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BACKGROUND: Cryoablation (Cryo) is a minimally invasive treatment for tumors. Cryo can activate the body's immune response, although it is typically weak. The immune response induced by Cryo in hepatocellular carcinoma (HCC) is poorly understood. PD-1 and CTLA-4 monoclonal antibodies are immune checkpoint inhibitors used in immunotherapy for tumors. The combined use of these antibodies with Cryo may enhance the immune effect. METHODS: A Balb/c mouse model of HCC was established and treated with Cryo, immune checkpoint blockade (ICB), or Cryo + ICB (combination therapy). The growth trend of right untreated tumors and survival time of mice were determined. The expression of apoptosis-related proteins was detected by Western blot (WB) assay. The percentages of immune cells and immunosuppressive cells were analyzed by flow cytometry. The numbers of infiltrating T lymphocytes were checked by immunohistochemistry, and the levels of T-cell-associated cytokines were detected by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) assays and Enzyme-Linked Immunosorbent Assays (ELISA) assays. RESULTS: Cryo + ICB inhibited the growth of right untreated tumors, promoted tumor cell apoptosis, and prolonged the survival time of mice. Local T-cell infiltration in right tumor tissues increased after the combination therapy, while the number of immunosuppressive cells was significantly reduced. In addition, the combination therapy may induce the production of multiple Th1-type cytokines but reduce the production of Th2-type cytokines. CONCLUSIONS: Cryo can activate CD8+ and CD4+ T-cell immune responses. Cryo + ICB can relieve the immunosuppressive tumor microenvironment and shift the Th1/Th2 balance toward Th1 dominance, further enhancing the Cryo-induced T-cell immune response and resulting in a stronger antitumor immune response.
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Carcinoma Hepatocelular , Criocirurgia , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Camundongos Endogâmicos BALB C , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Camundongos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Criocirurgia/métodos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Modelos Animais de Doenças , Linhagem Celular TumoralRESUMO
Patients with hepatocellular carcinoma (HCC) display poor prognosis because HCC involves a high rate of metastasis and regrowth. Herein, we present an effective strategy to treat HCC using magnetic hyperthermia therapy (MHT)-enhanced cancer immunotherapy combined with transcatheter arterial embolization (TAE). Uniform liquid metal microspheres (LM MSs) obtained by microfluidic technology with powerful eddy-thermal effects could be used as both MHT and TAE agents for effective cancer therapy. The eddy-thermal effect of LM MSs demonstrated effective MHT, whereas LM MS-induced MHT boosted the immune system, promoted immune cell infiltration, and further stimulated powerful immune responses to suppress the growth of distant tumors, together with immune checkpoint blockade therapy. Furthermore, LM MS-lipiodol dispersion displayed excellent efficacy of the combined MHT-TAE in the orthotopic rabbit liver cancer model. Our work not only highlighted that LM MSs could act as effective MHT agents to achieve MHT-enhanced immunotherapy but also presented the significant promise of combining MHT with TAE for the efficient treatment of large orthotopic liver tumors.
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Carcinoma Hepatocelular , Embolização Terapêutica , Hipertermia Induzida , Neoplasias Hepáticas , Animais , Coelhos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Microesferas , Metais , Imunoterapia , Fenômenos MagnéticosRESUMO
Tumor-associated macrophages (TAMs)-based immunotherapy is a promising strategy. Since TAMs are mainly composed of M2-type macrophages, they have a promoting effect on tumor growth, invasion, and metastasis. M2-type macrophages contain a specific receptor CD163 on their surface, providing a prerequisite for active targeting to TAMs. In this study, we prepared CD163 monoclonal antibody modified doxorubicin-polymer prodrug nanoparticles (abbreviated as mAb-CD163-PDNPs) with pH responsiveness and targeted delivery. First, DOX was bonded with the aldehyde group of a copolymer by Schiff base reaction to form an amphiphilic polymer prodrug, which could self-assemble into nanoparticles in the aqueous solution. Then, mAb-CD163-PDNPs were generated through a "Click" reaction between the azide group on the surface of the prodrug nanoparticles and dibenzocyclocytyl-coupled CD163 monoclonal antibody (mAb-CD163-DBCO). The structure and assembly morphology of the prodrug and nanoparticles were characterized by 1H NMR, MALDI-TOF MS, FT-IR UV-vis spectroscopy, and dynamic light scattering (DLS). In vitro drug release behavior, cytotoxicity, and cell uptake were also investigated. The results show that the prodrug nanoparticles have regular morphology and stable structure, especially mAb-CD163-PDNPs, which can actively target TAMs at tumor sites, respond to the acidic environment in tumor cells, and release drugs. While depleting TAMs, mAb-CD163-PDNPs can actively enrich drugs at the tumor site and have a strong inhibitory effect on TAMs and tumor cells. The result of the in vivo test also shows a good therapeutic effect, with a tumor inhibition rate of 81%. This strategy of delivering anticancer drugs in TAMs provides a new way to develop targeted drugs for immunotherapy of malignant tumors.
