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PURPOSE: To assess the efficacy and safety of concurrent hypofractionated radiotherapy plus anti-PD-1 antibody and SOX chemotherapy in the treatment of metastatic pancreatic cancer (mPC) after failure of first-line chemotherapy. METHODS: Patients with pathologically confirmed mPC who failed standard first-line chemotherapy were enrolled. The patients were treated with a regimen of hypofractionated radiotherapy, SOX chemotherapy, and immune checkpoint inhibitors at our institution. We collected the patients' clinical information and outcome measurements. The median progression-free survival (mPFS) was the primary endpoint of the study, followed by disease control rate (DCR), objective response rate (ORR), median overall survival (mOS) and safety. Exploratory analyses included biomarkers related to the benefits. RESULTS: Between February 24, 2021, and August 30, 2023, twenty-five patients were enrolled in the study, and twenty-three patients who received at least one dose of the study agent had objective efficacy evaluation. The mPFS was 5.48 months, the mOS was 6.57 months, and the DCR and ORR were 69.5% and 30.4%, respectively. Among the seven patients who achieved a PR, the median duration of the response was 7.41 months. On-treatment decreased serum CA19-9 levels were associated with better overall survival. Besides, pretreatment inflammatory markers were associated with tumor response and survival. CONCLUSIONS: Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with these combination therapies in patients with refractory mPC. On-treatment decreased serum CA19-9 levels and pretreatment inflammatory markers platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) might be biomarkers related to clinical benefits. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=130211 , identifier: ChiCTR2100049799, date of registration: 2021-08-09.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Hipofracionamento da Dose de Radiação , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Inibidores de Checkpoint Imunológico/uso terapêutico , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Quimiorradioterapia/métodos , Tegafur/uso terapêutico , Tegafur/administração & dosagem , Gencitabina , Metástase NeoplásicaRESUMO
Hydrogels are extensively explored as biomaterials for tissue scaffolds, and their controlled fabrication has been the subject of wide investigation. However, the tedious mechanical property adjusting process through formula control hindered their application for diverse tissue scaffolds. To overcome this limitation, we proposed a two-step process to realize simple adjustment of mechanical modulus over a broad range, by combining digital light processing (DLP) and post-processing steps. UV-curable hydrogels (polyacrylamide-alginate) are 3D printed via DLP, with the ability to create complex 3D patterns. Subsequent post-processing with Fe3+ ions bath induces secondary crosslinking of hydrogel scaffolds, tuning the modulus as required through soaking in solutions with different Fe3+ concentrations. This innovative two-step process offers high-precision (10 µm) and broad modulus adjusting capability (15.8-345 kPa), covering a broad range of tissues in the human body. As a practical demonstration, hydrogel scaffolds with tissue-mimicking patterns were printed for cultivating cardiac tissue and vascular scaffolds, which can effectively support tissue growth and induce tissue morphologies.
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Hidrogéis , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Alicerces Teciduais/química , Hidrogéis/química , Engenharia Tecidual/métodos , Humanos , Alginatos/química , Materiais Biocompatíveis/química , Resinas Acrílicas/química , Módulo de Elasticidade , LuzRESUMO
Introduction: Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, can stimulate erythropoiesis. Our objective was to evaluate the efficacy and safety of roxadustat for the treatment of posttransplantation anemia (PTA). Methods: A total of 150 adult renal transplant recipients who underwent PTA were randomized to either the experimental group or the control group. During the 12-week randomized phase, the experimental group was randomized to oral iron and roxadustat treatment, and the control group was randomized to oral iron treatment only. The randomized phase was followed by a 12-week extended treatment period in which all participants were prescribed roxadustat treatment according to hemoglobin (Hb) levels. All the participants were followed-up with every 4 weeks. The primary end points were the change in Hb levels and response rate throughout the randomized period. Results: A total of 128 participants completed the randomized treatment period (90 in the experimental group and 38 in the control group). The mean Hb concentration at week 12 was 12.20 g/dl in the experimental group and 11.19 g/dl in the control group. A significantly higher proportion of participants who achieved Hb responses were in the experimental group than in the control group. Differences in serum iron, total iron-binding capacity (TIBC) and transferrin from baseline to week 8 to 12 were significant between the 2 groups. The adverse event profiles were comparable between the 2 groups. Conclusion: Roxadustat increased Hb in adult renal transplant recipients who underwent PTA, with an adverse event profile comparable to that of the control group.
