Pathological Differentiation Research Articles

The combination of a seven-autoantibody panel with computed tomography scanning can enhance the diagnostic efficiency of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is still of concern in differentiating it from benign disease. This study aims to validate the diagnostic efficacy of a novel seven-autoantibody (7-AAB) panel for the diagnosis of NSCLC. We retrospectively enrolled 2650 patients who underwent both the 7-AAB panel test and CT scanning. We compared the sensitivity, specificity, and PPV of 7-AAB, CT, and PET-CT in the diagnosis of NSCLC in different subgroups. Then, we established a nomogram based on CT image features and the 7-AAB panel to further improve diagnostic efficiency. Moreover, we compared the pathological and molecular results of NSCLC patients in the 7-AABs positive group and the negative group to verify the prognostic value of the 7-AAB panel. The strategy of a "both-positive rule" combination of 7-AABs and CT had a specificity of 95.4% and a positive predictive value (PPV) of 95.8%, significantly higher than those of CT or PET-CT used alone (P<0.05). The nomogram we established has passed the calibration test (P=0.987>0.05) with an AUC of 0.791. Interestingly, it was found that the 7-AABs positive group was associated with higher proportion of EGFR mutations (P<0.001), lower pathological differentiation degrees (P=0.018), more advanced pathological stages (P=0.040) and higher Ki-67 indexes (P=0.011) in patients with adenocarcinoma. This study shows that combination of a 7-AAB panel with CT has can significantly enhance the diagnostic efficiency of lung cancer. Moreover, the 7-AAB panel also has potential prognostic value and has reference significance for the formulation of the treatment plan.

KTN1-AS1, a SOX2-mediated lncRNA, activates epithelial–mesenchymal transition process in esophageal squamous cell carcinoma

Kinectin 1 antisense RNA 1 (KTN1-AS1), a long non-coding RNA (lncRNA), has been proved to have tumor-promoting properties and its expression is enhanced in several human tumors. However, the role of KTN1-AS1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC) remains unknown. This study aimed to investigate the expression status, functional roles, and molecular mechanisms of KTN1-AS1 in the development of ESCC. Considerable upregulation of KTN1-AS1 was confirmed in esophageal cancer cells and ESCC tissues and its expression was associated with TNM stage, pathological differentiation, and lymph node metastasis. SOX2 directly activated transcription of KTN1-AS1, and overexpression of KTN1-AS1 facilitated ESCC cells proliferation and invasion in vitro and in vivo. Furthermore, KTN1-AS1 could bind to retinoblastoma binding protein 4 (RBBP4) in the nucleus and enhanced its binding with histone deacetylase 1 (HDAC1), thereby activating the epithelial–mesenchymal transition (EMT) process through downregulating E-cadherin expression at the epigenetic level. In conclusion, KTN1-AS1, induced by SOX2, acts as a tumor-promoting gene and may serve as a potential therapeutic and prognostic biomarker for ESCC.

Idiopathic Multicentric Castleman Disease Interactive Disease Awareness and Educational Tool for Pathologists

Background: Idiopathic multicentric Castleman disease (iMCD) is a rare systemic lymphoproliferative disease that is challenging to diagnose. Diagnostic criteria require the identification of characteristic histopathology in the context of supportive clinical, radiologic, and serologic findings. However, the histologic features of iMCD can be subtle and nonspecific, which delays an accurate diagnosis. Timely diagnosis and early intervention are essential to reduce patient mortality. Developing a disease awareness and educational tool for pathologists may support the identification of future iMCD cases. Methods: International pathologists were identified to support the development of an interactive pathology tool for iMCD. To validate the tool, a selection of pathologists attended a virtual workshop to provide insight and help shape the content and format of the tool. Prior to workshop, attendees were asked to complete a 14-question survey on the diagnosis of iMCD, including exclusion of other diseases, conditions with similar histopathological features, and features specific to iMCD. Results: The educational tool is currently in development and takes into consideration the varied diagnostic journeys in different centers/countries. Histopathologic criteria for iMCD require evaluation of the degree of plasmacytosis, regressed germinal centers, follicular dendritic cell proliferation, vascular proliferation, and hyperplastic germinal centers. While the differences between high grade (grade 3) and normal (grade 0) findings are straightforward, differentiating grade 1 from grade 2 (the diagnostic cut-off) is challenging and subjective. The tool will focus on these diagnostic grey-zones to include points of differentiation between Grades 1 and 2 iMCD, disease exclusion criteria, and the use of diagnostic images that can be explored. Thus far, development of the tool has shown there is a need for standardized disease terminology between pathologists, that the use of template reports and language guidance may support the diagnostic process, and that patient case studies and the use of real-world examples support disease recognition. The educational tool is anticipated to be ready for release in September 2022. Conclusions: Diagnosis of iMCD is complex, and, despite the existence of well-established diagnostic criteria, pathological differentiation remains a challenge. Increasing awareness of iMCD-specifically the key diagnostic criteria-will assist with both timely diagnoses and the treatment of this disease.

