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The total occlusion of radial artery is a contraindication for reintervention and further usage. In this study, we report successful revascularization with creation of radiocephalic fistula from post-procedural chronically-occluded radial artery. The completely occluded radial artery was recanalized through ultrasound guided balloon angioplasty. A traditional radiocephalic fistula was created subsequently by using the recanalized radial artery for hemodialysis therapy. Though the fistula was failed at the 6 weeks caused by the juxta anastomotic stenosis, the further ultrasound guided percutaneous transluminal angioplasty restored the blood, and the hemodialysis therapy lasts for more than 1 year so far. It's feasible to create radiocephalic fistula based on the recanalized radial artery and maintain long-term hemodialysis therapy.
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OBJECTIVES: Ultrasonography is more frequently used in patients with arteriovenous fistula (AVF) stenosis. The aim of this study is to use sonographic parameters for predicting primary patency in hemodialysis patients with venous valve-related stenosis (VVRS) who are treated by ultrasound-guided percutaneous transluminal angioplasty (PTA). METHODS: A total of 229 VVRS patients who underwent PTA between January 2017 and December 2021 were enrolled. Clinical characteristics were retrospectively collected. Sonographic parameters were measured both before and after PTA. Univariate and multivariate Cox analyses were performed to identify independent factors associated with primary patency rate. RESULTS: All measured sonographic parameters improved after PTA compared to before PTA. Before PTA, the diameter of VVRS > 1.0 mm, age ≤ 57 years, and body mass index (BMI) > 21.57 kg/m2 were associated with better outcomes. While the diameter of radial artery, proximal radial artery close to the anastomosis, brachial artery, the flow volume of brachial artery, the length and peak velocity (PV) of the VVRS, and the diameter and PV after the VVRS had no association with the primary patency rate. After PTA, only patients with a diameter of VVRS > 4.0 mm had favorable outcome. In addition, patients with a gain of diameter of VVRS > 2.4 mm after PTA had a trend of better outcomes. CONCLUSIONS: The diameter of VVRS before and after PTA could be served as markers to predict primary patency rate and second patency rate in AVF patients with VVRS. The gain of diameter of VVRS could also be a potential marker. CLINICAL IMPACT: Using simple markers of sonographic parameters, we could quickly identify patients with a higher risk of restenosis. These patients should be followed more closely in case of restenosis at early. It is also beneficial to the prevention of thrombosis. These measures help to preserve more valuable vascular for a long-term dialysis. Additionally, the physician should pay more attention on the dialysis-related complications in these risky patients, such as hemodialysis-related hypotension.
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Efferocytosis, the clearance of apoptotic cells by macrophages, plays a crucial role in inflammatory responses and effectively prevents secondary necrosis. However, the mechanisms underlying efferocytosis in acute pancreatitis (AP) remain unclear. In this study, we demonstrated the presence of efferocytosis in injured human and mouse pancreatic tissues. We also observed significant upregulation of CD47, an efferocytosis-related the "do not eat me" molecule in injured acinar cells. Subsequently, we used CRISPR-Cas9 gene editing, anti-adeno-associated virus (AAV) gene modification, and anti-CD47 antibody to investigate the potential therapeutic role of AP. CD47 expression was negatively regulated by upstream miR133a, which is controlled by the transcription factor TRIM28. To further investigate the regulation of efferocytosis and reduction of pancreatic necrosis in AP, we used miR-133a-agomir and pancreas-specific AAV-shTRIM28 to modulate CD47 expression. Our findings confirmed that CD47-mediated efferocytosis is critical for preventing pancreatic necrosis and suggest that targeting the TRIM28-miR133a-CD47 axis is clinically relevant for the treatment of AP.
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Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (P = 0.048) and 96 (P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010-37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770).Trial registration: ClinicalTrials.gov identifier: NCT04098770.Trial registration: ClinicalTrials.gov identifier: NCT02651376.