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PURPOSE: To establish and validate novel predictive models for predicting bone metastasis (BM) in newly diagnosed prostate adenocarcinoma (PCa) via single-photon emission computed tomography radiomics. METHOD: In a retrospective review of the clinical single-photon emission computed tomography (SPECT) database, 176 patients (training set: n = 140; validation set: n = 36) who underwent SPECT/CT imaging and were histologically confirmed to have newly diagnosed PCa from June 2016 to June 2022 were enrolled. Radiomic features were extracted from the region of interest (ROI) in a targeted lesion in each patient. Clinical features, including age, total prostate-specific antigen (t-PSA), and Gleason grades, were included. Statistical tests were then employed to eliminate irrelevant and redundant features. Finally, four types of optimized models were constructed for the prediction. Furthermore, fivefold cross-validation was applied to obtain sensitivity, specificity, accuracy, and area under the curve (AUC) for performance evaluation. The clinical usefulness of the multivariate models was estimated through decision curve analysis (DCA). RESULTS: A radiomics signature consisting of 27 selected features which were obtained by radiomics' LASSO treatment was significantly correlated with bone status (P < 0.01 for both training and validation sets). Collectively, the models showed good predictive efficiency. The AUC values ranged from 0.87 to 0.98 in four models. The AUC values of the human experts were 0.655 and 0.872 in the training and validation groups, respectively. Most radiomic models showed better diagnostic accuracy than human experts in the training and validation groups. DCA also demonstrated the superiority of the radiomics models compared to human experts. CONCLUSION: Radiomics models are superior to humans in differentiating between benign bone and prostate cancer bone metastases; it can be used to facilitate personalized prediction of BM in newly diagnosed PCa patients.
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PURPOSE: Reducing operative injuries is important in living donor nephrectomy. The robot-assisted transperitoneal approach has some advantages than traditional laparoscopic techniques. However, longer operation time and risks of abdominal complications indicate the need for improved techniques. The aim of this study is to present the robot-assisted laparoscopic retroperitoneal donor nephrectomy and evaluate its safety and feasibility. METHODS: This was a retrospective study. From June 2016 to December 2020, 218 living donors underwent robot-assisted laparoscopic retroperitoneal donor nephrectomy. Perioperative data such as operation time, warm ischemia time, length of stay and complications were collected and analyzed. To evaluate the feasibility of this surgical technique, the cumulative summation method was used to construct a learning curve. RESULTS: There were 60 male and 158 female donors aged 36-72 years, with an average age of 53.1 ± 6.8 years. Three patients (1.4%) were converted to open surgery. The mean operation time was 115.4 ± 41.9 min, the warm ischemia time was 206.6 ± 146.7 s, and the length of stay was 4.1 ± 1.4 days. Complications were reported in 22 patients (10.1%), three of whom (1.4%) had ClavienâDindo IIIa complications. No ileus occurred. No donors were readmitted. Four patients had delayed graft function. The cumulative summation curve showed that the number needed to reach proficiency was 33. The operation time and warm ischemia time after technical proficiency were 100.4 ± 21.6 min and 142.5 ± 50.7 s, respectively. CONCLUSION: Robot-assisted laparoscopic retroperitoneal donor nephrectomy is a safe and efficient technique that offers advantages of shorter operation time and no abdominal organ interference.
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Transplante de Rim , Laparoscopia , Robótica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Nefrectomia/métodos , Laparoscopia/métodos , Doadores VivosRESUMO
Background: Pancreatic adenocarcinoma carries a grim prognosis, and there are few recognized effective second-line treatment strategies. We attempted to evaluate the efficacy and safety of a combination of S-1, sintilimab, and anlotinib as a second-line treatment in pancreatic cancer patients with liver metastasis. Methods: Pancreatic cancer patients with liver metastases were recruited. S-1 was administered orally at 25 mg/m2 bid, anlotinib was administered orally at 12 mg qd from day 1 to day 14, and sintilimab was administered intravenously at 200 mg on day 1. This method was repeated every 21 days, and the therapeutic effect was evaluated every 3 cycles. The primary outcome was the objective response rate (ORR). Results: Overall, 23 patients were enrolled in this study of whom 19 patients had objective efficacy evaluation. The ORR was 10.5% (95% CI 0.4%-25.7%) in the evaluable population. The progression-free survival (PFS) was 3.53 (95% CI 2.50-7.50) months, and the overall survival (mOS) was 8.53 (95% CI 4.97-14.20) months. Grade 3 adverse events were 26.1%, and no grade 4 or above adverse events occurred. High-throughput sequencing was performed on the tumor tissues of 16 patients; patients with HRD-H (n = 10) had shorter PFS than those with HRD-L (n = 6) (2.43 vs. 5.45 months; P = 0.043), but there was no significant difference in OS between the two groups (4.43 vs. 9.35 months; P = 0.11). Conclusions: This study suggests the advantage of S-1 combined with sintilimab and anlotinib in extending OS as a second-line therapy in pancreatic cancer patients with liver metastasis. Clinical Trial Registration: ChiCTR2000030659.