Diagnosis and differentiation diagnosis of primary temporomandibular joint cartilage and giant cell related tumor lesions

Cartilage and giant cell-related neoplastic lesions originating in the temporomandibular joint region have similar clinical, imaging and pathological manifestations, making the diagnosis of these disorders challenging to varying degrees. Diagnostic findings can influence treatment procedures and a definitive pathological diagnosis is important for the prognosis of these conditions. In this article, we discuss the pathological diagnosis and differentiation of four benign cartilage and giant cell related tumors and tumor-like lesions that occur in the temporomandibular joint, namely synovial chondromatosis, tumoral calcium pyrophosphate deposition disease, pigmented villonodular synovitis and chondroblastoma, taking into account their clinical features and histological manifestations, with a view to providing a basis for clinical management.

The Occurrence of Activated Leukocyte Cell Adhesion Molecule (ALCAM) and Its Predictive Factors in Patients with Oral Squamous Cell Carcinoma.

To determine the occurrence of Activated Leukocyte Cell Adhesion Molecule (ALCAM) and its predictive factors in patients with oral squamous cell carcinoma (OSCC). This cross sectional study was concocted on 102 patients with OSCC referred to Imam Khomeini Hospital of Tehran during 1997-2015. The data collection tool a checklist consisted of demographic and pathologic (lymph node involvement, differentiation, tumor size and tumor location) characteristics which extracted from patients' medical records. To evaluate ALCAM, a new sample of tumor tissue was prepared from archive. Finally, the multivariable logistic regression model was used to determine the predictive factors of ALCAM by STATA14. the number (%) of men and women were 70 (68.6) and 32 (31.4%), respectively. The mean age (S.D) of participants was 61.7 (15.6) years. Of the total samples, 32 (38.2), 19 (18.6), 36 (35.3) and 8 (7.8%) samples were related to the tongue, oral mucosa, skin and lips, respectively. More than half of the tumors had good differentiation and lymph node involvement and 74.5% were ≥20 mm. Also, 79.41% of the samples were positive for the overall incidence of ALCAM. The most important predictors of the overall incidence of ALCAM were tumor size (OR: 3.46, 95% CI: 1.71 - 7.01) and tumor location (OR: 3, 95% CI: 1.03 - 8.72). Similarly, for incidence of cytoplasmic ALCAM were age (OR: 2.56, 95% CI: 1.38 - 4.76) and location of the tumor (OR: 3.23, 95% CI: 1.08 - 9.64). However, the only predictor of membranous ALCAM incidence was lymph node involvement (OR: 0.36, 95% CI: 0.19 - 0.66). The results of our study suggest preliminary evidence for the potential clinical application of ALCAM as a prognostic biomarker for OSCC which may be the basis for future clinical application, however further studies are recommended.

Pool of bile acids, its predictor functions and influence on the pathology of the hepatobiliary system (review)

The creation of a highly effective model for diagnosing liver diseases of various genesis (including subclinical forms) in animals is one of the most urgent problems of veterinary science. Currently, there is a need to create more specific than "classical" tests for a clear differentiation of various pathologies of the hepatobiliary system, including diseases characterized by the absence of pathognomonic clinical or laboratory signs. One of the extremely promising predictors of such pathologies is bile acids (BA) and their pool. The main goal of the study is to search and analyze information from scientific publications dedicated to the study of the BA’s pool in various animal species, its changes in various pathologies of the hepatobiliary system and its diagnostic value. In English and Russian, in accordance with the recommendations of H. Snyder, various bibliographic databases (Elibrary, Pubmed, Scopus (Elsevier), Web of Science (Clarivat)) were searched for thematic publications by keywords with further highlighting the most cited ones. Articles published before 2015 were used only if they contained information critical to the better understanding of the topic, or it was not found in later publications. Based on the literature analysis, it can be concluded that liver diseases affect the synthesis and metabolism of bile acids. Therefore, BAs separately and their pool are studied and utilized as diagnostic and prognostic markers. However, it is not yet clear how the etiology of liver diseases affects the composition of bile acids. It should also be noted that in different animals there are differences in the BA pool, as well as in the details of their metabolism. This indicates differences in the specificity, affinity, and activity of enzymes involved in BA synthesis. Thus, BAs also affect the etiopathogenesis of diseases of the hepatobiliary system differently for each animal species, and, conversely, etiopathogenetic factors change the pool of BAs depending on the individual characteristics of the species.

