This study was to determine age-specific impact of fertility preserving surgery on disease-specific survival in women with stage I borderline ovarian tumors (BOTs). Patients diagnosed during ...1988-2000 were selected from The Surveillance, Epidemiology, and End Results (SEER) database. The age-specific impact of fertility preserving surgery and other risk factors were analyzed in patients with stage I BOTs using Cox proportion hazard regression models. Data from our hospital were collected during 1996-2017 to determine the prevalence of patients who had undergone fertility preserving surgery.
Of a total 6295 patients in the SEER database, this study selected 2946 patients with stage T1 BOTs who underwent fertility preserving or radical surgery. Their median age at diagnosis was 45.0 years and the median follow-up time was 200 months. Fertility preserving surgery was performed in 1000/1751 (57.1%) patients < 50 years and in 1,81/1195 (15.1%) patients ≥50 years. Fertility preserving surgery was significantly associated with worse disease-specific survival only in patients ≥50 years. Increased age, stage T1c and mucinous histology were risk factors for overall patients or patients ≥50 years, but not for < 50 years. Data from our hospital showed that fertility preserving surgery was performed in 53.9 and 12.3%patients < 50 and ≥ 50 years with stage I disease, respectively.
Fertility preserving surgery is safe for women < 50 years with early staged BOTs, but it may decrease disease-specific survival in patients ≥50 years. Conservative surgery is performed at a relatively high rate in patients ≥50 years.
CCN4 regulates vascular smooth muscle cell migration and proliferation Liu, H., Nanfang Hospital, Southern Medical University, Guangzhou, China; Dong, W.P., Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China; Lin, Z.Q., Nanfang Hospital, Southern Medical University, Guangzhou, China ...
Molecules and cells,
08/2013, Volume:
36, Issue:
2
Journal Article
Peer reviewed
Open access
The migration and proliferation of vascular smooth muscle cells (VSMCs) are essential elements during the development of atherosclerosis and restenosis. An increasing number of studies have reported ...that extracellular matrix (ECM) proteins, including the CCN protein family, play a significant role in VSMC migration and proliferation. CCN4 is a member of the CCN protein family, which controls cell development and survival in multiple systems of the body. Here, we sought to determine whether CCN4 is involved in VSMC migration and proliferation. We examined the effect of CCN4 using rat cultured VSMCs. In cultured VSMCs, CCN4 stimulated the adhesion and migration of VSMCs in a dose-dependent manner, and this effect was blocked by an antibody for integrin α5β1. CCN4 expression was enhanced by the pro-inflammatory cytokine tumor necrosis factor α (TNF-α). Furthermore, knockdown of CCN4 by siRNA significantly inhibited the VSMC proliferation. CCN4 also could up-regulate the expression level of marker proteins of the VSMCs phenotype. Taken together, these results suggest that CCN4 is involved in the migration and proliferation of VSMCs. Inhibition of CCN4 may provide a promising strategy for the prevention of restenosis after vascular interventions.
The NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome activation plays a critical role in innate immune and pathogenic microorganism ...infections. However, excessive activation of NLRP3 inflammasome will lead to cellular inflammation and tissue damage, and naturally it must be precisely controlled in the host. Here, we discovered that solute carrier family 25 member 3 (SLC25A3), a mitochondrial phosphate carrier protein, plays an important role in negatively regulating NLRP3 inflammasome activation. We found that SLC25A3 could interact with NLRP3, overexpression of SLC25A3 and knockdown of SLC25A3 could regulate NLRP3 inflammasome activation, and the interaction of NLRP3 and SLC25A3 is significantly boosted in the mitochondria when the NLRP3 inflammasome is activated. Our detailed investigation demonstrated that the interaction between NLRP3 and SLC25A3 disrupted the interaction of NLRP3-NEK7, promoted ubiquitination of NLRP3, and negatively regulated NLRP3 inflammasome activation. Thus, these findings uncovered a new regulatory mechanism of NLRP3 inflammasome activation, which provides a new perspective for the therapy of NLRP3 inflammasome-associated inflammatory diseases.
Discrimination of high-risk types of human papillomaviruses plays an important role in the diagnosis and remedy of cervical cancer. Recently, several computational methods have been proposed based on ...protein sequence-based and structure-based information, but the information of their related proteins has not been used until now. In this paper, we proposed using protein “sequence space” to explore this information and used it to predict high-risk types of HPVs. The proposed method was tested on 68 samples with known HPV types and 4 samples without HPV types and further compared with the available approaches. The results show that the proposed method achieved the best performance among all the evaluated methods with accuracy 95.59% and F1-score 90.91%, which indicates that protein “sequence space” could potentially be used to improve prediction of high-risk types of HPVs.
We aimed to develop and validate a radiomics nomogram for preoperative prediction of microvascular invasion (MVI) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
A total of 304 ...eligible patients with HCC were randomly divided into training (n=184) and independent validation (n=120) cohorts. Portal venous and arterial phase computed tomography data of the HCCs were collected to extract radiomic features. Using the least absolute shrinkage and selection operator algorithm, the training set was processed to reduce data dimensions, feature selection, and construction of a radiomics signature. Then, a prediction model including the radiomics signature, radiologic features, and alpha-fetoprotein (AFP) level, as presented in a radiomics nomogram, was developed using multivariable logistic regression analysis. The radiomics nomogram was analyzed based on its discrimination ability, calibration, and clinical usefulness. Internal cohort data were validated using the radiomics nomogram.
