were included in the data analysis. Women had a significantly higher prevalence of MetSyn than men. Comparison between the two surveys shows that age-standardized prevalence of MetSyn increased fourfold (from 5.4% in 2002 to 21.3% in 2010) in those ≧ 20 years. Among the MetSyn components, prevalence of hyperglycaemia has increased most (from 9.1% to 53.1%). The age-standardized prevalence of central obesity, hypertension, hypertriglyceridaemia and low HDL-cholesterol increased from 13.5% to 25.4%, from 23.6% to 40.8%, from 12.1% to 17.4% and from 32.1% to 71.1%, respectively. Differences between rural and urban residents in the prevalence in MetSyn and its components narrowed in 2010. Conclusions Cardiovascular risk escalated dramatically in this population between 2002 and 2010. The escalation may relate to the rapid economic development, which led to accelerating changes in nutrition, lifestyle, and socio-economic status. Our findings suggest that health transition in rapidly developing second- and third-world countries may be much faster than what has been observed in Western countries.published_or_final_versio

EZH2 protein: A promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies

Background and aims: A previous study of ours indicated that enhancer of zeste homologue 2 (EZH2) plays an important role in hepatocellular carcinoma (HCC) tumorigenesis. The aim of the present study was to investigate the potential diagnostic utility of EZH2 in HCC. Methods: Immunohistochemistry was performed to examine the expression dynamics of EZH2 in two independent surgical cohorts of HCC and non-malignant liver tissues to develop a diagnostic yield of EZH2, HSP70 and GPC3 for HCC detection. The diagnostic performances of EZH2 and a three-marker panel in HCC were re-evaluated by using an additional biopsy cohort. Results: Immunohistochemistry analysis demonstrated that the sensitivity and specificity of EZH2 for HCC detection was 95.8% and 97.8% in the testing cohort. Similar results were confirmed in the validation cohort. For diagnosis of well-differentiated HCCs, the sensitivity and specificity were 68.9% and 91.5% for EZH2, 62.5% and 98.5% for HSP70, 50.0% and 92.1% for GPC3, and 75.0% and 100% for a three-marker panel. In biopsies, positive cases for at least one marker increased from large regenerative nodule and hepatocellular adenoma (0/12) to focal nodular hyperplasia (2/20), dysplastic nodule (7/25), well-differentiated HCC (16/18) and moderately and poorly differentiated HCC (54/54). When at least two positive markers were considered, regardless of their identity, the positive cases were detected in 0/12 large regenerative nodules and hepatocellular adenomas, 0/20 focal nodular hyperplasias, 0/25 dysplastic nodules, 11/18 well-differentiated HCCs, 32/37 moderately differentiated HCCs and 15/17 poorly differentiated HCCs. Conclusion: Our findings suggest that EZH2 protein, as examined by immunohistochemistry, may serve as a promising diagnostic biomarker of HCCs, and the use of a three-marker panel (EZH2, HSP70 and GPC3) can improve the rate of detection of HCCs in liver biopsy tissues.published_or_final_versio

A foodborne outbreak of gastroenteritis caused by vibrio parahaemolyticus and norovirus through non-seafood vehicle

Foodborne outbreaks caused by a mixed infection of Vibrio parahaemolyticus and norovirus have rarely been described. We reported a mixed outbreak of Vibrio parahaemolyticus and norovirus causing acute gastroenteritis in 99 staff members of a company in Guangdong, China, in May 2013, following consumption of roasted duck, an uncommon non-seafood vehicle for such mixed infection, in one meal served in the company's catering service. Epidemiological and laboratory findings indicated that a single asymptomatic food handler was the source of both pathogens, and the high rate of infection of both pathogens was exacerbated by the setting's suboptimal food hygiene practice. © 2015 Liu et al.published_or_final_versio

Nonmonotone Barzilai-Borwein Gradient Algorithm for ℓ1\ell_1-Regularized Nonsmooth Minimization in Compressive Sensing

This paper is devoted to minimizing the sum of a smooth function and a nonsmooth $\ell_1$-regularized term. This problem as a special cases includes the $\ell_1$-regularized convex minimization problem in signal processing, compressive sensing, machine learning, data mining, etc. However, the non-differentiability of the $\ell_1$-norm causes more challenging especially in large problems encountered in many practical applications. This paper proposes, analyzes, and tests a Barzilai-Borwein gradient algorithm. At each iteration, the generated search direction enjoys descent property and can be easily derived by minimizing a local approximal quadratic model and simultaneously taking the favorable structure of the $\ell_1$-norm. Moreover, a nonmonotone line search technique is incorporated to find a suitable stepsize along this direction. The algorithm is easily performed, where the values of the objective function and the gradient of the smooth term are required at per-iteration. Under some conditions, the proposed algorithm is shown to be globally convergent. The limited experiments by using some nonconvex unconstrained problems from CUTEr library with additive $\ell_1$-regularization illustrate that the proposed algorithm performs quite well. Extensive experiments for $\ell_1$-regularized least squares problems in compressive sensing verify that our algorithm compares favorably with several state-of-the-art algorithms which are specifically designed in recent years.Comment: 20 page

STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al

Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

<p>Abstract</p> <p>Background</p> <p>Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As₂O₃) with cisplatin (DDP) on A549 and H460 non-small cell lung cancer (NSCLC) cells were explored.</p> <p>Methods</p> <p>A549 and H460 human lung cancer cells were treated with As₂O₃and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, clonogenic assay, and flow cytometry (FCM). Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot.</p> <p>Results</p> <p>MTT and clonogenic assay showed As₂O₃within 10^-2μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As₂O₃exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI) for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As₂O₃with DDP. FCM showed As₂O₃did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As₂O₃and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As₂O₃and/or DDP. FCM and TUNEL staining illustrated that the combination of As₂O₃and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As₂O₃and/or DDP treatments compared with controls. The expression of caspase-3 in cells treated with the combination of As₂O₃and DDP did not differ from that in cells treated with a single agent.</p> <p>Conclusion</p> <p>As₂O₃exerted synergistic effects with DDP on NSCLC cells, and the synergistic effects were partly due to the induction of caspase-independent apoptosis.</p