A Radiomics-Based Nomogram for the Prediction of Occult Lymph Node Metastasis in cN0 Supraglottic Carcinoma

<h3>Purpose/Objective(s)</h3> To develop a radiomics-based nomogram for predicting pathologically occult lymph node metastasis in patients with cN0 supraglottic carcinoma (SGC) to inform the optimal neck treatment. <h3>Materials/Methods</h3> The training set included 131 patients with SGC from 1/2010 to 12/2019 in our hospital, and the validation set included 108 patients from the same time in other hospital. All patents with cN0, defined by computed tomography (CT) and ultrasound or magnetic resonance imaging of the neck, had positive pathologically lymph node. The primary tumors of ROI regions were outlined in each patient's CT image by two radiotherapists. Using the least absolute shrinkage and selection operator (LASSO) method to select radiomics features. The multivariable logistic regression analysis was adopted to develop a radiomics nomogram combining radiomics score and clinical variables. The predictive performance of the model was evaluated by the calibration and decision curve analysis. <h3>Results</h3> Four radiomics features were selected to constitute radiomics signature, which was associated with LNM. Clinical T stage and pathology differentiation were also significant associated with occult metastasis, founded by multivariable logistic analysis. The multiparametric radiomics nomogram incorporate these factors and radiomics signature, which showing better prediction efficacy (C-index 0.805, 95%CI: 0.720-0.890) than radiomics score alone (C-index 0.776, 95%CI: 0.686-0.866) in training set. The area under curve yielded was 0.767 (95%CI: 0.666-0.869) in the validation set. Decision curve analysis showed our model achieved favorable discrimination and calibration. <h3>Conclusion</h3> The radiomics-based nomogram including radiomics signature, clinical T stage, and pathology differentiation has favorable individualized prediction of occult LNM in cN0 SGC patients. This nomogram could offer optimal neck dissection and prophylactic neck irradiation for cN0 SGC patients.

Objective Quantitative Analysis of Laryngeal Glottal Gaps using High-Speed Video in Glottal Analysis Tools, a Case-Control Study

Quantitative voice analysis for clinical use has been focused upon for many years. The aim was to test if Glottal Analysis Tools (GAT) could be used, based on High-Speed Video (HSV) to quantify distances between the vocal folds at any place on the vocal folds. The software includes a reproduced computed film of the vocal fold movements online. 20 normal HSV and 30 with insufficient closure in the rear part of the vocal folds (rear glottal gap) were compared in a case-control study. The distance of trajectories was chosen at 50% and 10% from the rear part of the glottis and maximum and minimum distances between the vocal folds were defined during phonation in the 2 groups. It was possible to calculate the absolute data of insufficiency of closure of the vocal folds compared to normal HSV with a statistical difference of p&lt;0,0001. An interesting result was in this material also that functional closure was found in all images in the middle of the vocal folds. In the future quantification of voice disorders should include specific parts of the Glottal Area Waveform (GAW) analyses based on HSV for better differentiation of function and pathology of the vocal folds.

Clinicopathological and prognostic value of lncRNAs expression in gastric cancer: A field synopsis of observational studies and databases validation.