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AIM: To test the contributions of self-efficacy, resilience, social support, and negative moods (i.e., anxiety, depression) to patient activation among persons with spinal cord injury (SCI). METHODS: One hundred and twenty-two participants with SCI were recruited from the spinal surgery department at a large general hospital. During the period before discharge after surgery, standardized self-assessment questionnaires were used to collect data on patient activation, self-efficacy, resilience, social support, anxiety, depression, demographics (age, gender, education, marital status), and disease-related information (etiologies, level of injury, American Spinal Injury Association Impairment Scale score). Hierarchical regression analysis, mediation analysis, and moderation analysis were performed in SPSS, Amos, and Jamovi to determine the influencing factors of patient activation. RESULTS: Self-efficacy, resilience, social support, anxiety, and depression uniquely explained 38.2% (p < .001) of the variance in patient activation after controlling for demographic and disease-related covariates. The full model explained 53.7% (p < .001) of the variance in patient activation. In the mediation analysis, self-efficacy, resilience, and social support had partial mediating effects (p < .05). In the moderation analysis, marital status moderated the relationship between self-efficacy and patient activation (p < .05). CONCLUSIONS: Activation of persons with SCI is a positive psychosocial resource related to higher self-efficacy, resilience, and social support. Marital status may affect activation in persons with SCI. The causal relationship between these psychosocial variables needs to be proved by further intervention studies.
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Autoeficácia , Traumatismos da Medula Espinal , Humanos , Estudos Transversais , Inquéritos e Questionários , Alta do Paciente , Traumatismos da Medula Espinal/psicologiaRESUMO
BACKGROUND: It has been demonstrated that cryoablation (Cryo) causes specific T-cell immune responses in the body; however, it is not sufficient to prevent tumor recurrence and metastasis. In this report, we evaluated changes in the tumor immune microenvironment (TIME) in distant tumor tissues after Cryo and investigated the immunosuppressive mechanisms that limit the efficacy of Cryo. METHODS: Bilateral mammary tumor models were established in mice, and we first observed the dynamic changes in immune cells and cytokines at different time points after Cryo. Then, we confirmed that the upregulation of PD-1 and PD-L1 signaling in the contralateral tumor tissue was closely related to the immunosuppressive state in the TIME at the later stage after Cryo. Finally, we also evaluated the synergistic antitumor effects of Cryo combined with PD-1 monoclonal antibody (mAb) in the treatment of breast cancer (BC) mouse. RESULTS: We found that Cryo can stimulate the body's immune response, but it also induces immunosuppression. The elevated PD-1/PD-L1 expression in distant tumor tissues at the later stage after Cryo was closely related to the immunosuppressive state in the TIME but also created the conditions for Cryo combined with PD-1 mAb for BC mouse treatment. Cryo + PD-1 mAb could improve the immunosuppressive state of tumors and enhance the Cryo-induced immune response, thus exerting a synergistic antitumor effect. CONCLUSIONS: The PD-1/PD-L1 axis plays an important role in suppressing Cryo-induced antitumor immune responses. This study provides a theoretical basis for Cryo combined with PD-1 mAb therapy in clinical BC patients.
