Alleles ; Amelogenin/genetics* ; Chromosomes, Human, Y ; Humans ; Male ; Sex Determination Analysis

OBJECTIVETo investigate the expression of vascular endothelial growth factor D (VEGF-D) in human esophageal squamous cell carcinoma (ESCC) and its significance.

METHODSThe expression of VEGF-C mRNA in tumor tissues and non-cancer tissues from 39 ESCC patients in our hospital from March 2009 to February 2010 was detected by in situ hybridization (ISH) method. The expression of D2-40 was detected by immunohistochemistry,and microlymphatic vessel density (MLVD) was determined by lymphatic endothelial specific marker D2-40. The associations of VEGF-C mRNA expression with clinical data and MLVD were analyzed.

RESULTSPositive ISH VEGF-D mRNA was observed in tumor tissue samples of 22 cases (56.4%, 22/39) and non-cancer tissue sample of 1 case (2.6%, 1/39), whose difference was statistically significant (P<0.05). The expression of VEGF-D mRNA in ESCC was significantly associated with lymph node metastasis [92.9% (13/14) vs. 36.0% (9/25), P<0.05] and MLVD [(8.20±1.22) vs. (5.31±0.97), P<0.01], but not significantly associated with age, sex, pathological grade and depth of infiltration.

CONCLUSIONVEGF-D can promote lymphatic metastasis of ESSC by induction of lymphangiogenesis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; Esophageal Neoplasms ; metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Vascular Endothelial Growth Factor D ; metabolism

Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to infection. The development of sepsis is closely linked to immune dysfunction. As a result, immunotherapy has gained traction as a promising approach to sepsis treatment, as it holds the potential to reverse immunosuppression and restore immune balance, thereby improving the prognosis of septic patients. However, due to the highly heterogeneous nature of sepsis, it is crucial to carefully select the appropriate patient population for immunotherapy. This review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians' understanding and practical application of immunotherapy in the management of sepsis.

BACKGROUNDCathepsin B plays an important role in cell cycle, extracellular matrix changes and cutaneous tumorigenesis: whether it plays a role in photoaged skin remains unknown. This study aimed to investigate the role of cathepsin B in skin photoaging in vivo and in vitro.

METHODSThe expressions of cathepsin B were compared with immunohistochemical methods in solar exposed skin and solar protected skin of six healthy Chinese volunteers. The mRNA and protein expression of cathepsin B in ultraviolet light A (UVA) induced premature senescence fibroblasts in vitro were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting technique.

RESULTSDecreased expression of cathepsin B was observed in photoaged skin compared with that of the solar protected skin. In the UVA induced, premature senescence fibroblasts, a lower expression of cathepsin B was detected by Western blotting and a decreased synthesis of cathepsin B mRNA in the same cells was revealed by real-time RT-PCR.

CONCLUSIONSThe results demonstrated a significant negative correlation between skin photoaging and cathepsin B in vitro and in vivo. We propose that cathepsin B, besides matrix metalloproteinases and antioxidant enzymes, is involved in the process of skin photoaging in that it contributes to extracellular matrix remodelling and is a dominant protease in cellular apoptosis and senescence.

Blotting, Western ; Cathepsin B ; analysis ; genetics ; physiology ; Female ; Fibroblasts ; radiation effects ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Skin ; radiation effects ; Skin Aging ; Ultraviolet Rays ; beta-Galactosidase ; analysis

OBJECTIVETo investigate the effects of Trichophyton rubrum exposure on the expressions of toll-like receptor-2 (TLR-2), TLR-4 and dendritic cell associated C-type lectin-1 (Dectin-1) and cytokine secretions in human keratinocytes cell line HaCaT.

METHODSThe mRNA of TLR-2,4, and dectin-1 in the HaCaT co-cultured with the conidia of Trichophyton rubrum conidia for 24 h was measured with real-time PCR. The mean fluorescence intensity and the percentage of cells positive for TLR-2, 4, and dectin-1 was detected during the co-culture using flow cytometry. The cytokine secretion profiles in the cell culture supernatant was analyzed using a cytokine antibody array.

