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PURPOSE: This study aimed to investigate the efficacy and safety of autologous platelet-rich plasma (PRP) and bone marrow mononuclear cells (BMMCs) grafting combined with core decompression (CD) in the treatment of Association Research Circulation Osseous (ARCO) II-IIIA stage non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: The clinical data of 44 patients (44 hips) with non-traumatic ONFH from December 2018 to December 2019 were retrospectively reviewed. Twenty-four patients underwent CD combined with autologous PRP and BMMCs grafting (PRP+BMMCs group), and 20 patients underwent core decompression alone (CD group). During a minimum follow-up of 36 months, radiographic outcomes were evaluated using X-ray, radiographic failure rates were compared, and Harris hip score (HHS) and visual analog scale (VAS) were selected to evaluate clinical outcomes. The percentage of patients with minimal clinically important difference (MCID) in both groups was analyzed. Clinical failure was defined as further total hip arthroplasty (THA) with Kaplan-Meier survival analysis. Surgical complications were recorded. RESULTS: All patients had well healed wounds, and no complications such as infection and thrombosis occurred. HHS and VAS scores in both the PRP+BMMCs and CD groups were better than those preoperatively (P<0.05). At the last follow-up, the HHS and VAS scores of the PRP+BMMCs group were significantly better than those of the CD group (P<0.05). In ARCO II-IIIA stage, 66.7% of the PRP+BMMCs group and 30.0% of the CD group achieved the MCID (P<0.05). The clinical and imaging failure rates in the PRP+BMMCs group were 12.5% and 20.8%, respectively, compared with 40.0% and 50.0% in the CD group (P<0.05). In ARCO II stage, the MCID, clinical and imaging failure rates of PRP+BMMCs group and CD group were 66.7% and 33.3% (P<0.05), 4.8% and 33.3% (P<0.05), 14.3% and 44.4% (P<0.05), respectively. The PRP+BMMCs group had better hip survival rate compared with CD group (P<0.05). CONCLUSION: CD combined with autologous PRP and BMMCs grafting is a safe and effective method for the treatment of ARCO II-IIIA stage non-traumatic ONFH, especially for ARCO II stage, effectively reducing the collapse rate of the femoral head and delaying or even avoiding THA.
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Necrose da Cabeça do Fêmur , Plasma Rico em Plaquetas , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Cabeça do Fêmur/cirurgia , Medula Óssea/cirurgia , Necrose da Cabeça do Fêmur/cirurgia , Descompressão Cirúrgica/métodos , Transplante ÓsseoRESUMO
PURPOSE: To investigate the clinical efficacy and safety of two different bone graft materials in the minimally invasive treatment of early and middle stage femoral head necrosis. METHODS: A total of 36 patients (39 hips) with avascular necrosis of the femoral head were divided into autologous iliac bone group (ABG) and bioceramics bone group (BBG). Both groups were treated with minimally invasive thick channel decompression to remove dead bone of femoral head. The ABG was treated with autologous iliac bone graft, and BBG was treated with ß-tricalcium phosphate bone graft. The operation time, intra-operative blood loss, haemoglobin, and haematocrit were recorded at three and seven days post-operatively. The clinical efficacy and safety were evaluated by Harris score and imaging examination before, and after treatment and at follow-up stages. RESULTS: The patients were followed up for 24 to 45 (average 29.27 ± 3.56) months. The BBG was significantly better than the ABG in terms of operation time, intra-operative blood loss, haemoglobin, and haematocrit value at three days. Compared with pre-operative, the Harris score of the two groups at 12 months after operation was significantly improved. The Harris score and the imaging evaluation of the last follow-up exhibited significantly better outcome in BBG than those of ABG. CONCLUSION: Bioceramics and autologous iliac bone minimally invasive treatment of early and medium-term femoral head necrosis exhibited satisfactory clinical efficacy in the short and medium-term. The bioceramics graft materials have the advantages of reducing trauma, bleeding, operation time, and quick recovery of post-operative functions.