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Adenocarcinoma , Anticorpos Monoclonais Humanizados , Indóis , Neoplasias Hepáticas , Neoplasias Pancreáticas , Quinolinas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
The RNA interference pathway mediated by microRNAs (miRNAs) is one of the methods to defend against viruses in insects. Recent studies showed that miRNAs participate in viral infection by binding to target genes to regulate their expression. Here, we found that the Bombyx mori miRNA, miR-6498-5p was down-regulated, whereas its predicted target gene pyridoxal phosphate phosphatase PHOSPHO2 (BmPLPP2) was up-regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Both in vivo and in vitro experiments showed that miR-6498-5p targets BmPLPP2 and suppresses its expression. Furthermore, we found miR-6498-5p inhibits BmNPV genomic DNA (gDNA) replication, whereas BmPLPP2 promotes BmNPV gDNA replication. As a pyridoxal phosphate (PLP) phosphatase (PLPP), the overexpression of BmPLPP2 results in a reduction of PLP content, whereas the knockdown of BmPLPP2 leads to an increase in PLP content. In addition, exogenous PLP suppresses the replication of BmNPV gDNA; in contrast, the PLP inhibitor 4-deoxypyridoxine facilitates BmNPV gDNA replication. Taken together, we concluded that miR-6498-5p has a potential anti-BmNPV role by down-regulating BmPLPP2 to modulate PLP content, but BmNPV induces miR-6498-5p down-regulation to promote its proliferation. Our findings provide valuable insights into the role of host miRNA in B. mori-BmNPV interaction. Furthermore, the identification of the antiviral molecule PLP offers a novel perspective on strategies for preventing and managing viral infection in sericulture.
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Bombyx , MicroRNAs , Nucleopoliedrovírus , Animais , Bombyx/virologia , Bombyx/genética , Bombyx/metabolismo , Regulação para Baixo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Larva/metabolismo , Larva/virologia , Larva/genética , Larva/crescimento & desenvolvimento , MicroRNAs/metabolismo , MicroRNAs/genética , Nucleopoliedrovírus/fisiologia , Fosfato de Piridoxal/metabolismo , Replicação ViralRESUMO
MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal roles in the host response to invading pathogens. Among these pathogens, Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the main causes of substantial economic losses in sericulture, and there are relatively few studies on the specific functions of miRNAs in the B. mori-BmNPV interaction. Therefore, we conducted transcriptome sequencing to identify differentially expressed (DE) messenger RNAs (mRNAs) and miRNAs in the midgut of 2 B. mori strains (BmNPV-susceptible strain P50 and BmNPV-resistant strain A35) after BmNPV infection. Through correlation analysis of the miRNA and mRNA data, we identified a comprehensive set of 21 miRNAs and 37 predicted target mRNAs. Notably, miR-3351, which has high expression in A35, exhibited remarkable efficacy in suppressing BmNPV proliferation. Additionally, we confirmed that miR-3351 binds to the 3' untranslated region (3' UTR) of B. mori glutathione S-transferase epsilon 6 (BmGSTe6), resulting in its downregulation. Conversely, BmGSTe6 displayed an opposite expression pattern to miR-3351, effectively promoting BmNPV proliferation. Notably, BmGSTe6 levels were positively correlated with glutathione S-transferase activity, consequently influencing intracellular glutathione content in the infected samples. Furthermore, our investigation revealed the protective role of glutathione against BmNPV infection in BmN cells. In summary, miR-3351 modulates glutathione content by downregulating BmGSTe6 to inhibit BmNPV proliferation in B. mori. Our findings enriched the research on the role of B. mori miRNAs in the defense against BmNPV infection, and suggests that the antiviral molecule, glutathione, offers a novel perspective on preventing viral infection in sericulture.