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Hospedeiro Imunocomprometido , Imunoterapia Adotiva , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Imunoterapia Adotiva/métodos , Antígenos HLA/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Resultado do Tratamento , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Transplante Homólogo , Linfócitos T CD4-Positivos/imunologia , Contagem de Linfócito CD4RESUMO
Introduction: Venous valve-related stenosis (VVRS) is an uncommon type of failure of arteriovenous fistula among patients with end-stage renal disease (ESRD). There is a paucity of data on the long-term efficacy of ultrasound-guided percutaneous transluminal angioplasty (PTA) for VVRS. Methods: ESRD patients who underwent PTA because of VVRS between January 2017 and December 2021 at the First Affiliated Hospital of Chongqing Medical University were enrolled. Patients were classified into three cohorts (cohort1, VVRS located within 3 cm of the vein adjacent to the anastomosis; cohort2, VVRS located over 3 cm away from the anastomosis; cohort3, multiple stenoses). The patency rates were assessed by the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox analyses were performed to identify the risk factors. Results: A total of 292 patients were enrolled, including 125 (42.8%), 111 (38.0%), and 56 (19.2%) patients in cohort1, cohort2, and cohort3, respectively. The median follow-up was 34.8 months. The 6-month, 1-year, 2-year, and 3-year primary patency rates were 86.0%, 69.4%, 47.5%, and 35.3%, respectively. The secondary patency rates were 94.5%, 89.4%, 75.5%, and 65.3%, respectively. Cohort1 showed a relatively better primary patency compared to cohort2 and cohort3. The secondary patency rates were comparable in the three cohorts. Duration of dialysis and VVRS type were potential factors associated with primary patency. Conclusions: This study showed acceptable long-term primary and secondary patency rates after PTA for VVRS in ESRD patients, especially for those with VVRS located within 3 cm of the vein adjacent to the anastomosis.
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Precision and intelligence in evaluating the complexities of middle ear structures are required to diagnose auriculotemporal and ossicle-related diseases within otolaryngology. Due to the complexity of the anatomical details and the varied etiologies of illnesses such as trauma, chronic otitis media, and congenital anomalies, traditional diagnostic procedures may not yield accurate diagnoses. This research intends to enhance the diagnosis of diseases of the auriculotemporal region and ossicles by combining High-Resolution Spiral Computed Tomography (HRSCT) scanning with Deep Learning Techniques (DLT). This study employs a deep learning method, Convolutional Neural Network-UNet (CNN-UNet), to extract sub-pixel information from medical photos. This method equips doctors and researchers with cutting-edge resources, leading to groundbreaking discoveries and better patient healthcare. The research effort is the interaction between the CNN-UNet model and high-resolution Computed Tomography (CT) scans, automating activities including ossicle segmentation, fracture detection, and disruption cause classification, accelerating the diagnostic process and increasing clinical decision-making. The suggested HRSCT-DLT model represents the integration of high-resolution spiral CT scans with the CNN-UNet model, which has been fine-tuned to address the nuances of auriculotemporal and ossicular diseases. This novel combination improves diagnostic efficiency and our overall understanding of these intricate diseases. The results of this study highlight the promise of combining high-resolution CT scanning with the CNN-UNet model in otolaryngology, paving the way for more accurate diagnosis and more individualized treatment plans for patients experiencing auriculotemporal and ossicle-related disruptions.