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Necrose da Cabeça do Fêmur , Cabeça do Fêmur , Transplante Ósseo , Descompressão Cirúrgica , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/cirurgia , Seguimentos , Humanos , Ílio , Resultado do TratamentoRESUMO
In this study, we aim to compare and analyze the biomechanical repair and clinical efficacy of osteonecrosis of the femoral head (ONFH) with the use of metal trabecular bone reconstruction system and free vascularized fibular graft. The study enrolled 66 adult patients from medical records of nontraumatic ARCO 2A-3B stage ONFH. A simple ONFH model without surgical treatment was established in 13 cases, 29 cases were treated with metal trabecular bone reconstruction system, and 24 cases were treated with free vascularized fibular graft. Computer-recognized and extracted femur outlines were imported, and three-dimensional reconstructions were performed. The stress concentration and stress peak value were analyzed, and the Harris score, visual analog scale pain score, and operation status of the above patients were compared. Finally, quality of life assessment was performed using SF-36 scale. Metal trabecular bone reconstruction system provided less operation time, blood loss, and the total length of postoperative hospital stay than free vascularized fibular graft. Metal trabecular bone reconstruction system promoted bone reconstruction, increased bone mineral density and Harris score. The total clinical effective rate of young patients (20-40 years) was higher than that of older patients (41-60 years). Metal trabecular bone reconstruction system provided higher physical component summary, mental component summary, and role/social component summary than free vascularized fibular graft. This study demonstrates that both metal trabecular bone reconstruction system and free vascularized fibular graft can prevent or delay the progression of ONFH, while metal trabecular bone reconstruction system is a better choice because of better short-term clinical efficacy.
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Transplante Ósseo , Osso Esponjoso/patologia , Osso Esponjoso/cirurgia , Necrose da Cabeça do Fêmur/cirurgia , Fíbula/irrigação sanguínea , Metais/farmacologia , Neovascularização Fisiológica , Cicatrização , Adulto , Fenômenos Biomecânicos , Osso Esponjoso/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/fisiopatologia , Fíbula/cirurgia , Análise de Elementos Finitos , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Procedimentos de Cirurgia Plástica , Estresse Mecânico , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To describe the rationale, the surgical technique, and the short-term follow-up results of a new minimally invasive treatment of osteonecrosis of the femoral head (ONFH) with an angioconductive bioceramic rod (ABR) implant. METHODS: Sixty-two patients (72 hips) with ARCO stage IIA-IIIC ONFH treated with the minimally invasive ABR from January 2012 to December 2016 were reviewed (17 females, 45 males, mean age 44.49). This technique used the angioconductive properties of the porous implant to repair the necrosis by driving vascularization from the trochanter to the necrotic area. Patients had a mean follow-up period of 26.74 months. The outcomes were evaluated by hip joint survival, radiograph, and the Harris Hip Score (HHS). The complications occurred during the treatment period were recorded. RESULTS: No serious post-operative complications occurred during the treatment. The overall joint survival rate was 90.27%, with seven conversions to THA. Improvements were observed in 23 (31.95%) hips, 24 (33.33%) hips remained stable, and 25 (34.72%) hips had worse results according to the radiographic evaluation. The mean HHS at the end follow-up significantly improved compared to the pre-operative mean HHS (82.27 vs 58.14, p < 0.001). In both radiographic evaluation and HHS, the treatment was more effective on patients beneath 44 years old (p < 0.05); ARCO stage II compared to stage III (p < 0.05); and China-Japan Friendship Hospital (CJFH) type C compared to CJFH type L (p < 0.05). CONCLUSIONS: The minimally invasive treatment of ONFH with ABR showed promising results in delaying or even terminating the progression of the necrosis and improving hip function, especially in younger patients and in the early stages of the disease.
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Substitutos Ósseos/administração & dosagem , Transplante Ósseo/métodos , Necrose da Cabeça do Fêmur/cirurgia , Articulação do Quadril/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adolescente , Adulto , Idoso , Substitutos Ósseos/efeitos adversos , Feminino , Seguimentos , Articulação do Quadril/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: This study summarises the clinical efficacy of sartorius muscle-pedicle bone graft in osteonecrosis of the femoral head. METHODS: A total of 58 patients, including 53 men (61 hips) and five women (6 hips) with osteonecrosis of the femoral head, underwent sartorius muscle-pedicle bone grafting. Association Research Circulation Osseous (ARCO) staging was performed. RESULTS: The ARCO staging revealed 23 hips of stage I, 36 hips of stage II and eight hips of stage III. The average surgical duration was 65 minutes (range 45-90 minutes). A total of 55 (64 hips) of the 58 patients undergoing surgery were followed up, with a mean follow-up duration of 34.48 months (range, 24-48 months) and a median of 34 months. The outcome was excellent in 27, good in 24, normal in two, and poor in 11 hips, with a total good rating of 79.68 %. The Harris score of the hip joints in the last follow-up was significantly improved compared with pre-surgical scores (P < 0.01). Imaging results showed that 21 hips were improved, 31 hips were stabilized and 12 hips were aggravated (of which 9 hips underwent total hip replacement). The survival rate of femoral head was 81.25 %. CONCLUSION: Sartorius muscle-pedicle bone graft significantly promotes repair of osteonecrosis of the femoral head, improves the Harris score of the hip joints, with good clinical efficacy. It effectively improves the survival rate of femoral head, delaying or preventing artificial hip replacement.