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Anticorpos Monoclonais , Criocirurgia , Neoplasias Mamárias Experimentais , Animais , Camundongos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/farmacologia , Antígeno B7-H1/farmacologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral , Neoplasias Mamárias Animais , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/cirurgiaRESUMO
OBJECTIVE: The aim of this study was to build a convolutional neural network (CNN)-based prediction model of glioblastoma (GBM) molecular subtype diagnosis and prognosis with multimodal features. METHODS: In total, 222 GBM patients were included in the training set from Sun Yat-sen University Cancer Center (SYSUCC) and 107 GBM patients were included in the validation set from SYSUCC, Xuanwu Hospital Capital Medical University, and the First Hospital of Jilin University. The multimodal model was trained with MR images (pre- and postcontrast T1-weighted images and T2-weighted images), corresponding MRI impression, and clinical patient information. First, the original images were segmented using the Multimodal Brain Tumor Image Segmentation Benchmark toolkit. Convolutional features were extracted using 3D residual deep neural network (ResNet50) and convolutional 3D (C3D). Radiomic features were extracted using pyradiomics. Report texts were converted to word embedding using word2vec. These three types of features were then integrated to train neural networks. Accuracy, precision, recall, and F1-score were used to evaluate the model performance. RESULTS: The C3D-based model yielded the highest accuracy of 91.11% in the prediction of IDH1 mutation status. Importantly, the addition of semantics improved precision by 11.21% and recall in MGMT promoter methylation status prediction by 14.28%. The areas under the receiver operating characteristic curves of the C3D-based model in the IDH1, ATRX, MGMT, and 1-year prognosis groups were 0.976, 0.953, 0.955, and 0.976, respectively. In external validation, the C3D-based model showed significant improvement in accuracy in the IDH1, ATRX, MGMT, and 1-year prognosis groups, which were 88.30%, 76.67%, 85.71%, and 85.71%, respectively (compared with 3D ResNet50: 83.51%, 66.67%, 82.14%, and 70.79%, respectively). CONCLUSIONS: The authors propose a novel multimodal model integrating C3D, radiomics, and semantics, which had a great performance in predicting IDH1, ATRX, and MGMT molecular subtypes and the 1-year prognosis of GBM.
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Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine treatment combining surgical debridement with anti-infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a long-term antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum-based nanodots (MoO3-X ) for healing the DUs are reported. The ROS scavenging ability of MoO3-X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO3-X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin-resistant Staphylococcus aureus, manifesting the potent application prospect of MoO3-X nanodots for diabetic wound therapy.
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Diabetes Mellitus , Staphylococcus aureus Resistente à Meticilina , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Espécies Reativas de Oxigênio , Úlcera , CicatrizaçãoRESUMO
Glioblastoma (GBM) immunotherapy, which blocks the checkpoint inhibitor molecule T cell immunoglobulin domain and mucin domain-3 (Tim-3), has potential therapeutic applications. However, not all patients do benefit from the targeted therapy. This study aimed to explore Tim-3 expression correlated chemokine profiles and immune cell infiltration and investigate their potential as prognostic markers of glioblastoma (GBM) immunotherapy. We analyzed transcriptional data of GBM from TCGA database, to measure Tim-3 expression by R package DESeq2 analysis and observed differentially expressed genes in GBM samples with high Tim-3 expression levels. We also probed the relative gene enrichment pathways. Tim-3 expression was evident in biological processes including the recruitment of immune cells. We also identified some chemokines related to Tim-3 expression. The expression levels of CCL18, CXCL13 and CCL7 were significantly higher in GBM tissues with high Tim-3 expression than in GBM tissues with low Tim-3 expression. In addition, exploring the relationship between immune cell infiltration and Tim-3 expression suggested that Tim-3 expression was positively related to significant immune cell infiltration.