RESULTSThe TLR-2,4, and dectin-1 mRNA expressions, mean fluorescence intensity and percentage of positive cells for TLR-2,4, and dectin-1 all increased in HaCaT cells in response to Trichophyton rubrum conidia exposure. The results of cytokine antibody array demonstrated obviously increased secretions of IL-8, I-309, IFN-γ, IL-6, and IL-13 in the culture supernatant of HaCaT cells in response to Trichophyton rubrum exposure.

CONCLUSIONThe immune responses and immunological recognition of human keratinocytes to Trichophyton rubrum conidia are partially mediated by up-regulating the expressions of TLR-2, TLR-4 and dectin-1 and secretions of multiple cytokines.

Cell Line ; Chemokine CCL1 ; secretion ; Coculture Techniques ; Humans ; Interferon-gamma ; secretion ; Interleukin-13 ; secretion ; Interleukin-6 ; secretion ; Interleukin-8 ; secretion ; Keratinocytes ; metabolism ; Lectins, C-Type ; metabolism ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 4 ; metabolism ; Trichophyton ; Tumor Necrosis Factor-alpha ; secretion

Systems biology has become an effective approach for understanding the molecular mechanisms underlying the development of lung cancer. In this study, sequences of 100 non-small cell lung cancer (NSCLC)-related proteins were downloaded from the National Center for Biotechnology Information (NCBI) databases. The Theory of Coevolution was then used to build a protein-protein interaction (PPI) network of NSCLC. Adopting the reverse thinking approach, we analyzed the NSCLC proteins one at a time. Fifteen key proteins were identified and categorized into a special protein family F(K), which included Cyclin D1 (CCND1), E-cadherin (CDH1), Cyclin-dependent kinase inhibitor 2A (CDKN2A), chemokine (C-X-C motif) ligand 12 (CXCL12), epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), TNF receptor superfamily, member 6(FAS), FK506 binding protein 12-rapamycin associated protein 1 (FRAP1), O-6-methylguanine-DNA methyltransferase (MGMT), parkinson protein 2, E3 ubiquitin protein ligase (PARK2), phosphatase and tensin homolog (PTEN), calcium channel voltage-dependent alpha 2/delta subunit 2 (CACNA2D2), tubulin beta class I (TUBB), SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 2 (SMARCA2), and wingless-type MMTV integration site family, member 7A (WNT7A). Seven key nodes of the sub-network were identified, which included PARK2, WNT7A, SMARCA2, FRAP1, CDKN2A, CCND1, and EGFR. The PPI predictions of EGFR-EGF, PARK2-FAS, PTEN-FAS, and CACNA2D2-CDH1 were confirmed experimentally by retrieving the Biological General Repository for Interaction Datasets (BioGRID) and PubMed databases. We proposed that the 7 proteins could serve as potential diagnostic molecular markers for NSCLC. In accordance with the developmental mode of lung cancer established by Sekine et al., we assumed that the occurrence and development of lung cancer were linked not only to gene loss in the 3p region (WNT7A, 3p25) and genetic mutations in the 9p region but also to similar events in the regions of 1p36.2 (FRAP1), 6q25.2-q27 (PARK2), and 11q13 (CCND1). Lastly, the invasion or metastasis of lung cancer happened.
Biomarkers, Tumor ; metabolism ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; Databases, Factual ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Protein Interaction Maps

Purpose: This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE). Materials and Methods: From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA). Results: Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness. Conclusion Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

Adult ; Aged ; Aqueous Humor ; virology ; Female ; Humans ; Immunocompetence ; immunology ; Inflammation ; virology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the imaging features, clinical manifestations and pathological characteristics of solitary fibrous tumors (SFT).

METHODSThe clinicopathological manifestations and medical imaging findings were analyzed retrospectively in 27 patients with surgically confirmed SFT.