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Artroplastia de Quadril/efeitos adversos , Transplante Ósseo/métodos , Necrose da Cabeça do Fêmur/cirurgia , Cabeça do Fêmur/cirurgia , Articulação do Quadril/cirurgia , Músculo Esquelético/transplante , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To observe the curative effect of porous tantalum rod and Gugutou Huaisiyu Capsule (GHC) for steroid-induced osteonecrosis of femoral head (SONFH). METHODS: A total 60 hips of 50 SONFH patients were randomly assigned to the treatment group and the control group according to grouping time, 25 in each group (30 hips). Patients in the control group were implanted with porous tantalum rod, while those in the treatment group additionally took GHC (5 pills each time, three time per day for 2 successive months; and then twice per day for 4 successive months). Then all patients were followed-up to observe Harris hip score. The curative effect and the femoral head survival time were assessed. RESULTS: A total of 49 patients (59 hips) were followed-up. The Harris hip score of the two groups at the final follow-up was significantly improved after treatment, with statistical difference when compared with before treatment (P < 0.01). Besides, it was higher in the treatment group than in the control group. The curative effect and the survival time were superior in the treatment group, with statistical difference when compared with the control group (P < 0.05). CONCLUSIONS: Porous tantalum rod combined GHC got better effect in treating SONFH. It could significantly improve the function of affected hips and prolong the survival time of femoral head.
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Medicamentos de Ervas Chinesas/uso terapêutico , Necrose da Cabeça do Fêmur/tratamento farmacológico , Tantálio , Cápsulas , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Próteses e Implantes , Esteroides/efeitos adversosRESUMO
miR-27 plays a negative role in the regulation of adipogenesis. However, the molecular mechanism still remains to be clarified. In the present study, we found that miR-27 inhibits adipogenesis partially by repressing the early adipogenic transcription factor cAMP response element-binding protein by directly targeting its 3' untranslated region. In addition, we demonstrated that tumor necrosis factor-α (TNF-α) treatment up-regulates miR-27 through the NF-κB pathway. Furthermore, anti-miR-27 reduces the TNF-α-induced inhibition of adipogenesis. Simultaneously, the levels of miR-27 expression were decreased in mature adipocytes of obese mice when compared with lean mice. Our data revealed a novel mechanism of miR-27 in the regulation of adipogenesis.
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Adipócitos/citologia , Diferenciação Celular/fisiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , MicroRNAs/fisiologia , Regiões 3' não Traduzidas , Células 3T3-L1 , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação para Baixo , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Obesidade/genética , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
BACKGROUND: Osteonecrosis of the femoral head (ONFH) often leads to the collapse of the femoral head, ultimately resulting in patients undergoing premature total hip arthroplasty (THA). The surgical hip dislocation (SHD) technique is a type of hip-preserving surgery aimed at delaying or avoiding THA. This study aims to evaluate the clinical efficacy of SHD techniques through femoral head fovea fenestration and impaction bone grafting for the treatment of non-traumatic ONFH. METHODS: A retrospective analysis was conducted on the clinical data of 39 patients (39 hips) with non-traumatic ONFH who underwent SHD for treatment from 2016 to 2017. The Harris hip score (HHS) and the minimum clinically important difference (MCID) are used to evaluate clinical outcomes, while radiographic evaluations are conducted using X-rays. Kaplan-Meier survival analysis defined clinical failure as further THA, and conducted univariate survival analysis and Cox regression analysis. Any complications were recorded. RESULTS: All patients were followed up for 24-72 months, with an average of (60 ± 13.0) months. At the last follow-up, based on the HHS, 25 patients (64.1%) reported excellent and good clinical outcomes. 29 patients (74.3%) achieved MCID. Imaging evaluation of the postoperative femoral head status showed that 6 cases improved, 20 cases remained stable, and 13 cases showed progressed. Out of 39 hips, 12 hips had postoperative clinical failure, resulting in a clinical success rate of 69.2%. Association Research Circulation Osseous (ARCO) stage, China-Japan Friendship Hospital (CJFH) classification, and postoperative crutch-bearing time are risk factors for clinical failure. Postoperative crutch-bearing time of less than 3 months is an independent risk factor for clinical failure. After surgery, there was one case of sciatic nerve injury and one case of heterotopic ossification. There were no infections or non-union of the greater trochanter osteotomy. CONCLUSION: The SHD technique through the femoral head fovea fenestration and impaction bone grafting provides a safe and effective method for treating non-traumatic ONFH, with good mid-term clinical outcomes. ARCO staging, CJFH classification, and postoperative crutch-bearing time are risk factors that affect clinical outcomes after surgery and lead to further THA. Insufficient postoperative crutch-bearing time is an independent risk factor for clinical failure.