The radiomics signature was significantly associated with MVI status (P < 0.001, both cohorts). Predictors, including the radiomics signature, nonsmooth tumor margin, hypoattenuating halos, internal arteries, and alpha-fetoprotein level were reserved in the individualized prediction nomogram. The model exhibited good calibration and discrimination in the training and validation cohorts (C-index 95% confidence interval: 0.846 0.787-0.905 and 0.844 0.774-0.915, respectively). Its clinical usefulness was confirmed using a decision curve analysis.
The radiomics nomogram, as a noninvasive preoperative prediction method, shows a favorable predictive accuracy for MVI status in patients with HBV-related HCC.
Glucose metabolism and innate immunity evolved side-by-side. It is unclear if and how the two systems interact with each other during hepatitis B virus (HBV) infections and, if so, which mechanisms ...are involved. Here, we report that HBV activates glycolysis to impede retinoic acid-inducible gene I (RIG-I)-induced interferon production. We demonstrate that HBV sequesters MAVS from RIG-I by forming a ternary complex including hexokinase (HK). Using a series of pharmacological and genetic approaches, we provide in vitro and in vivo evidence indicating that HBV suppresses RLR signaling via lactate dehydrogenase-A-dependent lactate production. Lactate directly binds MAVS preventing its aggregation and mitochondrial localization during HBV infection. Therefore, we show that HK2 and glycolysis-derived lactate have important functions in the immune escape of HBV and that energy metabolism regulates innate immunity during HBV infection.
A major challenge for effective application of CRISPR systems is to accurately predict the single guide RNA (sgRNA) on-target knockout efficacy and off-target profile, which would facilitate the ...optimized design of sgRNAs with high sensitivity and specificity. Here we present DeepCRISPR, a comprehensive computational platform to unify sgRNA on-target and off-target site prediction into one framework with deep learning, surpassing available state-of-the-art in silico tools. In addition, DeepCRISPR fully automates the identification of sequence and epigenetic features that may affect sgRNA knockout efficacy in a data-driven manner. DeepCRISPR is available at http://www.deepcrispr.net/ .
Abstract Purpose We aimed to critically analyze the current evidence regarding the role of dynamic supine MRI (dsMRI) in the evaluation of cervical spondylotic myelopathy (CSM). Methods 13 studies ...were identified through a comprehensive literature search performed in the PubMed, EMBASE, and ISI databases as fulfilling the inclusion criteria and were reviewed for subject characteristics, radiographical parameters, and salient findings. Results Studies herein reviewed suggested that dsMRI was able to detect new appearance or increased grade of medullary compression in at least 20% of patients and to demonstrate an average narrowing of the cervical canal by 20% (in comparison to the neutral position). Several additional parameters were investigated but their clinical significance remained unconfirmed. Two studies examined how surgical decision-making could be affected by the additional findings of dsMRI. Conclusions dsMRI represents an available modification of conventional static MRI and is potentially able to demonstrate pathologies that might be previously missed. Evidence suggests that dsMRI can elucidate spinal cord compression with higher sensitivity, resulting in improved diagnostic accuracy of CSM, which may impact surgical planning for these patients. However, more high-quality studies are required to further establish its indications to avoid over-diagnosis with this powerful imaging technique and to justify its cost-effectiveness.
Case report.
To describe a three-dimensional (3D) printed axial vertebral body used in upper cervical spine reconstruction after a C2 Ewing sarcoma resection in an adolescent boy.
Ewing sarcoma is a ...malignant musculoskeletal neoplasm with a peak incidence in adolescents. Cervical spine as the primary site of the tumor has been related to a worse prognosis. Tumor resection is particularly challenging in the atlantoaxial region due to complexity of the anatomy, necessity for extensive resection according to oncological principles, and a lack of specialized implants for reconstruction. 3D printing refers to a process where 3D objects are created through successive layering of material under computer control. Although this technology potentially enables accurate fabrication of patient-specific orthopedic implants, literature on its utilization in this regard is rare.
A 12-year-old boy with a C2 Ewing sarcoma underwent a staged spondylectomy. Wide resection of the posterior elements was first performed. Two weeks later, a high anterior retropharyngeal approach was taken to remove the remains of the C2 vertebra. A customized artificial vertebral body fabricated according to a computer model using titanium alloy powder was inserted to replace the defect between C1 and C3. The microstructure of the implant was optimized for better biomechanical stability and enhanced bone healing.
Patient had an uneventful recovery and began to ambulate on postoperative day 7. Adjuvant treatment commenced 3 weeks after the surgery. He was tumor-free at the 1-year follow-up. Computed tomography studies revealed evidence of implant osseointegration and no subsidence or displacement of the construct.
This is a case example on the concept of personalized precision medicine in a surgical setting and demonstrates how 3D-printed, patient-specific implants may bring individualized solutions to rare problems wherein restoration of the specific anatomy of each patient is a key prognostic factor.
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