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Neoplasias Encefálicas/metabolismo , Quimiocinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/biossíntese , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Quimiocinas/genética , Bases de Dados Genéticas/tendências , Glioblastoma/diagnóstico , Glioblastoma/genética , Receptor Celular 2 do Vírus da Hepatite A/genética , Humanos , PrognósticoRESUMO
Objectives: To evaluate the safety and efficacy of ultrasound (US)-guided totally implantable venous access ports (TIVAPs) via the right brachiocephalic vein (BCV) or the left BCV approach. Methods: Patients requiring TIVAP for chemotherapy were included in the study. US-guided TIVAPs via BCV were used for patients from July 2018 to December 2018. General information about the patients (sex, age, and diagnosis), side (right or left), surgical procedures and complications were recorded. Results: A total of 107 TIVAPs in 107 patients (ages 38-73 years) were included, 75 via the right BCV and 32 via the left BCV. All of the patients underwent successful surgery. The BCV was successfully punctured on the first attempt in 99 patients (92.52%). Two attempts were needed in 6 patients (5.61%), and three attempts were necessary in 2 patients (1.87%). The mean operation time was 29 ± 5 min (range: 24 to 38 min). No serious complications occurred during the surgery, except the formation of a local haematoma in 1 case after artery puncture. During the follow-up period of 12 months, the incidence of long-term complications was 3.74% (4/107), including 2 cases of catheter-related infection and 2 cases of fibrin sheath formation. No serious complications such as catheter malposition or rupture were found. Conclusion: US-guided TIVAP via the BCV offers an alternative for adults with good needle guidance and a low rate of perioperative and postoperative complications.
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PURPOSE: The totally implantable venous access port (TIVAP) provides patients with safe, effective and long-term convenient venous access for the administration of medications such as chemotherapy drugs. The implantation and long-term use of TIVAP are related to thrombosis, infection and other complications. In this study, the medical records of multicentre patients were collected, and the perioperative and postoperative complications were retrospectively analysed to objectively evaluate the safety of the implantation of supraclavicular, ultrasound-guided TIVAP via the brachiocephalic vein (BCV). PATIENTS AND METHODS: We retrospectively analysed the clinical data of 433 adult patients who had undergone ultrasound-guided TIVAP implantation via the BCV at four hospitals in China from March 2018 to May 2019. The success rates of the first puncture, operation time, and perioperative and postoperative complications were analysed. RESULTS: All the TIVAPs were implanted successfully (100%). The average TIVAP carrying time was 318.15 ±44.22 days (range: 38-502 days) for a total of 197,694 catheter days. The success rate of the first puncture was 94.92% (411/433), and the average operation time was 29.66 ±7.45 min (range: 18-60 min). The perioperative complications included arterial puncture in 4 patients and pneumothorax in 1 patient. The incidence of postoperative complications was 5.08% (22/433), including poor incision healing (n = 2), catheter-related infection (n = 3), port infection (n = 6), thrombosis (n = 2) and fibrin sheath formation (n = 8). Another patient had infusion disturbance 2 days after the operation, and chest X-ray showed bending at the connection between the catheter and port. No other serious complications occurred, such as catheter rupture and drug leakage. The total incidence of complications was 6.24% (27/433). CONCLUSION: This study showed excellent tolerance of supraclavicular, ultrasound-guided BCV puncture to implant TIVAP and a low incidence of complications. As a safe and effective method of TIVAP implantation, it can provide a new choice for clinicians.
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Hyperlipidemia and its associated obesity, hepatic steatosis, and NAFLD are worldwide problems. However, there is no ideal pharmacological treatment for these. Therefore, the complementary therapies that are both natural and safe have been focused. Healthy foods, such as fruit vinegar, may be one of the best choices. In this study, we made a special medicinal fruit vinegar, Schisandra fruit vinegar (SV), and examined its lipid-lowering effects and the underlying mechanisms in a high-fat diet rat model. The results showed that SV significantly reduced the body weight, liver weight, liver index, the serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free fatty acid (FFA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA), increased the content of high-density lipoprotein cholesterol (HDL-C) and the activity of superoxide dismutase (SOD), upregulated the expressions of peroxisome proliferative activated receptor (PPAR-α), peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), and carnitine palmitoyltransferase 1 (CPT1) proteins, increased the contents of key component of antioxidant defense NF-E2-related factor 2 (NRF2) and its downstream heme oxygenase-1 (HO-1) protein, and downregulated the expression of Kelch-like ECH-associated protein 1 (KEAP1). These results suggest that SV has weight loss and lipid-lowering effects in HFD rats, which may be related to its upregulation of the expressions of ß-oxidation -elated PPAR-α, CPT1, and ACOX1 and the regulation of the expressions of antioxidant pathway-related KEAP1-NRF2-HO-1. Therefore, all these data provide an experimental basis for the development of SV as a functional beverage which is safe, effective, convenient, and inexpensive.