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Transplante Ósseo , Necrose da Cabeça do Fêmur , Humanos , Estudos Retrospectivos , Masculino , Feminino , Transplante Ósseo/métodos , Adulto , Necrose da Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/etiologia , Pessoa de Meia-Idade , Resultado do Tratamento , Luxação do Quadril/cirurgia , Luxação do Quadril/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Cabeça do Fêmur/diagnóstico por imagem , Seguimentos , Adulto JovemRESUMO
Coptisine (COP) has been shown to exhibit a wide range of anticancer properties, including in hepatocellular carcinoma (HCC). Nevertheless, the precise mechanism of COP in the treatment of HCC remains elusive. This study aims to investigate the potential mechanism of action of COP against HCC. By evaluating the anti-HCC activity of COP in different HCC cells lines and in xenografted nude mice, it was found that COP inhibited HCC in vitro and in vivo. Through RNA-Seq analysis, E2F7 was identified as a potential target of COP against HCC, as well as the cell cycle as a possible pathway. The overexpression of E2F7 and the inhibition of CHK1 demonstrated that COP inhibits the activity of HCC and induces G2/M phase arrest of HCC cells by down-regulating E2F7 and influencing the CHK1/CDC25A pathway. Finally, the promoter fragmentation experiments and chromatin immunoprecipitation revealed that COP down-regulated E2F7 by inhibiting the E2F4/NFYA/NFYB transcription factors. In conclusion, our study demonstrated that COP downregulates E2F7 by affecting key transcription factors, thereby inducing cell cycle arrest and inhibits HCC cell growth. This provides further evidence of the efficacy of COP in the treatment of tumors.
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Berberina , Carcinoma Hepatocelular , Regulação para Baixo , Fator de Transcrição E2F4 , Fator de Transcrição E2F7 , Pontos de Checagem da Fase G2 do Ciclo Celular , Neoplasias Hepáticas , Camundongos Nus , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Berberina/farmacologia , Berberina/análogos & derivados , Animais , Regulação para Baixo/efeitos dos fármacos , Camundongos , Fator de Transcrição E2F4/metabolismo , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Fator de Transcrição E2F7/metabolismo , Fator de Transcrição E2F7/genética , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Proliferação de Células/efeitos dos fármacos , Quinase 1 do Ponto de Checagem/metabolismo , Quinase 1 do Ponto de Checagem/antagonistas & inibidoresRESUMO
Chronic atrophic gastritis (CAG) is a complex disease characterized by atrophy and inflammation in gastric mucosal tissue, especially with high expression of interleukins. However, the interaction and mechanisms between interleukins and gastric mucosal epithelial cells in CAG remain largely elusive. Here, we elucidate that IL-33 stands out as the predominant inflammatory factor in CAG, and its expression is induced by H. pylori and MNNG through the ROS-STAT3 signaling pathway. Furthermore, our findings reveal that the IL-33/ST2 axis is intricately involved in the progression of CAG. Utilizing phosphoproteomics mass spectrometry, we demonstrate that IL-33 enhances autophagy in gastric epithelial cells through the phosphorylation of AMPK-ULK1 axis. Notably, inhibiting autophagy alleviates CAG severity, while augmentation of autophagy exacerbates the disease. Additionally, ROS scavenging emerges as a promising strategy to ameliorate CAG by reducing IL-33 expression and inhibiting autophagy. Intriguingly, IL-33 stimulation promotes GKN1 degradation through the autolysosomal pathway. Clinically, the combined measurement of IL-33 and GKN1 in serum shows potential as diagnostic markers. Our findings unveil an IL-33-AMPK-ULK1 regulatory mechanism governing GKN1 protein stability in CAG, presenting potential therapeutic targets for its treatment.