Background:The purpose of this study was to evaluate existing evidence in the field of long non-coding RNAs (lncRNAs) and prognosis of gastric cancer.Methods:A comprehensive literature search was performed through the electronic database. The combined hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of overall survival (OS), disease-free survival (DFS), or progression free survival (PFS) were calculated to assess the strength of the association. Kaplan–Meier (KM) plotter was used to verify lncRNA HOX transcript antisense RNA (HOTAIR) expression and OS.Results:Overall, a significant correlation between high lncRNAs expression and poor OS was explored in patients with gastric cancer (HR = 1.78, P < .001). Subgroup analysis based on statistical methods indicated the high expression of lncRNAs in log-rank (HR = 1.87, P < .001) and multivariate analysis (HR = 1.71, P < .001) were all significantly correlated with the poor OS. Clinicopathological parameters analysis showed the lncRNA expression were significantly associated prognosis, including TNM stage, tumor size, pathological differentiation, lymph nodes metastasis, distance metastasis, invasion depth and Lauren’s classification. It was consistent with the verification results of bioinformatics database for lncRNA HOTAIR (P < .001).Conclusion:Our study confirmed the expression of lncRNAs and clinicopathological features may serve as effective indicators of prognosis in patients with gastric cancer.

Correlation Study on the Expression of INSR, IRS-1, and PD-L1 in Nonsmall Cell Lung Cancer.

Objective To study the expression and correlation of insulin receptor (INSR), insulin receptor substrate-1 (IRS-1), and programmed cell death ligand-1 (PD-L1) in nonsmall cell lung cancer (NSCLC). Methods 45 lung cancer tissues and 30 adjacent normal tissues of NSCLC patients diagnosed in the Second Affiliated Hospital of Shandong First Medical University from June 2019 to August 2020 were selected. The expressions of INSR, IRS-1, and PD-L1 proteins in tumor tissues and adjacent tissues of NSCLC were detected by immunohistochemical staining. Results The expression of INSR and IRS-1 in NSCLC was significantly higher than that in adjacent normal lung tissue (P < 0.05). INSR expression had statistical significance with the degree of pathological differentiation of nonsmall cell carcinoma (P = 0.031), but had no significant association with age, gender, pathological type, TNM stage, and lymph node metastasis status (P > 0.05). There was no significant correlation between IRS-1 positive expression and NSCLC patients' age, gender, pathological typing, degree of differentiation, TNM stage, and lymph node metastasis (P > 0.05). PD-L1 positive expression was correlated with lymph node metastasis of NSCLC (P = 0.028), while there was no significant correlation with gender, age, pathological type, TNM stage, and pathological differentiation degree of NSCLC patients (P > 0.05). Spearman correlation analysis showed that PD-L1 protein expression had a significant positive correlation with IRS-1 protein expression (r = 0.373), but was not correlated with the expression of INSR protein. Conclusion IRS-1 may be involved in the regulation of PD-L1 expression and mediate the occurrence of tumor immune escape, which is expected to become a new target for NSCLC immunotherapy and provide new clinical evidence for immunosuppressive therapy.

Metastatic undifferentiated pleomorphic sarcoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

Pathological differentiation is important for suspected lesions of metastatic undifferentiated pleomorphic sarcoma (UPS) because no reliable imaging criteria exist for this entity yet. In the present case, transgastric endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for the pancreatic tumor and transcolonic EUS-FNA for the intraabdominal tumor contributed to the definitive diagnosis of metastatic UPS, leading to appropriate treatment selection.

Investigation of clinical application of claudin 18 isoform 2 in pancreatic ductal adenocarcinoma: A retrospective analysis of 302 chinese patients.

The malignancy of pancreatic ductal adenocarcinoma (PDAC) results from high frequency of recurrence and limited effective therapies. Targeted therapy is a promising treatment in multiple solid tumours. A new target, claudin 18 isoform 2 (CLDN18.2) was discovered in gastric and pancreatic adenocarcinoma, but more clinical evaluations of CLDN18.2 are still needed. Several CLDN18.2-targeted drugs have already been in procedure of clinical trials. Therefore, the present study aimed to explore the expression and clinical value of CLDN18.2 in PDAC by immunohistochemistry. A microarray cohort of 302 PDAC specimens and a whole-slide cohort of randomized 84 PDAC specimens were constructed. In total, 56.52% (171/302) of PDAC patients showed diverse positivity for CLDN18.2, especially in highly differentiated PDAC. About eighty-two percent (62/75) highly- and 62.61% (72/115) intermediate-differentiated PDAC showed positive for CLDN18.2, while only 10.16% (6/59) low differentiated PDAC was positive for CLDN18.2. Besides, CLDN18.2 positivity was associated with several clinicopathological characteristics, including sex (P=0.001), smoking (P=0.006), abdominal pain (P=0.021), jaundice (P=0.010), pathological differentiation (P=0.001), common bile duct invasion (P=0.010), and M stage (P=0.003). CLDN18.2-positive expression also predicts an improved survival (P=0.032) but not progression free survival (P=0.460). However, CLDN18.2 is not an independent prognostic predictor. In conclusion, CLDN18.2 may be a potential therapeutic target for PDAC and the study supplies persuasive pathological evidence for CLDN18.2-targeted therapy on PDAC patients.