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BACKGROUND: Esophageal fistula and stricture is rare but life-threatening complication for esophageal cancer. The management of esophageal fistula and stricture remains challenging. We aimed to determine the safety, feasibility and efficacy of covered metallic stent and three tubes placement for the management of esophageal fistula and stricture. METHODS: Between May 2012 and March 2018, all patients with esophageal fistula and stricture were treated using three tubes or covered metallic stent placement. Patients in group A received covered stents and three tubes placement. Patients in group B only received three tubes placement. Continue abscess drainage and nutritional support was performed after procedure. Three tubes or esophageal stents were removed once esophageal fistula heals. The related medical records were retrospectively assessed. RESULTS: Thirty-seven consecutive patients with esophageal fistula and stricture were enrolled, including 26 patients in group A and 11 patients in group B. Stent placement procedure was technically successful in 25 patients (96.2%). A total of 42 covered stents were inserted. Seventeen esophageal stents were successfully removed from 10 patients. The median retention duration was 3.3 months and 3.4 months for stent and abscess drainage tubes, respectively. One perioperative death due to massive hemorrhage was observed 21 days after stent placement. The abscess cavity was decreased or disappeared in 17 cases and 4 cases in group A and group B, respectively. During follow up, patients in group A still showed a significant better condition of normal diet than that in group B (p < 0.05). Fourteen patients died of cancer recurrence, 3 patients died of massive digestive bleeding and 2 patients died of severe pulmonary infection. The median survivals were 14.8 months and 13.2 months for group A and group B, respectively. CONCLUSIONS: Covered metallic stent placement is safe, feasible and efficacious for treatment of esophageal fistula and stricture, with a better condition of normal diet than patients only received three tubes placement.
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Fístula Esofágica , Neoplasias Esofágicas , Estenose Esofágica , Constrição Patológica , Fístula Esofágica/etiologia , Fístula Esofágica/cirurgia , Neoplasias Esofágicas/complicações , Estenose Esofágica/etiologia , Estenose Esofágica/cirurgia , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to report long-term outcome of superselective embolization in patients with high-flow priapism refractory to medical and surgical treatments. METHODS: From August 2011 until July 2016, 14 patients with high-flow priapism refractory to local treatments were treated and their charts were retrospective reviewed. Clinical evaluation, color Doppler ultrasonography, arteriography and selective embolization were performed. Follow up was performed in all patients. Fourteen men (18-63 years old) were enrolled, with priapism duration of 14 h to 28 days. Internal pudendal arteries or glutaea inferior arteriae were successfully embolized with gelatin sponge particles, polyvinyl alcohol particles or microcoils. RESULTS: Pseudoaneurysm in right femoral artery was found in one case after intervention. The follow-up 1 week later showed that 13 patients were in good condition, the priapism diminished 1-7 days (mean 3.2 ± 0.5 days) after intervention, and 1 patient received second intervention. Mean follow-up was (range 10.8-69.6) months. One patient had recurrent priapism months after embolization and had his penis surgically removed for severe necrosis. CONCLUSIONS: Superselective embolization is safe and effective in high-flow priapism refractory local treatments, with a good long-term prognosis.