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Gastrite Atrófica , Helicobacter pylori , Hormônios Peptídicos , Humanos , Proteínas Quinases Ativadas por AMP , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Mucosa Gástrica , Interleucina-33 , Peptídeos e Proteínas de Sinalização Intracelular , Espécies Reativas de OxigênioRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Characterized by inflammation of the gastric mucosa, atrophy of gastric gland cells, and intestinal metaplasia, Chronic Atrophic Gastritis (CAG) is a precancerous lesion disease. In traditional Chinese medicine, Rhizoma Coptidis (RC) is extensively used for treating gastrointestinal disorders, mainly because RC alkaloids-based extracts are the main active pharmaceutical ingredients. Total Rhizoma Coptidis extracts (TRCE) is a mixture of Rhizoma Coptidis extracts from Rhizoma Coptidis with alkaloids as the main components. However, the efficacy and mechanism of TRCE on CAG need further study. AIM OF THE STUDY: To explore the therapeutic effect and underlying mechanisms of action of TRCE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) using network pharmacological analysis. MATERIALS AND METHODS: The amelioration effect of TRCE on CAG was evaluated in MNNG-induced CAG mice. The pathological severity of the mice was evaluated through H&E staining. Detection of gastric mucosal parietal cell loss was conducted using immunofluorescence staining, and serum indices were measured using ELISA. Additionally, the active compounds and drug targets of Rhizoma Coptidis were curated from the STP, SEA, and TCMSP databases, alongside disease targets of CAG sourced from PharmGkb, OMIM, and GeneCards databases. By mapping drug targets to disease targets, overlapping targets were identified. A shared protein-protein interaction (PPI) and drug target network were constructed for the overlapping targets and analyzed for KEGG enrichment. RESULTS: The results of animal experiments demonstrate that TRCE has the potential to improve the CAG process in mice. In conjunction with disease characteristics, cyberpharmacology analysis has identified nine core compounds, 151 targets, 10 core targets, and five significant inflammatory pathways within the compound-target-pathway network. Furthermore, there is a remarkable coincidence rate of 98% between the core compound targets of TRCE and the targets present in the CAG disease database. The accurate search and calculation of literature reports indicate that the coverage rate for 121 predicted core targets related to CAG reaches 81%. The primary characteristic of CAG lies in its inflammatory process. Both predicted and experimental findings confirm that TRCE can regulate ten key inflammation-associated targets (TP53, STAT3, AKT1, HSP90AA1, TNF, IL-6, MAPK3, SRC, JUN, and HSP90AA1) as well as inflammation-related pathways (MAPK, HIF-1, Toll-Like Receptor, IL-17, TNF, and other signaling pathways). These mechanisms mitigate inflammation and reduce gastric mucosal damage in CAG mice. CONCLUSIONS: In conclusion, TRCE was shown to alleviate CAG by modulating TP53, STAT3, AKT1, HSP90AA1, TNF, IL-6, MAPK3, SRC, JUN, and EGFR, as demonstrated by combined network pharmacology and biological experiments. In conclusion, our study provides a robust foundation for future clinical trials evaluating the efficacy of RC in treating CAG.
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ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic steatohepatitis (NASH) has emerged as a major cause of cirrhosis and hepatocellular carcinoma, posing a significant threat to public health. Rhizoma Coptidis, a traditional Chinese medicinal herb has been shown to have significant curative effects on liver diseases. Total Rhizoma Coptidis Alkaloids (TRCA) is a primarily alkaloid mixture extracted from Rhizoma Coptidis, and its constituents are widely accepted to have hepatoprotective effects. AIM OF THE STUDY: This work aimed to investigate the efficacy and potential mechanisms of TRCA in ameliorating NASH through both in vitro experiments and in vivo mouse models. MATERIALS AND METHODS: The study employed a mice model induced by a high-fat diet (HFD) to evaluate the effectiveness and pharmacological mechanisms of TRCA in alleviating NASH. Transcriptomic sequencing and network pharmacology were used to explore the possible targets and mechanisms of TRCA to ameliorate NASH. Further validation was performed in free fatty acid (FFA)-induced human hepatocytes (LO2) and human hepatocellular carcinoma cells (HepG2). RESULTS: TRCA effectively ameliorated the main features of NASH such as lipid accumulation, hepatitis and hepatic fibrosis in the liver tissue of mice induced by HFD, as well as improved glucose tolerance and insulin resistance in mice. Combined with transcriptomic and network pharmacological analyses, 68 core targets associated with the improvement of NASH by TRCA were obtained. According to the KEGG results, the core targets were significantly enriched in the PI3K-AKT signaling pathway whereas TRCA ameliorated the aberrant down-regulation of the PI3K-AKT signaling pathway induced by HFD. Furthermore, the five highest-ranked genes were obtained by PPI network analysis. Moreover, our findings suggest that TRCA may impede the progression of HFD-induced NASH by regulating the expression of PPARG, MMP9, ALB, CCL2, and EGFR. CONCLUSIONS: TRCA can ameliorate HFD-induced liver injury by modulating aberrant downregulation of the PI3K-AKT signaling pathway. Key proteins such as PPARG, MMP9, ALB, CCL2, and EGFR may be critical targets for TRCA to ameliorate NASH. This finding supports using Rhizoma Coptidis, a well-known herbal medicine, as a potential therapeutic agent for NASH.