RESULTSThe SFTs originated from different parts of the body, including 18 in the chest, 4 in the abdomen, 1 in the lumboscral area, 3 in the pelvis, and 1 in the left shoulder. Twenty-three cases were found by CT scan, among which there were 16 benign diseases, presented with well-defined round or elliptic margins, with homogeneous attenuation and clearly surrounding; 6 malignant cases with unclear demarcations, invasive surrounding, heterogeneous attenuation due to calcification and/or irregular necrosis, and 1 junctional case with well-defined margins, which was enlarged during follow-up. There were 4 SFTs scanned by MRI with clear margin and homogeneous or heterogeneous signal intensity. All of the 4 cases were isointense or hyperintense to muscle on T1-weighted images, and were hyperintense on the T2-weighted images. All tumors showed heterogeneously intense enhancement with geographic pattern. Immunohistochemical staining showed that CD34-positive was 81.5%, vimentin (100.0%), CD99 (100.0%) and bcl-2 (96.3%), as well as negative CK (100.0%) and S-100 (96.3%).

CONCLUSIONThe location of SFT is varying. Though its clinical manifestations vary, the diagnosis is depended on pathology and immunohistochemistry. There are certain specific features related to SFTs on CT or MRI. These imaging techniques may serve to provide helpful information as to the location and vicinal anatomic structure of the tumor, which is of substantial importance for planning surgery.

12E7 Antigen ; Abdominal Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Adult ; Aged ; Antigens, CD ; metabolism ; Antigens, CD34 ; metabolism ; Cell Adhesion Molecules ; metabolism ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pelvic Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Retrospective Studies ; Solitary Fibrous Tumor, Pleural ; diagnosis ; metabolism ; pathology ; surgery ; Solitary Fibrous Tumors ; diagnosis ; metabolism ; pathology ; surgery ; Tomography, Spiral Computed ; Vimentin ; metabolism ; Young Adult

OBJECTIVEThe aim of this study was to evaluate the value of diffusion weighted imaging (DWI) in the diagnosis of patients with breast diseases.

METHODSFifty-three consecutive patients were scanned with GE signa HDx 1.5 T magnetic resonance system equipped with 8-channel breast coil. DWI was scanned by SE-EPI sequence in b values of 500 s/mm(2) and 800 s/mm(2), respectively. The apparent diffusion coefficients (ADC) of these lesions were measured. The mean apparent diffusion coefficients (ADC) of these lesions were calculated in b values of 500 s/mm(2) and 800 s/mm(2), respectively. These lesions' ADC value (rADC) was counted respectively and the result of the rADC was equal to the lesion's ADC divided by the ADC of the ipsilateral normal breast tissue. Threshold of ADC and rADC for differential diagnosis was acquired by ROC (receiver operating characteristic curve) analysis. Different imaging technologies were evaluated emphasizing their sensitivity, specificity and accuracy.

RESULTSSixty-six lesions of 53 cases were confirmed by pathology, including 39 malignant lesions and 27 benign lesions. (1) b = 500 s/mm(2), the threshold of ADC value was 1.435 x 10(-3) mm(2)/s, with a sensitivity of 82.1% and a specificity of 81.5%. The threshold of rADC value was 0.62, with a sensitivity of 76.9% and a specificity of 100%. (2) b = 800 s/mm(2), the threshold of ADC value was 1.295 x 10(-3) mm(2)/s, with a sensitivity of 79.5% and a specificity of 81.5%. The threshold of rADC value was 0.71, with a sensitivity of 89.7% and specificity of 88.9%. (3) The area under the ROC curve was increased for the four diagnostic indicators (ADC(500), ADC(800), rADC(500), rADC(800)).

CONCLUSIONDWI spends short time, and it doesn't need contrast material. ADC value and rADC value have a high sensitivity and specificity as a diagnostic indicator. DWI is helpful in improving the specificity of MR and may become one of valuable conventional procedures for breast tumor diagnosis.

Adult ; Breast ; pathology ; Breast Neoplasms ; diagnosis ; pathology ; Carcinoma, Ductal, Breast ; diagnosis ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; diagnosis ; pathology ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging ; methods ; Female ; Fibroadenoma ; diagnosis ; pathology ; Fibrocystic Breast Disease ; diagnosis ; pathology ; Humans ; Middle Aged ; ROC Curve ; Sensitivity and Specificity