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Based on the duality of "healthy" and "pathogenic" of the immune system in physiological and pathological states, and combined with the analogy between "immune function" and "healthy qi", the theory of "transformation of healthy qi into pathogenic qi" was proposed to guide the pattern identification and treatment of autoimmune diseases. The theory of "transformation of healthy qi into pathogenic qi" means that "healthy qi", which is originally used by the body's original ability to defend and remove harmful factors or normal functional activities, transformed into "pathogenic qi", which is factors that damage and destroy the human body or abnormal body state. In the pathogenesis of autoimmune diseases, the pathogenic factors and causes of congenital endowment, tissue damage under the influence of external pathogens, abnormal function of zang-fu (脏腑) organs and meridians, abnormal transmission and transformation of qi, blood, body fluids was proposed. Autoimmune diseases have the dynamic mechanism of latent pathogen at early stage, internal and external contraction at the onset stage, and the expansion of the pathogenic qi at the complete period, and also have the characteristics of the specificity, invisibility and contradiction of healthy qi and pathogenic qi. In terms of treatment, it advocates the ideas of treatment with both attack and supplementation throughout the disease, identifying diseases with special prescriptions and formulas for specific diseases, dynamically adjusting treatment by identifying the remission and onsets of the disease, observing the changes in the dynamics of healthy qi transforming into pathogenic qi, and treating disease before it arises with early intervention.
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Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.
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PURPOSE: It is well documented that natural killer (NK) cytotoxicity against hepatocellular carcinoma (HCC) cells is impaired in HCC, which might account for the failure of anti-tumor immune response. miRNAs are considered as important regulators for the development and functions of NK cells. However, the entire role of miR-506 in NK cells remains far from being addressed. MATERIALS AND METHODS: The expressions of miR-506 and signal transducer and activator of transcription 3 (STAT3) mRNA in primary NK cells from HCC patients and healthy controls were detected by quantitative real-time PCR. NK cell cytotoxicity was assessed by CFSE/7AAD cytotoxicity assay and lactate dehydrogenase assay. Luciferase reporter assay, RNA immunoprecipitation assay, and western blot were conducted to confirm the interaction between miR-506 and STAT3. RESULTS: miR-506 expression was downregulated and STAT3 mRNA was upregulated in primary NK cells from HCC patients. Primary NK cells from HCC patients showed remarkably reduced cytotoxicity against SMMC7721 or HepG2 cells. NK cell cytotoxicity was positively correlated with miR-506 expression and negatively correlated with STAT3 mRNA expression. Additionally, miR-506 overexpression enhanced NK cell cytotoxicity against HCC cells, while miR-506 inhibitor showed the reverse effect. Moreover, miR-506 could suppress STAT3 expression by directly targeting 3′-untranslated regions of STAT3. A negative correlation between miR-506 and STAT3 mRNA expression in HCC patients was observed. Mechanistically, overexpressing STAT3 greatly reversed miR-506-mediated promotion of NK cell cytotoxicity against HCC cells. CONCLUSION: miR-506 enhanced NK cell cytotoxicity against HCC cells by targeting STAT3, suggesting that modulating miR-506 expression maybe a promising approach for enhancing NK cell-based antitumor therapies.
Assuntos
Humanos , Western Blotting , Carcinoma Hepatocelular , Células Hep G2 , Imunoprecipitação , Células Matadoras Naturais , L-Lactato Desidrogenase , Luciferases , MicroRNAs , Reação em Cadeia da Polimerase em Tempo Real , RNA , RNA Mensageiro , Fator de Transcrição STAT3RESUMO
Objective To observe the expression of Frizzled protein in mouse tooth germ at bell stage and explore the possible function of Wnt/Frizzled signal molecules. Methods Mouse embryos at 17 and 19 days of gestation (E17 and E19) as well as mice postnatal day 2 (PN2) were employed in our study. The frozen sections of the first lower molar were made and indirect immunofluorescence technique was carried out on the sections. The location of Frizzled protein was observed under the fluorescence microscope. Results Frizzled protein was expressed weakly in the inner- and outer- dental epithelium at E17. At E19,the positive staining was found to distribute at the summit of both pre-ameloblasts and pre-odontoblasts. At P2,Frizzled protein was expressed strongly at the summit of ameloblasts and odontoblasts. Conclusion Wnt/Frizzled signal molecules may be involved in the differentiation of ameloblasts and odontoblasts.