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Alcaloides , Antineoplásicos , Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metaloproteinase 9 da Matriz , Carcinoma Hepatocelular/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases , Farmacologia em Rede , PPAR gama , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Perfilação da Expressão Gênica , Receptores ErbBRESUMO
Disulfidptosis is a newly discovered cell death pattern that has been less studied in head and neck squamous carcinoma (HNSCC). Exploring the molecular features of different subtypes of HNSCC based on disulfidptosis-associated genes (DAGs) is important for HNSCC. In addition, immunotherapy plays a pivotal role in the treatment of HNSCC. Exploring the sensitivity of immunotherapies and developing predictive models is essential for HNSCC. We analyzed the expression and mutational status of DAGs in 790 HNSCC patients and correlated the dates with clinical prognosis. HNSCC patients were divided into 2 groups based on their DAG expression. The relationship between DAGs, risk genes, and the immune microenvironment was analyzed using the CIBERSORT algorithm. A disulfidptosis risk model was constructed based on 5 risk genes using the LASSO COX method. To facilitate the clinical applicability of the proposed risk model, we constructed column line plots and performed stem cell correlation analysis and antitumor drug sensitivity analysis. Two different disulfidptosis-associated clusters were identified using consistent unsupervised clustering analysis. Correlations between multilayer DAG alterations and clinical characteristics and prognosis were observed. Then, a well-performing disulfidptosis-associated risk model (DAG score) was developed to predict the prognosis of HNSCC patients. We divided patients into high-risk and low-risk groups based on the DAG score and found that patients in the low-risk group were more likely to survive than those in the high-risk group (Pâ <â .05). A high DAG score implies higher immune cell infiltration and increased mutational burden. Also, univariate and multivariate Cox regression analyses revealed that the DAG score was an independent prognostic predictor for patients with HNSCC. Subsequently, a highly accurate predictive model was developed to facilitate the clinical application of DAG scores, showing good predictive and calibration power. Overall, we present a comprehensive overview of the DAG profile in HNSCC and develop a new risk model for the therapeutic status and prognosis of patients with HNSCC. Our findings highlight the potential clinical significance of DAG and suggest that disulfidptosis may be a potential therapeutic target for patients with HNSCC.
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Neoplasias de Cabeça e Pescoço , Imunoterapia , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Algoritmos , Neoplasias de Cabeça e Pescoço/genética , Microambiente TumoralRESUMO
A variety of techniques have been used for treating avascular necrosis of the femoral head (ANFH), but have frequently failed. In this study, we proposed a ß-TCP system for the treatment of ANFH by boosting revascularization and bone regeneration. The angio-conductive properties and concurrent osteogenesis of the highly interconnected porous ß-TCP scaffold were revealed and quantified through an in vivo model that simulated the ischemic environment of ANFH. Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation, and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone, along with continuous material degradation and bone regeneration. For translational application, we further conducted a multi-center open-label clinical trial to assess the efficacy of the ß-TCP system in treating ANFH. Two hundred fourteen patients with 246 hips were enrolled for evaluation, and 82.1% of the operated hips survived at a 42.79-month median follow-up. The imaging results, hip function, and pain scores were dramatically improved compared to preoperative levels. ARCO stage â ¡ disease outperformed stage â ¢ in terms of clinical effectiveness. Thus, bio-adaptive reconstruction using the ß-TCP system is a promising hip-preserving strategy for the treatment of ANFH.