CIMP-positive glioma is associated with better prognosis: A systematic analysis.

Background:CpG island methylator phenotype (CIMP) was closely related to the degree of pathological differentiation of tumors, and it’s an important determinant of glioma pathogenicity. However, the molecular and pathological features of CIMP-positive glioma have not been fully elucidated. In addition, CIMP have been reported to be a useful prognostic marker in several human cancers, yet its prognostic value in gliomas is still controversial. Therefore, we aimed to evaluate gene mutations and pathological features of CIMP-positive glioma and explore the prognostic value of CIMP in gliomas.Methods:We comprehensively searched PubMed, Embase, and MEDLINE for studies describing gene mutations, pathological features and overall survival of gliomas stratified by CIMP status. Odds ratios (OR), hazard ratios (HR), and their 95% confidence intervals (CI) were used to estimate the correlation between CIMP and the outcome parameters.Results:Twelve studies with 2386 gliomas (1051 CIMP-positive and 1335 CIMP-negative) were included. Our results showed that CIMP was more frequent in isocitrate dehydrogenase 1 (IDH1)-mutated gliomas (OR 229.07; 95% CI 138.72–378.26) and 1p19q loss of heterozygosis (LOH) gliomas (OR 5.65; 95% CI 2.66–12.01). Pathological analysis showed that CIMP was common in low-malignant oligodendroglioma (OR 5.51; 95% CI 3.95–7.70) with molecular features including IDH1 mutations and 1p19q LOH, but rare in glioblastoma (OR 0.14; 95% CI 0.10–0.19). However, CIMP showed no obvious correlation with anaplastic oligoastrocytomas (OR 1.57; 95% CI 1.24–2.00) or oligoastrocytomas (OR 0.79; 95% CI 0.35–1.76). Concerning the prognosis, we found that CIMP-positive gliomas had longer overall survival (HR 0.57; 95% CI 0.97–0.16) than CIMP-negative gliomas.Conclusions:CIMP could be used as a potential independent prognostic indicator for glioma.

Prognostic and clinicopathological significance of transcription factor c-Jun in hypopharyngeal squamous cell carcinoma: a 3-year follow-up retrospective study.

PurposeTo investigate the expression and prognostic value of c-Jun in hypopharyngeal squamous cell carcinoma (HPSCC).MethodsA retrospective study was performed on a cohort of 99 HPSCC patients. The expression of c-Jun and phosphorylated-c-Jun (p-c-Jun) was evaluated via immunohistochemistry (IHC) staining. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier method and multivariate Cox regression analysis.ResultsThe high expression of c-Jun and p-c-Jun in HPSCC accounted for 60.61% and 16.16%, respectively. High expression of c-Jun was closely associated with cT stage (p = 0.0401), tumor size (p = 0.0276), number of lymph node metastases (p = 0.0205) and pathological differentiation (p = 0.0108). The expression of c-Junhigh (p = 0.0043), p-c-Junhigh (p = 0.0376) and c-Junhigh/p-c-Junhigh were closely associated with poor OS. The Cox proportional multivariate hazard model revealed that lymphovascular invasion and c-Jun expression were independent influencing factors of OS in HPSCC patients.ConclusionOur findings suggest that c-Jun is a reliable prognostic factors in HPSCC patients.

Caffeic Acid Inhibits Swelling, Bone Loss, and Osteoclastogenesis in Adjuvant-induced Arthritis Rats