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Embolização Terapêutica/métodos , Priapismo/terapia , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Priapismo/fisiopatologia , Priapismo/cirurgia , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The correlation between inflammatory responses caused by spinal cord injury (SCI) and the prognosis of patients with SCI still remains controversial. METHODS: In the present study, we preliminary investigated the serum levels of interleukin (IL)-4, IL-10, major histocompatibility complex (MHC)-I, and inducible nitric oxide synthase (iNOS) and compared the serum IL-4 and IL-10 expression in rats of high Basso-Beattie-Bresnahan (BBB) scores with these of low BBB scores. Besides, the infiltration of macrophage and the axonal regeneration of the injured spinal cord were observed from day 10 to day 30. RESULTS: We found that higher serum levels of IL-4 and IL-10 can reflect the restorability degree of SCI and could be potential biomarkers for the prognosis of SCI. The infiltration of the M2 subtype of macrophage and the axons regrowth might contribute to a better prognosis. CONCLUSIONS: The current study demonstrates that the serum levels of IL-4 and IL-10 are preliminarily adopted as serologic markers to forecast SCI, and high serum levels of IL-4 and IL-10 may indicate a better prognosis. Moreover, the way to promote macrophage polarization from M1 to M2 may contribute to better axonal regeneration.
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Inflamação/sangue , Interleucina-10/sangue , Interleucina-4/sangue , Traumatismos da Medula Espinal/diagnóstico , Animais , Biomarcadores/sangue , Antígenos de Histocompatibilidade Classe I/sangue , Inflamação/diagnóstico , Inflamação/patologia , Masculino , Prognóstico , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/patologia , Fatores de TempoRESUMO
AIM: We report clinical outcomes of transarterial embolization in 19 cases of vaginal cancer. METHODS: From August 2011 to October 2019, 19 patients with histologically diagnosed vaginal cancer were identified in our department. Transarterial chemotherapy and embolization was performed for all patients. Patient characteristics, treatment plans and the clinical outcomes, were recorded. RESULTS: Among 19 identified cases, nine of them are squamous cell carcinoma, five of adenocarcinoma, one of adenosquamous carcinoma, two of vaginal malignant melanoma, one leiomyosarcoma and one of stromal sarcoma. Transarterial chemotherapy and embolization was successfully performed in all patients. No related complication was found after intervention treatment. Besides, eight patients received adjuvant chemotherapy, four received both adjuvant chemotherapy and radiotherapy and seven received no therapies. Four patients were cured and seven were stable during follow-up. CONCLUSION: Transarterial embolization appears safe and effective for vaginal cancer, with a currently acceptable prognosis.
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Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/terapia , Embolização Terapêutica/métodos , Neoplasias Vaginais/terapia , Adenocarcinoma/dietoterapia , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Terapia Combinada/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Vaginais/diagnóstico por imagem , Neoplasias Vaginais/patologiaRESUMO
PURPOSE: A radioactive feeding tube was used to achieve both nutrition and brachytherapy for the treatment for malignant esophageal obstruction. We report the safety and effectiveness of this technique. METHODS: We conducted a retrospective analysis of 16 consecutive patients who employed this technique from January 2015 to March 2018. The radioactive feeding tube was made by binding the 125I seed chain on the feeding tube. Under fluoroscopic guidance, the tube was inserted into the obstructed esophagus, with the seed chain crossing over the segment of malignant esophageal obstruction. Technical success rate, dysphagia score, procedure time and complications were analyzed. Kaplan-Meier analysis was used to analyze the survival time. RESULTS: The radioactive feeding tube was easy to prepare. The technical success rate was 100%, without serious complications such as bleeding or infection. The median procedure time of tube insertion was 44.0 min. The Kamofsky score and Neuhaus dysphagia grading were significantly improved after tube insertion (p < 0.01). On esophageal radiography, the contrast agent passed through the narrow area smoothly. Complete remission (n = 1) and partial remission (n = 13) of local tumor were obtained in 14 patients, and the local tumor control rate was 87.5% (14/16). During follow-up, four patients survived with no obvious clinical symptom and 10 patients died of cancer. The median survival was 12.0 months. CONCLUSION: Preparation of the radioactive feeding tube is simple and easy. The insertion of this kind of tube achieves parenteral nutrition and brachytherapy simultaneously and is safe and effective in dysphagia palliation of malignant esophageal stricture. The radiological-radiotherapeutic procedure could be an alternative tool in the case of refusing other treatments by the patients.