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To explore and evaluate the imaging manifestations of postoperative complications of bone and joint infections based on deep learning, a retrospective study was performed on 40 patients with bone and joint infections in the Department of Orthopedics of Orthopedics Hospital of Henan Province of Luoyang City. Sensitivity and Dice similarity coefficient (DSC) were used to evaluate the image results by convolutional neural network (CNN) algorithm. Imaging features of postoperative complications in 40 patients were analyzed. Then, three imaging methods were used to diagnose the features. Sensitivity and specificity were used to evaluate the diagnostic performance of three imaging methods for imaging features. Compared with professional doctors and biomarker algorithms, the sensitivity of CNN algorithm proposed was 90.6%, and DSC was 84.1%. Compared with traditional methods, the CNN algorithm has higher image resolution and wider and more accurate lesion area recognition and division. The three manifestations of soft tissue abscess, periosteum swelling, and bone damage were postoperative imaging features of bone and joint infections. In addition, compared with X-ray, CT examination and MRI examination were better for the examination of imaging characteristics. CT and MRI had higher sensitivity and specificity than X-ray. The experimental results show that CNN algorithm can effectively identify and divide pathological images and assist doctors to diagnose the images more efficiently in clinic.
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Aprendizado Profundo , Humanos , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos RetrospectivosRESUMO
BACKGROUND: This study aimed to evaluate the clinical efficacy of femoral head and neck fenestration combined with autologous bone mixed with ß-tricalcium phosphate porous bioceramic bone (light bulb procedure) through Orthopdische Chirurgie München approach (OCM approach) for pre-collapse non-traumatic osteonecrosis of the femoral head(ONFH). METHODS: The clinical data of 47 patients (47 hips) with ONFH were retrospectively reviewed. The Harris hip score (HHS) was used to evaluate the clinical outcomes. Imaging was assessed by X-ray. Clinical failure was defined as postoperative total hip arthroplasty (THA) or the HHS was poor (< 70). The Kaplan-Meier survival curve was used to conduct a univariate analysis of risk factors. The analysis factors included gender, age, International Association Research Circulation Osseous (ARCO) stage, etiology, body mass index (BMI), 25-hydroxyvitamin D (25(OH)D), and type I collagen carboxy-terminal peptide (CTX). The COX multivariate risk model was used to analyze the risk factors. RESULTS: All the 47 hips were followed up for 24-58 months, with an average of 45 months. The Harris score (76.29 ± 10.38) at the last follow-up was significantly higher than the preoperative HHS (64.45 ± 2.93) (P < 0.05). The postoperative HHS was excellent with a success rate of 36.17%. Postoperative imaging evaluation showed that 9 hips improved, 28 hips stabilized, and 10 hips progressed. Moreover, 17 out of 47 hips were defined as a postoperative clinical failure and the success rate was 63.83%. 25(OH)D and preoperative ARCO stage were risk factors for postoperative clinical failure (P < 0.05). The COX multivariate risk model analysis showed that IIIA stage was an independent risk factor for postoperative clinical failure (P < 0.05). CONCLUSIONS: The head and neck fenestration and bone grafting via the OCM approach in the treatment of non-traumatic ONFH in the pre-collapse stage can achieve good clinical outcomes. 25(OH)D deficient patients and ARCO IIIA patients had a higher failure rate of bone graft using this approach.
Assuntos
Necrose da Cabeça do Fêmur , Cabeça do Fêmur , Transplante Ósseo , Fosfatos de Cálcio , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/cirurgia , Seguimentos , Humanos , Porosidade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To observe the progress of disease activity and sacroiliac joint imaging in patients with ankylosing spondylitis treated by extracorporeal shockwave combined with conventional oral medicine, and find a new safe and effective therapeutic method. METHODS: The clinical data of 30 patients with ankylosing spondylitis treated from January 2018 to December 2018 were retrospectively analyzed. Including 20 males and 10 females, aged from 18 to 50 years with an average of (34.50±9.60) years. All 30 patients had different degrees of sacroiliac joint bone marrow edema on MRI before treatment. Thirty patients were divided into treatment group and control group according to different treatment methods. Among them, 15 cases in control group were treated with non-steroidal anti-inflammatory drugs and sulfasalazine enteric-coated tablets, for the 15 cases in treatment group, in addition to oral medicine in line with control group, electronic focusing high-energy extracorporeal shockwave therapy was added. The course of disease, age, pre- and post-treatment erythrocyte sedimentation rate, C-reactive protein in the two groups were analyzed; and visual analogue scale (VAS) and spondyloarthritis research consortium Canada (SPARCC) scoring system were used to evaluate the pain of the sacroiliac joint and the structural damage of the sacroiliac joint;Bath ankylosing spondylitis disease activity index (BASDAI) was calculated. RESULTS: All patients were followed up for at least 3 months. One month after treatment, VAS, and SPARCC scores in treatment group were significantly better than in control group (P<0.05). After 1 month of treatment, there was no significant difference in BASDAI, erythrocyte sedimentation rate and C-reactive protein between two groups(P>0.05). VAS, BASDAI, SPARCC, erythrocyte sedimentation rate, and C-reactive protein of all patients after treatment were significantly improved compared with those before treatment (P< 0.01). CONCLUSION: Electronic focusing high-energy extracorporeal shockwave combined with conventional oral medicine in the treatment of ankylosing spondylitis has a good clinical effect in rapidly relieving pain, improving disease activity, and preventing imaging progress. In addition, it is safe and non-invasive, which is worthy of clinical application.