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Ossículos da Orelha , Tomografia Computadorizada Espiral , Humanos , Tomografia Computadorizada Espiral/métodos , Ossículos da Orelha/diagnóstico por imagem , Aprendizado Profundo , Otopatias/diagnóstico por imagem , Osso Temporal/diagnóstico por imagem , Adulto , Redes Neurais de ComputaçãoRESUMO
The edible fungus industry is one of the pillar industries in the Yunnan-Guizhou Plateau, China. The expansion of the planting scale has led to the release of various mushroom residues, such as mushroom feet, and other wastes, which are not treated adequately, resulting in environmental pollution. This study investigated the ability of black soldier fly (Hermetia illucens L.) larvae (BSFL) to degrade mushroom waste. Moreover, this study analyzed changes in the intestinal bacterial community and gene expression of BSFL after feeding on mushroom waste. Under identical feeding conditions, the remaining amount of mushroom waste in Pleurotus ostreatus treatment group was reduced by 18.66%, whereas that in Flammulina velutipes treatment group was increased by 31.08%. Regarding gut microbial diversity, compared with wheat bran-treated control group, Dysgonomonas, Providencia, Enterococcus, Pseudochrobactrum, Actinomyces, Morganella, Ochrobactrum, Raoultella, and Ignatzschineria were the most abundant bacteria in the midgut of BSFL in F. velutipes treatment group. Furthermore, Dysgonomonas, Campylobacter, Providencia, Ignatzschineria, Actinomyces, Enterococcus, Morganella, Raoultella, and Pseudochrobactrum were the most abundant bacteria in the midgut of BSFL in P. ostreatus treatment group. Compared with wheat bran-treated control group, 501 upregulated and 285 downregulated genes were identified in F. velutipes treatment group, whereas 211 upregulated and 43 downregulated genes were identified in P. ostreatus treatment group. Using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we identified 14 differentially expressed genes (DEGs) related to amino sugar and nucleotide sugar metabolism in F. velutipes treatment group, followed by 12 DEGs related to protein digestion and absorption. Moreover, in P. ostreatus treatment group, two DEGs were detected for fructose and mannose metabolism, and two were noted for fatty acid metabolism. These results indicate that feeding on edible mushroom waste can alter the intestinal microbial community structure of BSFL; moreover, the larval intestine can generate a corresponding feedback. These changes contribute to the degradation of edible mushroom waste by BSFL and provide a reference for treating edible mushroom waste using BSFL.
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Agaricales , Microbioma Gastrointestinal , Larva , Pleurotus , Animais , Larva/microbiologia , Pleurotus/metabolismo , Agaricales/metabolismo , Agaricales/genética , Biodegradação Ambiental , Dípteros/microbiologia , Dípteros/metabolismo , Flammulina/metabolismo , Flammulina/genética , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificaçãoRESUMO
BACKGROUND: Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era. METHODS: An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits. RESULTS: A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P < 0.05), and the improvement in the FEV1/FVC was significantly greater than that in the NICS group (P = 0.003) after 60 days. CONCLUSIONS: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may contribute to the pathogenesis of asthma, which could be the underlying cause of persistent cough post-COVID-19 infection. Post-COVID-19 chronic cough during the Omicron era was often accompanied by sputum, dyspnea, and airway hyperresponsiveness. ICS treatment did not have a significant impact on symptom management of post-COVID-19 chronic cough; however, it can improve impaired lung function in in these individuals.
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Asma , COVID-19 , Humanos , Tosse Crônica , Estudos Longitudinais , COVID-19/complicações , SARS-CoV-2 , Asma/complicações , Asma/tratamento farmacológico , Corticosteroides/uso terapêutico , Tosse , Dispneia/tratamento farmacológico , Administração por InalaçãoRESUMO
Persicaria capitata was a frequently used Hmong medicinal flora in China. In this study, one new phenolic compound, capitaone A (1) together with 20 known ones, were isolated from the whole herb of P. capitata. Among them, 7 components (4, 9-11, 15-16, 20-21) were discovered from P. capitata for the first time. Their chemical structures were elucidated on the basis of extensive NMR and MS spectrum. Furthermore, three compounds (15, 20, 21) displayed remarkable cytotoxic activities against two human cancer cell lines (A549 and HepG2).
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Acute upper limb ischemia is a rare, potentially limb- or life-threatening vascular emergency that may lead to limb dysfunction or amputation. We present a patient undergoing maintenance hemodialysis who was hospitalized for arteriovenous graft thrombus complicated by acute upper limb ischemia arising from thrombus shedding to the fingertip arteries during thrombolysis. We successfully restored fingertip arterial patency, avoided amputation, and recovered the function of the arteriovenous graft by precise thrombolysis, anticoagulation, correction of arteriospasm, and percutaneous transluminal angioplasty. This case provides a basis for vascular access surgeons to treat acute upper limb ischemia caused by thromboembolism similarly.
