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Postoperative Issues Anticipate Long-term Final result Soon after Healing Resection for Punctured Digestive tract Cancer.
Although peripheral artery disease (PAD) is a major health problem, there have been limited advances in medical therapies. In PAD patients, angiogenesis is regarded as a promising therapeutic strategy to promote new arterial vessels and improve perfusion of ischemic tissue. Autophagy plays a critical role in catabolic processes for cell survival under normal and stressful conditions and plays fundamental biological roles in various cellular functions. In the present study, we showed that autophagy in endothelial cells is important for the repair and regeneration of damaged tissues. In a hindlimb ischemia mouse model, autophagy was stimulated in endothelial cells of the quadriceps muscle, and adjacent cells proliferated and regenerated. The autophagy pathway was induced under prolonged hypoxia in endothelial cells, and autophagy increased angiogenic activities. Moreover, conditioned media from endothelial cells blocked autophagy and inhibited the proliferation of muscle cells, suggesting that autophagic stimulation in endothelial cells affects the survival of adjacent cells, such as muscle. Collectively, hypoxia/ischemia-induced autophagy angiogenesis, and the damaged tissue surrounded by neo-vessels was regenerated in an ischemia model. Therefore, we strongly suggest that stimulation of autophagy in endothelial cells may be a potent therapeutic strategy in severe vascular diseases, including PAD.Colorectal cancer (CRC) is a common malignant tumor with a poor prognosis. However, its pathogenesis has not been fully elucidated, accounting for poor overall survival. Circular RNA (circRNA) is a class of noncoding RNAs discovered many years ago. Only recently have they been re-evaluated for their important roles in the regulation of gene expression. Studies have confirmed that circRNAs have important biological functions in a variety of malignant tumors. This study aimed to characterize one circRNA derived from the MBOAT2 gene and termed it circMBOAT2, which has been reported to promote prostate cancer progression. CircMBOAT2 is highly expressed in both CRC tissues and serum samples, and has a correlation with tumor stage. The receiver-operating characteristic curves suggested that circMBOAT2 acted as a novel diagnostic tumor marker in CRC. Univariate and multivariate analyses showed that the levels of circMBOAT2 in tissues were independent prognostic markers of CRC. Further functional studies revealed that circMBOAT2 served as a microRNA (miRNA) sponge of miR-519d-3p and promoted the proliferation, migration, and invasion of CRC cells. Also, circMBOAT2 regulated cell proliferation and migration by competitively binding to miR-519d-3p and targeting troponin-associated protein (TROAP) in CRC cells. These results suggested that circMBOAT2 might be a novel potential biomarker of CRC.The global Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has affected more than eight million people. There is an urgent need to investigate how the adaptive immunity is established in COVID-19 patients. In this study, we profiled adaptive immune cells of PBMCs from recovered COVID-19 patients with varying disease severity using single-cell RNA and TCR/BCR V(D)J sequencing. The sequencing data revealed SARS-CoV-2-specific shuffling of adaptive immune repertories and COVID-19-induced remodeling of peripheral lymphocytes. Characterization of variations in the peripheral T and B cells from the COVID-19 patients revealed a positive correlation of humoral immune response and T-cell immune memory with disease severity. Sequencing and functional data revealed SARS-CoV-2-specific T-cell immune memory in the convalescent COVID-19 patients. Furthermore, we also identified novel antigens that are responsive in the convalescent patients. Altogether, our study reveals adaptive immune repertories underlying pathogenesis and recovery in severe versus mild COVID-19 patients, providing valuable information for potential vaccine and therapeutic development against SARS-CoV-2 infection.Patients with colorectal cancer (CRC) often develop malignant regrowth of metastatic dormant tumor cells in liver years after primary treatment. FBX8 is involved in suppressing tumor metastasis. Short-term chemotherapy experiments and liver metastasis mice model of orthotopic injection into the cecum were performed to construct the dormant models. GST-pull-down assay, Co-IP and immunofluorescence were used to confirm the bindings among FBX8 and its substrates. FBX8 upregulated the expression of epithelial and stemness markers, while downregulated the expression of mesenchymal and proliferative markers associated with tumor cell dormancy. FBX8 promoted the maintenance of metastatic dormancy of CRC cells. Mechanistically, FBX8 directly bound to HIF-1α, CDK4 and C-myc through its Sec7 domain and led to the ubiquitin degradation of these proteins, thereby inhibiting cell cycle progression, proliferation, angiogenesis, and metastasis. Clinically, FBX8 expression was negatively correlated with the HIF-1α, CDK4, and c-Myc in CRC tissues. Our study reveals a novel mechanism of FBX8 in regulating tumor metastatic dormancy in liver and provides new strategies for the treatment of CRC metastasis.Apoptotic cell clearance by phagocytes is a fundamental process during development, homeostasis and the resolution of inflammation. However, the demands placed on phagocytic cells such as macrophages by this process, and the limitations these interactions impose on subsequent cellular behaviours are not yet clear. Here, we seek to understand how