Trimethylamine N-Oxide Promotes Autoimmunity and a Loss of Vascular Function in Toll-like Receptor 7-Driven Lupus Mice

Plasma levels of trimethylamine N-oxide (TMAO) are elevated in lupus patients. We analyzed the implication of TMAO in autoimmunity and vascular dysfunction of the murine model of systemic lupus erythematosus (SLE) induced by the activation of the Toll-like receptor (TLR)7 with imiquimod (IMQ). Female BALB/c mice were randomly divided into four groups: untreated control mice, control mice treated with the trimethylamine lyase inhibitor 3,3-dimethyl-1-butanol (DMB), IMQ mice, and IMQ mice treated with DMB. The DMB-treated groups were administered the substance in their drinking water for 8 weeks. Treatment with DMB reduced plasma levels of TMAO in mice with IMQ-induced lupus. DMB prevents the development of hypertension, reduces disease progression (plasma levels of anti-dsDNA autoantibodies, splenomegaly, and proteinuria), reduces polarization of T lymphocytes towards Th17/Th1 in secondary lymph organs, and improves endothelial function in mice with IMQ-induced lupus. The deleterious vascular effects caused by TMAO appear to be associated with an increase in vascular oxidative stress generated by increased NADPH oxidase activity, derived in part from the vascular infiltration of Th17/Th1 lymphocytes, and reduced nrf2-driven antioxidant defense. In conclusion, our findings identified the bacterial-derived TMAO as a regulator of immune system, allowing for the development of autoimmunity and endothelial dysfunction in SLE mice.

Cerebral Infarction Secondary to Vascular Infiltration of Glioblastoma Confirmed in High-Resolution Vessel Wall MRI

Acute cerebral infarction secondary to glioblastoma is rarely reported, and its mechanism is still controversial. Vascular infiltration of malignant cell, direct mass effect and local procoagulant effect were considered as main pathophysiology. We report a case of glioblastoma-related cerebral infarction documented by high resolution vessel wall magnetic resonance imaging, which reveals concentric enhancement of arterial wall and intraluminal thrombus without direct compression. These findings suggest tumor cell infiltration of intracranial vessels is one of the important mechanisms of glioblastoma-related cerebral infarction.

pT1 Colorectal Cancer Detected in a Colorectal Cancer Mass Screening Program: Treatment and Factors Associated with Residual and Extraluminal Disease

The aim of this study is to describe the treatment of pT1 colorectal cancer (CRC) in a mass screening program, the surgery-related complications and the factors associated with residual disease after endoscopic resection and extraluminal disease after surgery. We included in this retrospective analysis all the pT1 CRC detected in the Galician CRC screening program between May 2013 and June 2019. We determined which variables were independently associated with the outcomes of the study through a multivariable logistic regression analysis. We included 370–354 pT1 N0(X), 16 pT1N1- out of the 971 CRC detected; 277 (74.9%) were resected endoscopically and 162 (43.8%) were not referred to surgery. There were surgical complications in 30.7% and 16.3% of the patients during hospitalization and after discharge. Residual disease was detected in 12 (4.3%) after endoscopic resection and extraluminal disease in 18 (8.6%) patients after surgery. The variables independently associated with initial endoscopic resection were a pedunculated morphology (OR 33.1, 95% CI 4.3–254), a diameter ≥ 20 mm (OR 3.94, 95% CI 1.39–11.18) and a Site–Morphology–Size–Access score < 9 (OR 428, 95% CI 42–4263). The variables related with surgery rescue were a piecemeal resection (OR 4.48, 95% CI 1.48–13.6), an infiltrated/nonevaluable resection border (OR 7.44, 95% CI 2.12–26.0), a non-well-differentiated histology (OR 4.76, 95% CI 1.07–20.0), vascular infiltration (OR 8.24, 95% CI 2.72–25.0) and a Haggitt 4 infiltration of the submucosa (OR 5.68, 95% CI 2.62–12.3). Residual disease after endoscopic resection was associated with an infiltrated/nonevaluable resection border (OR 34.9, 95% CI 4.08–298), a non-well-differentiated histology (OR 6.67, 95% CI 1.05–50.0), and the vascular infiltration of the submucosa (OR 7.61, 95% CI 1.55–37.4). The variables related with extraluminal disease after surgical resection were no endoscopic resection (OR 4.34, 95% CI 1.26–14.28), a non-well-differentiated histology (OR 4.35, 95% CI 1.39–14.29) and the lymphatic infiltration of the submucosa (OR 4.8, 95% CI 1.32–17.8). In a CRC screening program, although most of pT1 CRC are candidates for endoscopic treatment, surgery is a safe procedure. We have defined some easy to evaluate variables that can be used in the decision-making process.