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Polymer infiltrated nanoporous gold is prepared by infiltrating polymer melts into a bicontinuous, nanoporous gold (NPG) scaffold. Polystyrene (PS) films with molecular weights (Mw) from 424 to 1133 kDa are infiltrated into a NPG scaffold (â¼120 nm), with a pore radius (Rp) and pore volume fraction of 37.5 nm and 50%, respectively. The confinement ratios (Γ=RgRp) range from 0.47 to 0.77, suggesting that the polymers inside the pores are moderately confined. The time for PS to achieve 80% infiltration (τ80%) is determined using in situ spectroscopic ellipsometry at 150 °C. The kinetics of infiltration scales weaker with Mw, τ80%âMw1.30±0.20, than expected from bulk viscosity Mw3.4. Furthermore, the effective viscosity of the PS melt inside NPG, inferred from the Lucas-Washburn model, is reduced by more than one order of magnitude compared to the bulk. Molecular dynamics simulation results are in good agreement with experiments predicting scaling as Mw1.4. The reduced dependence of Mw and the enhanced kinetics of infiltration are attributed to a reduction in chain entanglement density during infiltration and a reduction in polymer-wall friction with increasing polymer molecular weight. Compared to the traditional approach involving adding discrete particles into the polymer matrix, these studies show that nanocomposites with higher loading can be readily prepared, and that kinetics of infiltration are faster due to polymer confinement inside pores. These films have potential as actuators when filled with stimuli-responsive polymers as well as polymer electrolyte and fuel cell membranes.
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OBJECTS: We aim to explore the correlation between active/chronic tubulointerstitial injury and renal survival, and to compare their predictive value in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). METHOD: A total of 225 patients with MPO-AAGN diagnosed between February 2004 and December 2020 were included. Survival and univariate/multivariate Cox regression analyses were used to analyze the prognostic value of interstitial inflammation and interstitial fibrosis/tubular atrophy (IF/TA). RESULTS: Of the 225 patients, 73 (32.4%) patients developed end-stage renal disease (ESRD) requiring maintenance dialysis. Interstitial inflammation>50% and IF/TA>50% were important predictors for ESRD in MPO-AAGN in multivariate Cox regression analysis adjusted by age, gender, estimated glomerular filtration rate (eGFR)≤15 ml/min/1.73m2, and normal glomeruli% (classified by <25%, 25-50%, >50%). Furthermore, we conducted stratified Cox regression analysis and found different results in the subgroups of eGFR>15 ml/min/1.73m2 and eGFR≤15 ml/min/1.73m2. Interstitial inflammation>50% and IF/TA>50% were significant risk factors for ESRD in the subgroup of eGFR>15 ml/min/1.73m2, but not or less significant in the subgroup of eGFR≤15 ml/min/1.73m2. Similarly, the survival analysis according to interstitial inflammation>50%/≤50% and IF/TA>50%/≤50% showed significant differences in the subgroup of eGFR>15 ml/min/1.73m2, but not or less significant in the subgroup of eGFR≤15 ml/min/1.73m2. CONCLUSIONS: Interstitial inflammation>50% and IF/TA>50% were prognostic factors for renal survival in MPO-AAGN. In particular, interstitial inflammation and IF/TA had a better predictive ability in the subgroup of eGFR>15 ml/min/1.73m2. Key Points ⢠Interstitial inflammation>50% and IF/TA>50% can help to predict renal survival in MPO-AAGN. ⢠Both interstitial inflammation and IF/TA had a better predictive ability in the subgroup of eGFR>15 ml/min/1.73m2 than those in the subgroup of eGFR≤15 ml/min/1.73m2.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Falência Renal Crônica , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Estudos Retrospectivos , Glomerulonefrite/complicações , Falência Renal Crônica/diagnóstico , Prognóstico , Peroxidase , Inflamação/complicaçõesRESUMO
The renin-angiotensin system (RAS) and hypoxia have a complex interaction: RAS is activated under hypoxia and activated RAS aggravates hypoxia in reverse. Renin is an aspartyl protease that catalyzes the first step of RAS and tightly regulates RAS activation. Here, we outline kidney renin expression and release under hypoxia and discuss the putative mechanisms involved. It is important that renin generally increases in response to acute hypoxemic hypoxia and intermittent hypoxemic hypoxia, but not under chronic hypoxemic hypoxia. The increase in renin activity can also be observed in anemic hypoxia and carbon monoxide-induced histotoxic hypoxia. The increased renin is contributed to by juxtaglomerular cells and the recruitment of renin lineage cells. Potential mechanisms regulating hypoxic renin expression involve hypoxia-inducible factor signaling, natriuretic peptides, nitric oxide, and Notch signaling-induced renin transcription.