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Diálise Renal , Trombose , Humanos , Isquemia/etiologia , Trombose/tratamento farmacológico , Trombose/etiologia , Terapia Trombolítica , Resultado do Tratamento , Grau de Desobstrução Vascular , Estudos RetrospectivosRESUMO
OBJECTIVE: Human adenovirus (HAdV) infection is common and can develop to serious conditions with high mortality, yet the mechanism of HAdV infection remains unclear. In the present study, the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection (URTI) were explored. METHODS: In total, 35 patients were enrolled in the study following an outbreak of HAdV-7 in the army, of whom 14 had pneumonia and 21 had URTI. Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics. RESULTS: Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules, including glycerophospholipids, fatty acyls, and sphingolipids. The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways, including sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients, but not between the acute and recovery stages for the URTI patients. Ceramide and lactosylceramide, involved in sphingolipid metabolism, were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities [area under curve (AUC) 0.742 and 0.716, respectively; combination AUC 0.801]. CONCLUSION: Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia, especially the sphingolipid metabolism involving ceramide and lactosylceramide, which might thus be a potential intervention target in the treatment of HAdV infection.
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Infecções por Adenovirus Humanos , Adenovírus Humanos , Antígenos CD , Pneumonia , Infecções Respiratórias , Humanos , Adenovírus Humanos/genética , Lactosilceramidas , Infecções Respiratórias/epidemiologia , Pneumonia/complicações , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/metabolismoRESUMO
Bile acids are altered and associated with prognosis in patients with acute pancreatitis (AP). Here, we conduct targeted metabolomic analyses to detect bile acids changes in patients during the acute (n = 326) and the recovery (n = 133) phases of AP, as well as in healthy controls (n = 60). Chenodeoxycholic acid (CDCA) decreases in the acute phase, increases in the recovery phase, and is associated with pancreatic necrosis. CDCA and its derivative obeticholic acid exhibit a protective effect against acinar cell injury in vitro and pancreatic necrosis in murine models, and RNA sequencing reveals that the oxidative phosphorylation pathway is mainly involved. Moreover, we find that overexpression of farnesoid X receptor (FXR, CDCA receptor) inhibits pancreatic necrosis, and interfering expression of FXR exhibits an opposite phenotype in mice. Our results possibly suggest that targeting CDCA is a potential strategy for the treatment of acinar cell necrosis in AP, but further verification is needed.
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Ácidos e Sais Biliares , Pancreatite Necrosante Aguda , Humanos , Camundongos , Animais , Pancreatite Necrosante Aguda/tratamento farmacológico , Doença Aguda , Receptores Citoplasmáticos e Nucleares , Ácido Quenodesoxicólico/farmacologia , Ácido Quenodesoxicólico/uso terapêuticoRESUMO
Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9's production. Using an orthotopic mouse model of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in bidirectional crosstalk between pancreatic tumor epithelium and TME and results in a pro-|tumorigenic contexture.
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Fibroblastos Associados a Câncer , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Camundongos , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Epitélio/metabolismo , Fibroblastos/metabolismo , Neoplasias Pancreáticas/patologia , Pró-Proteína Convertase 9/metabolismo , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
BACKGROUND AND AIMS: The microbial spectrum and antimicrobial resistance patterns change over time and vary across regions in patients with spontaneous bacterial peritonitis (SBP). There is an urgent need to clarify the factors associated with in-hospital mortality in these patients. METHODS: In this study, 377 patients with SBP and 794 patients with bacterascites were analyzed for the microbial spectrum, antimicrobial resistance profiles, and laboratory findings. RESULTS: The most common pathogens were Escherichia coli (96, 25.5%), Staphylococcus epidermidis (55, 14.6%), and Enterococcus faecium (42, 11.1%). Multidrug-resistant (MDR) bacteria comprised 49.7% of gram-positive bacteria (GPB) and 48.8% of gram-negative bacteria (GNB). The most sensitive antibiotics were amikacin (91.5%), meropenem (89.8%) and piperacillin/tazobactam (87.6%). Extensively drug-resistant (XDR) (OR=51.457, p < 0.001), neutrophil count (OR=1.088, p < 0.001), and the model for end-stage liver disease (MELD) score (OR=1.124, p < 0.001) were independent predictive factors of in-hospital mortality in patients with SBP. CONCLUSION: MDR represented nearly half of the bacteria isolated from patients with SBP, of which the high prevalence of extended-spectrum ß-lactamase-producing and Carbapenem-resistant bacteria is concerning. The presence of XDR, higher MELD score, and neutrophil count were independent predictive factors associated with higher in-hospital mortality in patients with SBP, indicating that intensive care should be provided to these patients.