Assuntos
Ondas de Choque de Alta Energia , Espondilite Anquilosante , Eletrônica , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondilite Anquilosante/terapiaRESUMO
AWPPH is a newly discovered long noncoding (lnc)RNA that plays an oncogenic role in development of several types of malignancies, whiles its involvement in non-traumatic osteonecrosis of femoral head (ONFH) is unknown. Therefore, the present study aimed to investigate the functionality of AWPPH in non-traumatic ONFH. Blood and mesenchymal stem cells (MSCs) were obtained from both non-traumatic ONFH patients and healthy controls, and expression of AWPPH in those tissues was detected by RT-qPCR. Receiver operating characteristic curve analysis was performed to investigate the diagnostic value of lncRNA AWPPH expression for non-traumatic ONFH. Bone morphogenic protein (BMP-2) was used to treat MSCs to induce osteogenic differentiation and the effects on lncRNA AWPPH expression was detected by RT-qPCR. LncRNA AWPPH overexpression and short hairpin (sh)RNA silencing cell lines were established and the effects on runt-related transcription factor 2 (Runx2) expression were detected by western blotting. It was demonstrated that AWPPH was significantly downregulated in non-traumatic ONFH patients compared with in healthy controls in both MSCs and serum. Expression of AWPPH in MSCs and serum is a sensitive diagnostic marker for non-traumatic ONFH. Expression of AWPPH exhibited no significant correlation with patients' age, gender and living habits, but was significantly correlated with course of disease. BMP-2 treatment significantly increased the expression level of AWPPH in human MSCs from bone marrow (hMSC-BM). AWPPH overexpression promoted, while AWPPH short hairpin RNA silencing inhibited the expression of Runx2 expression in hMSC-BM cells. Therefore, it was concluded that lncRNA AWPPH may participate in the development of ONFH by upregulating Runx2.
RESUMO
The objective of this retrospective study was to evaluate the efficacy of high-energy focused extracorporeal shock wave therapy (HF-ESWT) on painful bone marrow edema syndrome (BMES) of the hip and shorten the natural course of disease.Thirty-four consecutive patients with BMES of the hip were treated with HF-ESWT in our department between August 2017and July 2018. The progression and treatment results of BMES were evaluated by imaging examination and clinical outcomes. The clinical outcomes include hip pain and function which were measured using the visual analog scale (VAS) and Harris hip score (HHS), respectively, and the VAS and HHS of all patients were calculated and evaluated before treatment (s0), at 1 month (s1), 3 months (s2), 6 months (s3)post-treatment. Imaging examination including Pelvic radiographs and frog views and double hip magnetic resonance imaging (MRI) were also obtained and scheduled before treatment, at 1, 3, 6, and the final follow-up post-treatment to exclude avascular necrosis and other pathology.All patients successfully completed the treatment and follow-up. Compared with pretherapy, the pain was alleviated to varying degrees and the HHS was significantly improved, and the VAS was significantly reduced at S1-2 (1- and 3-months post-treatment) after therapeutic intervention (Pâ<â.05). The mean improvements were strongly statistically significant between S0 and S1 and between S1 andS2 (Pâ<â.0001) and less significant between S2 and S3 (Pâ<â.01). The mean improvement between 6 months (S3) and final follow-up (more than 12 months) was not statistically significant. The MRI findings demonstrated that the diffuse BMES in the femoral head and neck disappeared completely.HF-ESWT is a safe, effective, reliable, and noninvasive treatment in patients with painful BMES of the hip, and it can accelerate the recovery of BMES of the hip, shorten the treatment time and course of disease, improve hip joint function and the quality of life of patients.