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With the widespread adoption of ultrasound guidance, Seldinger puncture techniques, and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years, an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices (TIVADs) in the upper arm. This approach has the advantage of completely avoiding the risks of hemothorax, pneumothorax, and neck and chest scarring. Medical specialties presently engaged in this study in China include internal medicine, surgery, anesthesiology, and interventional departments. However, command over implantation techniques, treatment of complications, and proper use and maintenance of TIVAD remain uneven among different medical units. Moreover, currently, there are no established quality control standards for implantation techniques or specifications for handling complications. Thus, this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach, reduce complication rates, and ensure patient safety. This consensus elaborates on the technical indications and contraindications, procedures and technical points, treatment of complications, and the use and maintenance of upper-arm TIVAD, thus providing a practical reference for medical staff.
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This is a phase II study of PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC, respectively). Twenty-nine patients are enrolled in the study. The objective response rate (ORR) is 60%, and the R0 resection rate is 90% (9/10). The 12-month progression-free survival (PFS) rate and 12-month overall survival (OS) rate are 64% and 72%, respectively. Grade 3 or higher adverse events are anemia (8%), thrombocytopenia (8%), and jaundice (8%). Circulating tumor DNA analysis reveals that patients with a >50% decline in maximal somatic variant allelic frequency (maxVAF) between the first clinical evaluation and baseline have a longer survival outcome and a higher response rate and surgical rate than those who are not. PD-1 blockade plus chemoradiotherapy as preoperative therapy displays promising antitumor activity, and multiomics potential predictive biomarkers are identified and warrant further verification.
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Neoplasias Pancreáticas , Receptor de Morte Celular Programada 1 , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/tratamento farmacológico , Terapia Neoadjuvante , Quimiorradioterapia , Intervalo Livre de ProgressãoRESUMO
OBJECTIVES: This study aims to compare the prognostic values of two histopathological classification, Berden's classification versus renal risk score (RRS) by Brix et al. for predicting renal survival in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (MPO-AAGN). METHODS: The medical records of 225 patients with MPO-AAGN diagnosed in our centre between February 2004 and December 2020 were retrospectively analysed. The predictive model of Berden's classification or RRS was established by Cox regression, respectively. The above two models were compared on aspects of discrimination, calibration, and decision curve analysis for predicting the 0.5-, 1-, 3-, and 5-year renal survival. RESULTS: After a median follow up of 38.99 months, 32.44% of patients developed end-stage renal disease (ESRD). In the Kaplan-Meier analysis, there were significant differences in renal survival among groups according to Berden's classification or RRS (both log-rank p<0.001). According to time-dependent receiver operating characteristic (ROC) curve analysis, the model based on RRS showed better discrimination ability than the model based on Berden's classification for predicting 0.5-, 1-, and 3-year renal survival. For calibration analysis, the model based on RRS showed worse calibration than the model based on Berden's classification for predicting 1- and 3-year renal survival. According to the decision curve analysis, the clinical decisions based on RRS could achieve more clinical benefits than those based on Berden's classification in predicting 0.5-, 1-, and 3-year renal survival. CONCLUSIONS: The model based on RRS has better predictive value for renal survival than Berden's classification in aspect of discrimination and clinical decision from 0.5- to 3-year renal survival.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Falência Renal Crônica , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Estudos Retrospectivos , Peroxidase , População do Leste Asiático , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Fatores de RiscoRESUMO
Immune checkpoint inhibitors have limited efficacy in metastatic pancreatic cancer due to the complex tumor immune microenvironment (TIME). Studies have shown that radiotherapy can cause cell lesions to release tumor antigens and then take part in the remodeling of the tumor environment and the induction of ectopic effects via regional and systemic immunoregulation. Here, we reported a case of advanced metastatic pancreatic cancer treated with immunotherapy combined with chemotherapy and radiotherapy and a sharp shift of the TIME from T3 to T2 was also observed. One hepatic metastasis within the planning target volume (PTV) was evaluated complete response (CR), the other one was evaluated partial response (PR) and 2 hepatic metastases outside the PTV were surprisingly considered PR. In the study, we found that immunotherapy combined with chemotherapy and radiotherapy achieved significant therapeutic benefits, which may provide a new strategy for the treatment of advanced pancreatic cancer.