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Doença Hepática Terminal , Peritonite , Humanos , Doença Hepática Terminal/complicações , Cirrose Hepática/complicações , Índice de Gravidade de Doença , Peritonite/tratamento farmacológico , Antibacterianos/uso terapêutico , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVE: The effectiveness and security of radiofrequency ablation (RFA) in combination with toripalimab (anti-PD-1) for the treatment of recurrent hepatocellular carcinoma (HCC) was studied in this article. METHODS: Total of 40 patients were enrolled in the study between September 2019 and November 2021. Data follow-up ends in April 2022. The study's main focus is on recurrence free survival (RFS), while the secondary objectives was safety. Chi-square tests, Kaplan-Meier, and Cox proportional hazards models were utilized to analyze the data. RESULTS: The median follow-up period was 21.40 months, and the median RFS was 15.40 months in the group that received combination therapy, which was statistically significantly different (HR: 0.44, p = 0.04) compared with the RFA group (8.2 months). RFS rates (RFSr) at 6, 12 and 18 months in the combination therapy groups and RFA groups were 80% vs 65%, 62.7% vs 35% and 48.7% vs 18.8%, respectively. Between the two groups, significant difference of RFSr was found at 18 months (p = 0.04). No statistical differences were observed between the two groups in terms of safeness (p > 0.05). The subgroup analysis indicated that the combination of RFA and anti-PD-1 led to better RFS than RFA alone. Moreover, patients benefited more from combination therapy in the groups younger than 60 years (HR: 0.26, p = 0.018), male (HR: 0.32, p = 0.028) and Child-Pugh grade A (HR: 0.38, p = 0.032). CONCLUSIONS: Combining RFA with anti-PD-1 showed improved RFS and was deemed safe for patients with recurrent HCC who had previously undergone RFA treatment alone.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Masculino , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Feminino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Identifying a metastasis-correlated immune cell composition within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) will help to develop promising and innovative therapeutic strategies. However, the dynamics of immune cell lineages in the TME of advanced PDAC remains elusive. METHODS: Twenty-six samples from 11 patients (including 11 primary tumor tissues, 10 blood, and 5 lymph nodes) with different stages were used to develop a multiscale immune profile. High-dimensional single-cell analysis with mass cytometry was performed to search for metastasis-correlated immune changes in the microenvironment. The findings were further validated by published single-cell RNA sequencing (scRNA-seq) data and multiplex fluorescent immunohistochemistry. FINDINGS: High-dimensional single-cell profiling revealed that the three immune-relevant sites formed a distinct immune atlas. Interestingly, the PDAC microenvironment with the potential for metastatic spread to the liver was characterized by a decreased proportion of CD103+PD-1+CD39+ T cells with cytotoxic and exhausted functional status and an increased proportion of CD73+ macrophages. Analysis of scRNA-seq data of PDAC further confirmed the identified subsets and revealed strong potential interactions via various ligand-receptor pairs between the identified T subsets and the macrophages. Moreover, stratified patients with different immune compositions correlated with clinical outcomes of PDAC. CONCLUSIONS: Our study uncovered metastasis-correlated immune changes, suggesting that ecosystem-based patient classification in PDAC will facilitate the identification of candidates likely to benefit from immunotherapy. FUNDING: This work was supported by the National Key Research and Development Program of China, the Shanghai International Science and Technology Collaboration Program, the Shanghai Sailing Program, and the Key Laboratory of diagnosis and treatment of severe hepato-pancreatic diseases of Zhejiang Province.
