Real-world applications of the new grading system in lung adenocarcinoma: A study of 907 patients focusing on revealing the relationship between pathologic grade and genetic status.

BACKGROUND: The status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be elucidated. METHODS: We included patients with invasive non-mucinous LUAD, evaluated their differentiation, and collected available clinicopathological information, gene mutations, and analyzed clinical outcomes. RESULTS: Among the 907 patients with invasive non-mucinous LUAD, 321 (35.4 %) were poorly differentiated, 422 (46.5 %) were moderately differentiated, and 164 (18.1 %) were well differentiated. EGFR mutation was more common in the LUADs accompanied without CGP (complex glandular pattern) than LUADs with CGP (p < 0.001). Correlation analysis between mutations and clinical characteristics showed that EGFR gene mutation (p < 0.001), KRAS gene mutation (p < 0.05), and ALK gene rearrangement (p < 0.001) were significantly related to the degree of tumor differentiation, and the KRAS and ALK gene mutation frequencies were higher in the low-differentiation group than in the high and medium differentiation groups. The EGFR mutation frequency was higher in the well/moderately differentiated adenocarcinoma group. CONCLUSIONS: Our study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.

Yolk Sac Tumor Originating From Cervical Adenocarcinoma: A Case Predominated by Enteroblastic Differentiation.

The fetal gut-like phenotype can be found in yolk sac tumors and adenocarcinomas with enteroblastic differentiation (AEBDs). We report a cervical yolk sac tumor in a 44-yr-old woman. The tumor has similar morphology, immunophenotype, and molecular features to the AEBD of the digestive system. The tumor showed a glandular-predominant growth pattern, composed of columnar cells with clear glycogen-rich cytoplasm. The microcystic/reticular architecture or Schiller-Duval bodies were not found in the tumor. Immunohistochemically, the tumor cells were positive for p16, glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), CDX-2, and p53. TP53 mutation was identified by next-generation sequencing, and human papillomavirus (HPV) 35 was detected by HPV DNA polymerase chain reaction. In the present case, the adenocarcinoma cells in the superficial cervical glandular epithelium and the nonclear glandular components proved the existence of somatic components. The positivity of p16 and HPV also supports that the present case originates from an HPV-associated adenocarcinoma. The yolk sac tumor should be thought of as "germ cell differentiation" from a somatic carcinoma. This kind of yolk sac tumor arising from somatic-type adenocarcinoma in the female genital tract may be the counterpart of AEBD in the digestive tracts and adenocarcinomas with fetal gut-like morphology in other organs. The tumor might be more aggressive than conventional adenocarcinoma, pathologists should highlight the existence of the enteroblastic component in the pathologic report.

Neurogenic orthostatic hypotension with Parkinson's disease as a cause of syncope: A case report.

BACKGROUND: Syncope presents with diagnostic challenges and is associated with high healthcare costs. Neurogenic orthostatic hypotension (nOH) as one cause of syncope is not well established. We review a case of syncope caused by nOH in a patient with Parkinson's disease. CASE SUMMARY: We describe a case of syncope caused by nOH in Parkinson's disease and review the literature. A 70-year-old man with Parkinson's disease had uncontrolled blood pressure for 1 mo, with blood pressure ranging from 70/40 to 220/112 mmHg, and once lost consciousness lasting for several minutes after getting up. Ambulatory blood pressure monitoring indicated nocturnal hypertension (up to 217/110 mmHg) and morning orthostatic hypotension (as low as 73/45 mmHg). Seated-to-standing blood pressure measurement showed that the blood pressure dropped from 173/96 mmHg to 95/68 mmHg after standing for 3 min from supine position. A diagnosis of nOH with supine hypertension was made. During the course of treatment, Midodrine could not improve the symptoms. Finally, the patient's blood pressure stabilized with simple strategies by strengthening exercises, reducing the duration of lying in bed in the daytime, and consuming water intake before getting up. CONCLUSION: nOH is one of the causes of syncope. Ambulatory blood pressure monitoring is a cost-effective method for its diagnosis, and non-pharmacological measures are still the primary management methods.

Comparison of adipose­ and bone marrow­derived stem cells in protecting against ox­LDL­induced inflammation in M1­macrophage­derived foam cells.

Adipose­derived stem cells (ADSCs) and bone marrow­derived stem cells (BMSCs) are considered to be prospective sources of mesenchymal stromal cells (MSCs), that can be used in cell therapy for atherosclerosis. The present study investigated whether ADSCs co­cultured with M1 foam macrophages via treatment with oxidized low­density lipoprotein (ox­LDL) would lead to similar or improved anti­inflammatory effects compared with BMSCs. ADSCs, peripheral blood monocytes, BMSCs and ox­LDL were isolated from ten coronary heart disease (CHD) patients. After three passages, the supernatants of the ADSCs and BMSCs were collected and systematically analysed by liquid chromatography­quadrupole time­of­flight­mass spectrometry (6530; Agilent Technologies, Inc., Santa Clara, CA, USA). Cis­9, trans­11 was deemed to be responsible for the potential differences in the metabolic characteristics of ADSCs and BMSCs. These peripheral blood monocytes were characterized using flow cytometry. Following peripheral blood monocytes differentiation into M1 macrophages, the formation of M1 foam macrophages was achieved through treatment with ox­LDL. Overall, 2x106 ADSCs, BMSCs or BMSCs+cis­9, trans­11 were co­cultured with M1 foam macrophages. Anti­inflammatory capability, phagocytic activity, anti­apoptotic capability and cell viability assays were compared among these groups. It was demonstrated that the accumulation of lipid droplets decreased following ADSCs, BMSCs or BMSCs+cis­9, trans­11 treatment in M1 macrophages derived from foam cells. Consistently, ADSCs exhibited great advantageous anti­inflammatory capabilities, phagocytic activity, anti­apoptotic capability activity and cell viability over BMSCs or BMSCs+cis­9, trans­11. Additionally, BMSCs+cis­9, trans­11 also demonstrated marked improvement in anti­inflammatory capability, phagocytic activity, anti­apoptotic capability activity and cell viability in comparison with BMSCs. The present results indicated that ADSCs would be more appropriate for transplantation to treat atherosclerosis than BMSCs alone or BMSCs+cis­9, trans­11. This may be an important mechanism to regulate macrophage immune function.