apoptotic cells affect macrophage function in the context of a genetically tractable Drosophila model in which macrophages encounter excessive amounts of apoptotic cells. Loss of the glial-specific transcription factor Repo prevents glia from contributing to apoptotic cell clearance in the developing embryo. We show that this leads to the challenge of macrophages with large numbers of apoptotic cells in vivo. As a consequence, macrophages become highly vacuolated with cleared apoptotic cells, and their developmental dispersal and migration is perturbed. We also show that the requirement to deal with excess apoptosis caused by a loss of repo function leads to impaired inflammatory responses to injury. However, in contrast to migratory phenotypes, defects in wound responses cannot be rescued by preventing apoptosis from occurring within a repo mutant background. In investigating the underlying cause of these impaired inflammatory responses, we demonstrate that wound-induced calcium waves propagate into surrounding tissues, including neurons and glia of the ventral nerve cord, which exhibit striking calcium waves on wounding, revealing a previously unanticipated contribution of these cells during responses to injury. Taken together, these results demonstrate important insights into macrophage biology and how repo mutants can be used to study macrophage-apoptotic cell interactions in the fly embryo. Furthermore, this work shows how these multipurpose cells can be 'overtasked' to the detriment of their other functions, alongside providing new insights into which cells govern macrophage responses to injury in vivo.Abnormal lipid/lipoprotein metabolism induced by obesity may affect spermatogenesis by inhibiting testosterone synthesis in Leydig cells. It is crucial to determine which components of lipoproteins inhibit testosterone synthesis. Circulating oxidized low-density lipoprotein (oxLDL), the oxidized form of LDL, has been reported to be an independent risk factor for decreased serum testosterone levels. However, whether oxLDL has a damaging effect on Leydig cell function and the detailed mechanisms have been rarely studied. This study first showed the specific localization of oxLDL and mitochondrial structural damage in testicular Leydig cells of high-fat diet-fed mice in vivo. We also found that oxLDL reduced the mitochondrial membrane potential (MMP) by disrupting electron transport chain and inhibited testosterone synthesis-related proteins and enzymes (StAR, P450scc, and 3β‑HSD), which ultimately led to mitochondrial dysfunction and decreased testosterone synthesis in Leydig cells. Further experiments demonstrated that oxLDL promoted lipid uptake and mitochondrial dysfunction by inducing CD36 transcription. Meanwhile, oxLDL facilitated COX2 expression through the p38 MAPK signaling pathway in Leydig cells. Blockade of COX-2 attenuated the oxLDL-induced decrease in StAR and P450scc. Our clinical results clarified that the increased serum oxLDL level was associated with a decline in circulating testosterone levels. Our findings amplify the damaging effects of oxLDL and provide the first evidence that oxLDL is a novel metabolic biomarker of male-acquired hypogonadism caused by abnormal lipid metabolism.BACKGROUND This population study aimed to investigate the demographic and clinical characteristics and outcome of cases of coronavirus disease 2019 in Lu'an City, China between January 22, 2020 and February 18, 2020 identified from the China Information System for Disease Control and Prevention (CISDCP). MATERIAL AND METHODS Laboratory-confirmed cases of COVID-19 reported in the CISDCP were included in this study. The distribution of cases, exposure history, clustered epidemic situation, and clinical manifestations, disease severity, and key time nodes were analyzed. Once the throat swab or sputum sample was positive for SARS-CoV-2 by real-time reverse transcriptase-polymerase chain reaction testing as confirmed cases. RESULTS There were 69 cases of COVID-19 that were confirmed between January 22 and February 18, 2020 reported. The onset time was concentrated on January 25, 2020 solstice to February 6, 2020 (71.0%), and the reporting dates were concentrated on January 31, 2020 and February 9, 2020 (69.6%). Nineteen cases (27.5%) had a history of sojourn in Hubei Province, and none of the cases reported after February 6, 2020 had a history of exposure in Hubei Province. There were 14 cluster outbreaks, and human-to-human transmission was the most common (78.6%). The most common symptoms were fever (56.5%), cough (37.7%), and self-conscious discomfort (14.5%). Besides, there were 9 severe cases (13.0%). CONCLUSIONS The epidemic prevention and control in Lu'an City has achieved phased results. Yet, new strict control measures need to be implemented to prevent a further outbreak, especially for those who will return to Lu'an City.BACKGROUND The effect of corticosteroids in the management of patients with coronavirus disease 2019 (COVID-19) is unclear. CASE REPORT A 67-year-old man who tested positive for COVID-19 by reverse-transcription PCR (RT-PCR) analysis was admitted to our hospital. On admission, he had no dyspnea and his oxygen saturation (SpO₂) level was normal. Chest imaging revealed ground-glass opacities (GGO) distributed in both lung fields. Four days after admission, bilateral lung shadows worsened, with a slight reduction in SpO₂ levels. Short-term corticosteroid therapy was initiated, and SpO₂ and radiographic findings promptly improved without use of antiviral agents. CONCLUSIONS More data are required to ascertain the role of corticosteroids in the management of COVID-19 pneumonia.
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