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Imunoterapia , Neoplasias Pancreáticas , Humanos , Antígenos de Neoplasias , Microambiente TumoralRESUMO
The emergence of multimodal medical imaging technology greatly increases the accuracy of clinical diagnosis and etiological analysis. Nevertheless, each medical imaging modal unavoidably has its own limitations, so the fusion of multimodal medical images may become an effective solution. In this paper, a novel fusion method on the multimodal medical images exploiting convolutional neural network (CNN) and extreme learning machine (ELM) is proposed. As a typical representative in deep learning, CNN has been gaining more and more popularity in the field of image processing. However, CNN often suffers from several drawbacks, such as high computational costs and intensive human interventions. To this end, the model of convolutional extreme learning machine (CELM) is constructed by incorporating ELM into the traditional CNN model. CELM serves as an important tool to extract and capture the features of the source images from a variety of different angles. The final fused image can be obtained by integrating the significant features together. Experimental results indicate that, the proposed method is not only helpful to enhance the accuracy of the lesion detection and localization, but also superior to the current state-of-the-art ones in terms of both subjective visual performance and objective criteria.
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Aim: We aimed to evaluate the efficacy and safety of individualized chemotherapy combined with sequential immunotherapy based on BRCA1 mRNA expression in unresectable pancreatic cancer. Methods: The expression of BRCA1 mRNA in tumor tissues of 25 patients with pancreatic cancer was detected in this retrospective study. Patients in the medium and high expression groups were treated with paclitaxel-based chemotherapy: albumin paclitaxel 125mg/m2, gemcitabine 1g/m2, day 1. Patients in the low expression group were treated with oxaliplatin-based chemotherapy: oxaliplatin 85mg/m2, gemcitabine 1g/m2, day 1. Sequential GM-CSF and IL-2 immunotherapy were applied. Patient condition, treatment efficacy and safety were assessed every 4 cycles. Results: A total of 25 patients were enrolled in the study. All of them were observed for toxic side effects and 24 of them were evaluated for efficacy. The median overall survival and median progression-free survival were 11.9 months and 6.3 months. The disease control rate was 91.7%, of which 37.5% (9/24) patients achieved partial remission (PR), 54.2% (13/24) patients achieved stable disease (SD) and 8.3% (2/24) patients were assessed as progressive disease(PD). Of the 15 patients with medium or high expression in BRCA1 mRNA, 7 achieved PR and 8 achieved SD. Of the 9 patients with low BRCA1 mRNA expression, 2 achieved PR, 5 achieved SD and 2 had PD. The proportion of eosinophils in the blood of some patients with good therapeutic effects was significantly higher than that before treatment. Hematological and non-hematological toxicity during the treatment were mostly grade 1~2. The two most common grade 3 to 4 adverse events were fever and thrombocytopenia. Conclusion: Our results suggest that individualized selection of chemotherapy combined with sequential immunotherapy according to BRCA1 mRNA expression level in unresectable pancreatic cancer could control the disease and have controllable adverse reactions.
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Previous clinical studies had not shown expected results in advanced pancreatic cancer (APC) with single-agent checkpoint inhibitors. Until the present day, little is known about their performance in real-world settings. So, in this study, we investigate the ICIs' efficacy and safety in Chinese APC patients. Patients with APC who received ICIs between November 2018 to June 2021 were enrolled in this retrospective study. The efficacy end points included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). This study included 104 patients and the median OS (mOS) and median PFS (mPFS) were 9.1 and 5.4 months, respectively. In the subgroup analyses, the mOS was longer for patients receiving combined radiotherapy than for those that didn't (13.8 vs 7.0 months, p < .001), whereas the mPFS was also longer, and the ORR and DCR were higher. Specifically, the mOS was longer for patients who had received a combination of chemotherapy than for those combined with targeted therapy (11.6 vs 5.6 months, p = .002), with the mPFS being also longer. ICIs as a first-line treatment could resulted to better survival. The mOS was longer for patients with a high TMB compared to those with low (19.3 vs 7.2 months, p = .004), whereas AEs were considered to be tolerable. The combination therapy of ICIs was proved to be safe and effective for treating APC, especially the combination of chemotherapy and radiotherapy, which would benefit from additional prospective studies.