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Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Ecossistema , China , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
BACKGROUND: To investigate the clinical outcomes of indwelling needle-delivered local urokinase thrombolysis, a cost-saving thrombolytic approach, in the treatment of thrombosed arteriovenous grafts (AVGs). METHODS: The clinical data of 71 patients with a first episode of thrombosed AVG were analyzed. Among them, 49 patients underwent urokinase thrombolysis and percutaneous transluminal angioplasty (PTA), and 22 patients underwent thrombectomy and PTA. The operation success rate, operation time, perioperative and postoperative complications, primary patency, and secondary patency were compared. RESULTS: Clinical success was achieved in all 71 PTAs. After thrombolysis, 29 patients achieved complete lysis, and 20 patients achieved partial lysis. All patients achieved thrombus clearance after PTA. The operating room usage time was 37.48 ± 5.33 min for the complete thrombolysis group and 41.70 ± 6.16 min for the incomplete thrombolysis group, and these values were not significantly different (p = 0.853). The operating room usage time of the thrombectomy group was 124.73 ± 5.08 min, which was significantly longer than that of the other groups (p < 0.001). The log-rank test indicated no significant difference in the 90-, 180-, and 360-day primary patency and corresponding secondary patency (all p > 0.05). The Cox regression showed that no significant difference was noted in the changing rate of primary or secondary patency among the groups (all p > 0.05). No major complications occurred in any of the groups, and the difference in the complication incidence was not significant (p = 0.336). CONCLUSIONS: Indwelling needle-delivered urokinase thrombolysis is an acceptable method for the treatment of thrombosed AVGs. Compared with thrombectomy and PTA, thrombolysis and PTA can significantly shorten the time to use the operating room without reducing primary and secondary patency or increasing complications.
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BACKGROUND: Left brachiocephalic vein (LBCV) stenosis is a common complication in hemodialysis patients and is a heterogenous disorder associated with either prior catheterization or extrinsic compression. This study aimed to characterize patients with LBCV stenosis or occlusion with and without a history of central venous catheterization. METHODS: We performed a retrospective study in 84 hemodialysis patients with LBCV stenosis or occlusion with (n = 22) or without (n = 62) prior catheterization. We compared the clinical features, anatomical factors, restenosis after balloon venoplasty, and patency rates of patients in these two groups. RESULTS: In the cohort of 84 patients with LBCV stenosis or occlusion, 73.8% (62 patients) of them had no history of catheterization. Patients without prior catheterization had more stenotic lesions (p < 0.05) but less occlusive lesions (p < 0.05) than patients with prior catheterization. The space between the sternum and the aorta was narrower in patients without prior catheterization than that in patients with prior catheterization (p < 0.05). Percutaneous venography was performed in 81 patients, and the occurrence of recoil after venoplasty in patients without prior catheterization was significantly higher than that in patients with prior catheterization (p < 0.05). The rate of stent implantation was significantly higher in patients without prior catheterization than patients with prior catheterization (p < 0.05), whereas there was no significant difference in primary patency between the two groups. CONCLUSIONS: LBCV stenosis and occlusion are mainly due to extrinsic compression rather than prior central venous catheterization. Stent implantation is frequently required after venoplasty to treat LBCV obstructive lesions in patients without prior catheterization.
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DNA damage repair (DDR) is a double-edged sword with different roles in cancer susceptibility and drug resistance. Recent studies suggest that DDR inhibitors affect immune surveillance. However, this phenomenon is poorly understood. We report that methyltransferase SMYD2 plays an essential role in nonhomologous end joining repair (NHEJ), driving tumor cells adaptive to radiotherapy. Mechanically, in response to DNA damage, SMYD2 is mobilized onto chromatin and methylates Ku70 at lysine-74, lysine-516, and lysine-539, leading to increased recruitment of Ku70/Ku80/DNA-PKcs complex. Knockdown of SMYD2 or its inhibitor AZ505 results in persistent DNA damage and improper repair, which sequentially leads to accumulation of cytosolic DNA, and activation of cGAS-STING pathway and triggers antitumor immunity via infiltration and activation of cytotoxic CD8+ T cells. Our study reveals an unidentified role of SMYD2 in regulating NHEJ pathway and innate immune responses, suggesting that SMYD2 is a promising therapeutic target for cancer treatment.