What are the Survival Factors in Surgically Resected Synchronous Multiple Primary Lung Cancers: A Retrospective Study

Background: With the popularization of high-resolution computed tomography (HRCT), the detection rate of synchronous multiple primary lung cancer (SMPLC) is increasing. We retrospectively analyzed the surgical results of SMPLC patients in our hospital to determine the best treatment for SMPLC.Methods: A total of 90 SMPLC patients met the diagnostic criteria underwent complete resection and lymph node dissection or sampling without any preoperative induction therapy in the Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University. We analyzed the postoperative survival rate, and further studied the relationship between survival rates and sex, age, preoperative symptoms, tumor location, tumor number, tumor size, surgical type, surgical frequency, histopathologic types, vascular infiltration, visceral pleural invasion and postoperative therapy.Results: Among 90 patients, the 1- and 3-year disease free survival (DFS) rates were 97.0% and 76.7% while the 1- and 3-year overall survival (OS) rates were 98.81% and 82.35%. Vascular infiltration (HR=402.46, p=0.005) and postoperative chemotherapy (HR>1000, p<0.001) were independent risk factors for DFS, while only postoperative chemotherapy (HR=184.10, p=0.002) was an independent risk factor for OS.Conclusions: First, SMPLC is different from intrapulmonary metastasis and its clinical stage is also different from the 8th (2015) edition TNM classification for lung cancer. Second, when pulmonary function permits, surgery (complete resection and lymph node dissection) is a significantly beneficial treatment for patients with SMPLC. Third, for early stage SMPLC patients, vascular infiltration and postoperative chemotherapy are harmful to the survival.

Comparison of clinicopathological characteristics of endogenous and exogenous cervical cancer with its clinical significance

<p class="abstract"><strong><span lang="EN-US">Background: </span></strong>Cervical cancer is the third leading cause of cancer death in women of less developed countries due to poor screening and decreased diagnostic approaches. We aimed to investigate and differentiate the distinct clinicopathological characteristics and prevalence of endogenous and exogenous cervical in hospitalized patients<span lang="EN-US">.</span></p><p class="abstract"><strong><span lang="EN-US">Methods: </span></strong>A study was performed contained 663 patients that were enrolled and underwent for screening of endogenous and exogenous cervical cancer in Qilu Hospital of Shandong University, from January 2010 to March 2015. </p><p class="abstract"><strong><span lang="EN-US">Results: </span></strong>Our results indicated that combined examination of thin-prep liquid-based cytology test and human papillomavirus (HPV)-DNA are effective for diagnosis of endogenous and exogenous cervical cancer. The clinicopathological characteristics based on tumor growth pattern, and high risk HPV-DNA incidence had no significant difference (p&gt;0.05) in endogenous and exogenous cervical cancer patients. The higher ratio of lymph node metastasis in endogenous cervical cancer and exogenous cervical cancer during IB1-stage (24.3% vs 12.9%), and in IIA2-stage (36.4% vs 25%) was observed respectively. In addition, our data provide compelling evidence that the level of deep interstitial infiltration, and lymphatic vascular infiltration in endogenous cervical cancer was collectively higher (82.7% and 33%) compared to exogenous cervical cancer (62.4% and 18.3%) respectively during all stages<span lang="EN-US">.</span></p><p class="abstract"><strong><span lang="EN-US">Conclusions: </span></strong>The higher percentage of lymph node metastasis,<strong> </strong>deep interstitial infiltration, and lymphatic vascular infiltration was observed in endogenous cervical cancer which might be the biomarker and differential key points for the diagnosis of endogenous cervical cancer. Taken together, our study provides clinicopathological features to diagnose, and differentiate the endogenous and exogenous type cervical cancer with its prevalence.</p>

Design and biofabrication of dermal regeneration scaffolds: role of oligomeric collagen fibril density and architecture

Aim: To evaluate dermal regeneration scaffolds custom-fabricated from fibril-forming oligomeric collagen where the total content and spatial gradient of collagen fibrils was specified. Materials & methods: Microstructural and mechanical features were verified by electron microscopy and tensile testing. The ability of dermal scaffolds to induce regeneration of rat full-thickness skin wounds was determined and compared with no fill control, autograft skin and a commercial collagen dressing. Results: Increasing fibril content of oligomer scaffolds inhibited wound contraction and decreased myofibroblast marker expression. Cellular and vascular infiltration of scaffolds over the 14-day period varied with the graded density and orientation of fibrils. Conclusion: Fibril content, spatial gradient and orientation are important collagen scaffold design considerations for promoting vascularization and dermal regeneration while reducing wound contraction.