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Braquiterapia , Nutrição Enteral/instrumentação , Estenose Esofágica/terapia , Radioisótopos do Iodo , Cuidados Paliativos/métodos , Idoso , Desenho de Equipamento , Neoplasias Esofágicas/complicações , Estenose Esofágica/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Self-expandable metallic stents (SEMSs) have been widely used in the treatment of malignant central airway obstruction. However, few reports focus on the treatment of atelectasis and how to estimate the prior probability of success via SEMSs placement, This current study aimed to study the safety and effectiveness of SEMSs for the treatment of obstructive atelectasis, and the value of preoperative CT enhancement for ventilation of atelectasis via SEMSs placement. A total of 35 patients with obstructive atelectasis (29 male and 6 female) was included from February 2012 to March 2018. The procedures were performed under fluoroscopic guidance, and bronchoscopic laser resection was performed for severe restenosis cases after SEMSs placement. Clinical and functional pulmonary data were recorded before and 3 months after the procedure. Follow-up involved clinical data and radiographic techniques at 48 h and at 1-, 3-, 6-, and 12-month intervals. Thirty-eight SEMSs were successfully implanted in 34 patients, included 29 Y type tracheal stents, 4 small y stents, and 5 straight airway stents. After stenting, 26 cases showed full ventilation, and 3 cases were partially ventilated. The technical success and clinical success was 97.1% and 82.9%, respectively. A higher maximum enhancement CT value was found in patients with full ventilation. Mean follow-up time was 18.8 ± 4.0 months. Eight cases showed restenosis and received endoscopic laser resection, included 1 case underwent removal and 3 cases received second stenting. There were 2 cases of perioperative non-operative death, and 11 cases of post-discharge death (2 cardiac deaths and 9 malignant tumors). The survival rates of 3 months, 1 year and 2 years were 78.6%, 58.5% and 58.5%, respectively. In conclusion, SEMSs placement is safe and effective for obstructive atelectasis, and the preoperative CT enhancement played an important role in estimating the prior probability of success in the treatment of atelectasis via SEMSs placement.
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Obstrução das Vias Respiratórias/prevenção & controle , Neoplasias Pulmonares/terapia , Pulmão/patologia , Implantação de Prótese , Stents Metálicos Autoexpansíveis , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/mortalidade , Feminino , Seguimentos , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Atelectasia Pulmonar , Testes de Função Respiratória , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Aging is a spontaneous and inevitable phenomenon of biology, which can lead to the gradual deterioration of tissues and organs. One of the age-related deterioration processes is immunosenescence, which leads to changes in the function of immune systems, including immune cells and associated cytokines. A proper modulation of immune responses can improve the age-related immunosenescence process and then reach healthy aging. Schisandra sphenanthera, a traditional Chinese medicine, has been used as both a medicine and a nutritional supplement for thousands of years. Anwulignan, a monomer compound of Schisandra sphenanthera lignans, has been reported to possess an immunomodulatory effect. Therefore, this study was designed to further explore whether Anwulignan could also modulate the immune functions in aging model mice and the underlying mechanism. METHODS: D-galactose (D-gal) is often used as an inducer of immunosenescence in animals. In this study, a mice model was created by subcutaneous D-gal (220 mg kg-1) for successive 42 days. Then, the blood and spleen tissue samples were taken for the analysis and observation of cytokine levels, immunoglobulin levels, leukocyte numbers, and the phagocytic activity of macrophages, as well as the histological changes, the proliferation ability of lymphocytes, and the biochemical parameters in the spleen tissue. RESULTS: Anwulignan significantly increased the serum levels of IL-2, IL-4, IFN-γ, lgG, lgM, and lgA, decreased the content of TNF-α and IL-6 in the aging mice, and increased the blood leukocyte number, the phagocytic activity, the lymphocyte proliferation, and the spleen index in vitro. Anwulignan also significantly increased the activities of SOD and GSH-Px, decreased the contents of MDA and 8-OHdG in the spleen tissue, up-regulated the expressions of Nrf2, HO-1, and Bcl2, down-regulated the expressions of Keap1, Caspase-3, and Bax in the spleen cells, and reduced the apoptosis of spleen lymphocytes. CONCLUSION: Anwulignan can restore the immune function that is declined in D-gal-induced aging mice partly related to its antioxidant capacity by activating the Nrf2/ARE pathway and downstream enzymes, as well as its anti-apoptotic effect by regulating Caspase-3 and the ratio of Bcl2 to Bax in the spleen.
