ABSTRACT
Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04±0.65 vs. 0.99±0.09, F=30.36, P<0.001), and was closely related to T stage and clinical stage (Ⅰ-Ⅱvs.Ⅲ-Ⅳ: 1.75±0.39 vs. 2.18±0.71, F=2.25, P<0.05; T1-2 vs. T3-4: 1.71±0.42 vs. 2.20±0.69, F=2.06, P<0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P<0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Exosomes , Ferroptosis , Head and Neck Neoplasms , Macrophages , Squamous Cell Carcinoma of Head and NeckABSTRACT
Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.
Subject(s)
Humans , China , Drugs, Chinese Herbal , Hypertension, Pulmonary/drug therapy , Materia Medica , Medicine, Chinese TraditionalABSTRACT
This paper systematically reviews the latest and relevant literatures and policy documents on the in-tegrated health services in Canada in recent years. Therefore, it summarizes the practice and mode of integrated serv-ice delivery in Ontario, Alberta and Quebec wherein the integration among health organization, health service team, and a series of health services are included. The contributing factors and impeding factors ( the barriers) of organiza-tional integration and specific integration strategy were summarized. Finally, according to the actual practical situa-tion, it is proposed that China should adhere to the government-led approach in promoting the integration of health services, and give a full play to the positive role of the market mechanism. Through strengthening the network man-agement and group service of primary health services, emphasis will be put on health services of population groups and specific diseases. Therefore, integration will be regarded as a strategic priority, increasing incentives and boos-ting promotion of nursing personnel on the process of Integrated Service Delivery, building the health information sys-tem that is conducive to integration in order to continuously advance Hierarchical Diagnosis and bridge the fragmented service system. This will help in providing residents with personalized, convenient, comprehensive, and continuous health services.
ABSTRACT
<p><b>OBJECTIVE</b>To compare the functional results of transoral CO2 laser epiglottectomy with transcervical supraglottic laryngectomy and to find the landmarks for CO2 laser surgery.</p><p><b>METHODS</b>Forty-nine preoperatively untreated patients diagnosed as clinical T1-2N0M0 epiglottic carcinomas enrolled from June 1, 2006, to November 1, 2009 in the Second Affiliated Hospital of Harbin Medical University were studied retrospectively. Seventeen cases were treated by CO2 laser whereas 32 by open surgeries. The upper edge of thyroid cartilage and mucosal recess infra epiglottic tubercle could be used as intraoperation landmarks for transoral CO2 laser surgery. Optional neck dissections (II, III) were performed for 34 patients with tumors on laryngeal face, but not for 15 with tumors on the edges of epiglottis or small laryngeal face tumors.</p><p><b>RESULTS</b>The follow-up for this study covers a period ranging from 3 to 6 years postoperatively. Four local recurrences were found for this study, 2 for laser surgery who underwent additional repeated exisions and 2 for conventional techniques, one received radiotherapy (60 Gy) and another with total laryngectomy. The incidence of lymph node metastasis was 10.2% (5/49) in all cases. Time of naso-feeding or hospitalisation was significantly shorter for CO2 laser treated patients than that for open techniques. Overall 3 year's survival rates were 100% and 90.6% for CO2 laser and the open techniques respectively.</p><p><b>CONCLUSIONS</b>Compared to the open technique, transoral CO2 laser epiglottectomy is a well-tolerated and promising resection technique with low morbidity for early epiglottic carcinomas, and the identification of landmarks is useful for entire resection of epiglottis.</p>