BACKGROUND: Increase in inflammatory cytokine levels promotes pathological osteoclast differentiation. Caffeic acid has anti-inflammatory properties and can inhibit osteoclast bone resorption. In vitro studies have reported the ability of caffeic acid in inhibiting osteoclastogenesis pathways, however the in vivo study is rarely conducted. The aim of this study is to examine the role of caffeic acid in reducing inflammation and inhibiting osteoclastogenesis in Adjuvant-Induced Arthritis (AIA) rats.METHODS: Rats were injected with Freund’s Complete Adjuvant (CFA) and mineral oil. One day after injection, various concentration (0, 5, 25, 125 mg) of caffeic acid were given gastro-intestinally. Swelling degree in rats’ ankle joints was determined by measuring height and width of each ankle joint. Bone loss level was examined with soft X-ray, and then bone density was calculated. To examine osteoclastogenesis, ankle joints were stained with Tartrate-Resistant Acid Phosphatase (TRAP) and evaluated microscopically. RESULTS: Ankle joints of AIA rats had severe swelling before treated, yet the swelling was reduced based on concentration-dependent after receiving caffeic acid. Severe bone loss in AIA rats’ ankle joints were also observed, however the treatment of 125 mg caffeic acid showed remarkable inhibition effect toward rats’ bone loss. Osteoclastogenesis in AIA rats’ ankle joints were higher than the normal ones, as indicated with high TRAP-positive Multinucleated Cells (MNCs). But low number of TRAP-positive MNCs was observed in ankle joint of AIA rats that received 125 mg caffeic acid.CONCLUSION: Administration of caffeic acid can reduce the degree of swallowing, inhibit bone loss, and inhibit osteoclastogenesis in ankle joint of arthritis-induced rats.KEYWORDS: caffeic acid, osteoclastogenesis, bone loss, swelling, inflammation, RANKL, TNF-α

Impact of D-dimer for pathologic differentiation on transesophageal echocardiography in embolic stroke of undetermined source: a single-center experience

BackgroundEmbolic stroke of undetermined source (ESUS) encompasses diverse embologenic mechanisms, which transesophageal echocardiography (TEE) is critical to detect. Specific markers related to each embolic source in ESUS is not fully studied. We focused on D-dimer levels, and explored the association of D-dimer with potential embolic sources (PES) identified on TEE in ESUS.MethodsConsecutive patients with ESUS were included in this study. Clinical characteristics including D-dimer levels were compared between ESUS patients with and without TEE, and among none of, one, and at least two PES in ESUS patients undergoing TEE. Factors related to elevation of D-dimer were analyzed.ResultsA total of 211 patients (age, 69.3 ± 13.2 years; 149 males) with ESUS were enrolled. Of these, 115 received TEE, displaying significantly younger age and lower D-dimer levels than patients without TEE (P < 0.05), and 20 (17%), 61 (53%), and 34 (30%) patients were classified into none of, one, and ≥ two PES, respectively. On multiple logistic regression analysis, D-dimer levels were related to one PES (odds ratio [OR]: 9.01; 95% confidence interval [CI]: 1.00–81.51; P = 0.050) and PES ≥ two (OR: 9.76; 95% CI: 1.07–88.97; P = 0.043). Right-to-left shunt (RLS) with deep venous thrombosis (DVT)(OR: 13.94; 95% CI: 1.77–109.99; P = 0.012) and without DVT (OR: 3.90; 95% CI: 1.20–12.70; P = 0.024) were associated with elevation of D-dimer.ConclusionsD-dimer levels were higher in patients with PES. Among PES, RLS, with and without DVT, were associated with increase of D-dimer in ESUS.

Is Strain Elastography Useful in Diagnosing Chronic Autoimmune Thyroiditis in Children?

Strain elastography (SE) determines the level of tissue stiffness and thus helps in the diagnosis and differentiation of various pathologies. This paper aims to study the elastographic differences between healthy thyroid parenchyma and ones affected by chronic autoimmune thyroiditis (CAT) in children. We included in our study 52 children diagnosed with CAT and 22 children with no thyroid pathology. After clinic examination and biological tests, an ultrasound was performed followed by SE using a Hitachi Preirus machine with a 5–15 multi-frequency linear probe. The mean strain ratio (SR) values were significantly lower in the control group compared with the CAT group (0.68 ± 0.2 vs. 1.19 ± 0.25; p &lt; 0.0001). A mean value above 0.9 was found predictive for CAT with 84.62% Sensitivity(Se), 95.45% Specificity (Sp), 97.8% Positive Predictive Value (PPV), 72.4% Negative Predictive Value (NPV), and area under receiver operating characteristic (AUROC), 0.9. No differences were found between the two thyroid lobes. Also, we found no differences between girls and boys. Out of the 52 children with CAT, 39 were on therapy with levothyroxine. No differences were found between SR values in preexisting hypothyroid cases compared to euthyroid cases (1.24 ± 0.26 vs. 1.18 ± 0.25; p = 0.4615). Our results show that SE is a useful examination technique of children diagnosed with CAT, in accordance with other studies conducted on adults. This study lays the foundation for elastographic examination among children.