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Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Imunossenescência , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Schisandra , Animais , Antioxidantes/farmacologia , Citocinas/classificação , Fatores Imunológicos/farmacologia , Imunossenescência/efeitos dos fármacos , Imunossenescência/fisiologia , Masculino , Medicina Tradicional Chinesa/métodos , Camundongos , Modelos Animais , Compostos Fitoquímicos/farmacologia , Baço/imunologiaRESUMO
To study the safety and efficacy of fluoroscopic removal of self-expandable metallic stent for airway stenosis.We conducted a retrospective analysis of 67 consecutive patients, 39 male and 28 female, who underwent fluoroscopic stent removal from March 2011 to April 2017. The patients ranged in age from 12 to 85 years. Seventy-six airway stents were implanted, 70 covered stents and 6 bare stents, including 9 stents for second stent implantation after removal. All patients underwent chest computed tomography scans with/without bronchoscopy before stent removal. The indication of stent removal and postinterventional complications were analyzed retrospectively.Seventy-four of 76 airway stents were successfully removed, only 2 stent showed retained struts after removal, for a technical success rate of 97.4%. Two patients died of complications (1 hemorrhage and 1 respiratory failure), resulting in a clinical success rate of 94.7%. Five stents showed strut fracture and the remaining 71 stents were removed in 1 piece. Indications for stent removal include planned removal (n = 40), excessive granulation tissue (nâ=â15), intolerance of stenting (nâ=â6), inadequate expansion and deformation (nâ=â5), stent migration (nâ=â5), replacement of bare stent (nâ=â4), and strut fracture (nâ=â1). There were 17 complications of stent removal: death from massive bleeding (nâ=â1), restenosis requires stenting (nâ=â9), strut fracture or residue (nâ=â5), dyspnea requires mechanical ventilation (nâ=â2). The survival rates were 83.8%, 82.1%, and 82.1% for 0.5, 3, and 6 years.Fluoroscopic removal of airway stent is technically feasible and effective. Stents are recommended for removal within 3 months for treating airway stenosis.
Assuntos
Broncopatias/terapia , Remoção de Dispositivo/métodos , Radiografia Intervencionista/mortalidade , Stents , Estenose Traqueal/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Remoção de Dispositivo/mortalidade , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Synovial mesenchymal stem cells (SMSCs) with high proliferation and multi differentiation ability, and low immunogenicity have attracted research attention for their potential application in tissue engineering. Once their ability of osteogenesis is strengthened, it will be of practical value to apply the SMSCs in the field of bone regeneration. The current study aimed to investigate the osteogenic characteristics of SMSCs induced by bone morphogenetic protein 9 (BMP9) both in vitro and in vivo and to elucidate the mechanism underlying these characteristics. Specifically, different BMPs were assessed to determine the protein that would be the most favorable for stimulating osteogenic differentiation of SMSCs following their separation. The BMP9-enhanced osteogenesis of SMSCs was fully investigated in vitro and in vivo, and the c-Jun N-terminal kinase (JNK)/Smad2/3 signaling pathway stimulated by BMP9 was further explored. Our data suggested that BMP9 could significantly promote gene and protein expression of runt-related transcription factor 2, alkaline phosphatase, osteopontin, and osteocalcin, and SP600125, a JNK-specific inhibitor, could effectively decrease this tendency. Similar results were also confirmed in rats with cranial defects. In conclusion, our study indicated that BMP9 promotes bone formation both in vitro and in vivo possibly by activating the JNK/Smad2/3 signaling pathway.