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The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report an in-depth multi-organ proteomic landscape of COVID-19 patient autopsy samples. By integrative analysis of proteomes of seven organs, namely lung, spleen, liver, heart, kidney, thyroid and testis, we characterized 11,394 proteins, in which 5336 were perturbed in COVID-19 patients compared to controls. Our data showed that CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. Dysregulation of protein translation, glucose metabolism, fatty acid metabolism was detected in multiple organs. Our data suggested upon SARS-CoV-2 infection, hyperinflammation might be triggered which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart and thyroid. Evidence for testicular injuries included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. In summary, this study depicts the multi-organ proteomic landscape of COVID-19 autopsies, and uncovered dysregulated proteins and biological processes, offering novel therapeutic clues. HIGHLIGHTSO_LICharacterization of 5336 regulated proteins out of 11,394 quantified proteins in the lung, spleen, liver, kidney, heart, thyroid and testis autopsies from 19 patients died from COVID-19. C_LIO_LICTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. C_LIO_LIEvidence for suppression of glucose metabolism in the spleen, liver and kidney; suppression of fatty acid metabolism in the kidney; enhanced fatty acid metabolism in the lung, spleen, liver, heart and thyroid from COVID-19 patients; enhanced protein translation initiation in the lung, liver, renal medulla and thyroid. C_LIO_LITentative model for multi-organ injuries in patients died from COVID-19: SARS-CoV-2 infection triggers hyperinflammatory which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart, kidney and thyroid. C_LIO_LITesticular injuries in COVID-19 patients included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. C_LI
RESUMO
<p><b>OBJECTIVE</b>To observe the clinical features of Langerhans cell histiocytosis (LCH), and to improve its early diagnosis and treatment.</p><p><b>METHODS</b>Retrospective analysis of 160 cases of adult LCH from pathology department, West China Hospital of Sichuan University and Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 1992 to December 2013 were performed, and their clinical features were analyzed.</p><p><b>RESULTS</b>Of 160 cases, there were 110 male and 50 female, the male to female ratio was 2.2:1. The mean age was 35(18-73) years. There were total 222 lesion sites, including 172(77.5%) osteal lesions, followed by 13(5.8%) lymph nodes and 8(3.6%) oral cavity lesions. The other involved organs were skin(5, 2.2%), liver(5, 2.2%), fossa orbitalis(4, 1.8%), lungs(4, 1.8%), sternoclavicular joint(3, 1.4%), gastrointestinal(2, 0.9%), ear(2, 0.9%), and thyroid (2, 0.9%), adrenal gland (1, 0.5%) and sublingual gland (1, 0.5%). Of 160 cases, 150 (93.8%) had one organ involved while 10 (6.2%) had two or more organs involved. Clinically, 77 cases (48.1%) were misdiagnosed as bone tumors (28 cases, including giant cell tumor, fibrous dysplasia, chondroblastoma, osteoblastoma and osteosarcoma), bone tuberculosis (13 cases), meningioma(9 cases), bone cysts (5 cases), chronic osteomyelitis (5 cases) and diabetes insipidus (5 cases) , skin (4 cases) diseases malignant lymphoma (4 cases), chronic skin ulcers (4 cases), chronic otitis media (1 case), lung (1 case) and oral cancer (1 case).</p><p><b>CONCLUSION</b>In this group of the adult cases, the ratio of the male patients is higher. Adult LCH occurs predominantly in bone and presents mainly as unisystem single-focal disease, but multi-organ lesion and skin involvement are lower than that reported in the literatures. Just as LCH in children, adult LCH is also easy to be misdiagnosed. We should raise awareness of the disease and pathological examination is helpful for early diagnosis.</p>