Family history of malignant tumor is a predictor of gastric cancer prognosis: Incorporation into a nomogram.

The purpose of this study was to investigate the impact of a family history of malignant tumor on the prognosis of patients with gastric cancer and develop a nomogram that incorporates a family history of malignant tumor to predict overall survival (OS) in patients with gastric cancer to aid clinicians and patients in decision making. Four hundred eighty-eight patients with gastric cancer undergoing radical gastrectomy in our center were included and randomly split into a training set (n = 350) and a validation set (n = 138) at a ratio of 7:3. Cox univariate regression analysis was used to evaluate the influence of clinicopathological characteristics and family history of malignant tumors on their prognosis, and variables were screened by multivariate Cox regression analysis and consensus on clinical evidence. A nomogram was constructed for OS based on the filtered variables, and the C-index, receiver operating characteristic curve (ROC curve), and calibration curve were used to validate the nomogram and decision curve analysis curve (DCA curve) was used for clinical practicality assessment. Six variables related to OS, including the pathological differentiation degree, Lauren type, infiltration depth, lymph node metastasis, tumor deposit, and family history of malignant tumor, were screened to construct a nomogram. The nomogram developed in this study performed well in the training set and the validation set, with C-index of 0.776 and 0.757, and the area under the ROC curve(AUC) for predicting 1-, 3-, and 5-year survival rates are 0.838, 0.850, 0.820 and 0.754, 0.789, 0.808, respectively. The calibration curve shows that the estimated death risk of the nomogram in the 2 data sets is very close to the actual death risk. The net benefits of nomogram-guided prediction of patient survival at 1-, 3-, and 5 years were demonstrated by the DCA curves, which showed high clinical practicability. Family history of malignant tumors is an independent risk factor affecting the prognosis of patients with gastric cancer. The nomogram developed in this research can be used as an important tool to predict the prognosis of gastric cancer patients with family history data.

Emerging roles of long non-coding RNAs in keloids.

Keloids are pathologic wound healing conditions caused by fibroblast hyperproliferation and excess collagen deposition following skin injury or irritation, which significantly impact patients by causing psychosocial and functional distress. Extracellular matrix (ECM) deposition and human fibroblast proliferation represents the main pathophysiology of keloid. Long non-coding RNAs (LncRNAs) play important roles in many biological and pathological processes, including development, differentiation and carcinogenesis. Recently, accumulating evidences have demonstrated that deregulated lncRNAs contribute to keloids formation. The present review summarizes the researches of deregulated lncRNAs in keloid. Exploring lncRNA-based methods hold promise as new effective therapies against keloid.

Design, synthesis and biological evaluation of acyl hydrazones-based derivatives as RXRα-targeted anti-mitotic agents

RXRα, a unique and important nuclear receptor, plays a vital role in various biological and pathological pathways, including growth, differentiation, and apoptosis. We recently reported a transcription-independent function of RXRα in cancer cells in which RXRα is phosphorylated by Cdk1 at the onset of mitosis, resulting in its translocation to the centrosome, where the phosphorylated RXRα (p-RXRα) interacts with polo-like kinase 1 (PLK1) to promote centrosome maturation and mitotic progression. Significantly, we also identified that a small molecule XS-060 binds to RXRα and selectively inhibits the p-RXRα/PLK1 interaction to induce mitotic arrest and catastrophe in cancer cells. Here, we report our design, synthesis, and biological evaluation of a series of XS-060 analogs as RXRα-targeted anti-mitotic agents. Our results identified B10 as an improved anti-mitotic agent. B10 bound to RXRα (Kd = 3.04 ± 0.58 μM) and inhibited the growth of cervical cancer cells (HeLa, IC50 = 1.46 ± 0.10 μM) and hepatoma cells (HepG2, IC50 = 3.89 ± 0.45 μM and SK-hep-1, IC50 = 5.74 ± 0.50 μM) with low cytotoxicity to nonmalignant cells(LO2, IC50 > 50 μM). Furthermore, our mechanistic studies confirmed that B10 acted as an anticancer agent by inhibiting the p-RXRα/PLK1 pathway. These results provide a basis for further investigation and optimization of RXRα-targeted anti-mitotic molecules for cancer therapy.