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Inibidores de Checkpoint Imunológico , Neoplasias Pancreáticas , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Prospectivos , População do Leste Asiático , Estudos Retrospectivos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias PancreáticasRESUMO
Carbon monoxide (CO) poisoning causes myocardial injury, which is attenuated by hyperbaric oxygen therapy (HBOT). During CO poisoning, the body increases anti-inflammatory proteins, including heme oxygenase-1 (HO-1), in response to oxidative stress. Considering the myocardial injury resulting from CO poisoning and the lack of sufficient information about the effect of HBOT on HO-1, the present study evaluated the effect of hyperbaric oxygen therapy on heme oxygenase-1 (HO-1) in patients with acute carbon monoxide poisoning and myocardial injury. In this regard, in a before-after Quasi-Experimental study, 20 patients with carbon monoxide poisoning and myocardial injury were studied. All patients underwent 40 daily hyperbaric oxygen therapy sessions for 90 minutes at a pressure of 2.4 ATA. Also, 20 healthy individuals, as a control group, were participated. To evaluate and compare the mRNA level of the HO-1 gene, the Real-time PCR technique was used. Paired t-test was used to compare the two indices of 6min walking distance and pulmonary arterial pressure (PAP) before and after the intervention. The results showed that the difference during 12 weeks was 8.65 ± 4.91 for PAP, and this reduction in pressure was statistically significant (P = 0.0092). The distance traveled increased by 28 ± 10.88 m in 6 minutes at the end of the study (P = 0.0084). Regarding the expression level of HO-1, the results showed that the expression level in the intervention group before the test had a significant increase compared to the control group (p = 0.0004). However, after hyperbaric oxygen therapy, the expression of this gene decreased significantly, and there was no statistically significant difference with the control group (p = 0.062). Overall, the results showed that HBOT significantly decreased HO-1 gene expression in CO poisoning and myocardial injury patients. It indicates the importance of HBOT in the treatment and compensation of cardiac tissue damage caused by CO poisoning.
Assuntos
Intoxicação por Monóxido de Carbono , Oxigenoterapia Hiperbárica , Monóxido de Carbono , Intoxicação por Monóxido de Carbono/terapia , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , RNA Mensageiro/genéticaRESUMO
Background: Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with a low resection rate. Chemotherapy and radiotherapy (RT) are the main treatment approaches for patients with advanced pancreatic cancer, and neoadjuvant chemoradiotherapy is considered a promising strategy to increase the resection rate. Recently, immune checkpoint inhibitor (ICI) therapy has shown remarkable efficacy in several cancers. Therefore, the combination of ICI, chemotherapy, and concurrent radiotherapy is promising for patients with potentially resectable pancreatic cancer, mainly referring to locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC), to increase the chances of conversion to surgical resectability and prolong survival. This study aims to introduce the design of a clinical trial. Methods: This is an open-label, single-arm, and single-center phase II trial. Patients with pathologically and radiographically confirmed LAPC or BRPC without prior anti-cancer treatment or severe morbidities will be enrolled. All patients will receive induction therapy and will be further evaluated by the Multiple Disciplinary Team (MDT) for the possibility of surgery. The induction therapy consists of up to four cycles of gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 via intravenous (IV) infusion on days 1 and 8, along with tislelizumab (a PD-1 monoclonal antibody) 200 mg administered through IV infusion on day 1 every 3 weeks, concurrently with stereotactic body radiation therapy (SBRT) during the third cycle of treatment. After surgery, patients without progression will receive another two to four cycles of adjuvant therapy with gemcitabine, nab-paclitaxel, and tislelizumab. The primary objectives are objective response rate (ORR) and the R0 resection rate. The secondary objectives are median overall survival (mOS), median progression free survival (mPFS), disease control rate (DCR), pathological grade of tumor tissue after therapy, and adverse reactions. Besides, we expect to explore the value of circulating tumor DNA (ctDNA) in predicting tumor response to induction therapy and survival outcome of patients. Discussion: This is a protocol for a clinical trial that attempts to evaluate the safety and efficacy of the combination of anti-PD-1 antibody plus chemotherapy and radiotherapy as the induction therapy for LAPC and BRPC. The results of this phase II study will provide evidence for the clinical practice of this modality. Clinical Trial Registration: http://www.chictr.org.cn/edit.aspx?pid=53720&htm=4, identifier ChiCTR2000032955.