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1.
Molecules ; 29(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38731653

RESUMO

In pursuit of enhancing the mechanical properties, especially the tensile strength, of 4D-printable consumables derived from waste cooking oil (WCO), we initiated the production of acrylate-modified WCO, which encompasses epoxy waste oil methacrylate (EWOMA) and epoxy waste oil acrylate (EWOA). Subsequently, a series of WCO-based 4D-printable photocurable resins were obtained by introducing a suitable diacrylate molecule as the second monomer, coupled with a composite photoinitiator system comprising Irgacure 819 and p-dimethylaminobenzaldehyde (DMAB). These materials were amenable to molding using an LCD light-curing 3D printer. Our findings underscored the pivotal role of triethylene glycol dimethacrylate (TEGDMA) among the array of diacrylate molecules in enhancing the mechanical properties of WCO-based 4D-printable resins. Notably, the 4D-printable material, composed of EWOA and TEGDMA in an equal mass ratio, exhibited nice mechanical strength comparable to that of mainstream petroleum-based 4D-printable materials, boasting a tensile strength of 9.17 MPa and an elongation at break of 15.39%. These figures significantly outperformed the mechanical characteristics of pure EWOA or TEGDMA resins. Furthermore, the EWOA-TEGDMA resin demonstrated impressive thermally induced shape memory performance, enabling deformation and recovery at room temperature and retaining its shape at -60 °C. This resin also demonstrated favorable biodegradability, with an 8.34% weight loss after 45 days of soil degradation. As a result, this 4D-printable photocurable resin derived from WCO holds immense potential for the creation of a wide spectrum of high-performance intelligent devices, brackets, mold, folding structures, and personalized products.

2.
Int J Biol Sci ; 20(7): 2640-2657, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725843

RESUMO

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteína HMGA1a , Inibidores de MTOR , Proteína Proto-Oncogênica c-ets-1 , Humanos , Linhagem Celular Tumoral , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteína Proto-Oncogênica c-ets-1/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Proteína HMGA1a/metabolismo , Proteína HMGA1a/genética , Inibidores de MTOR/farmacologia , Inibidores de MTOR/uso terapêutico , Proteína 1A de Ligação a Tacrolimo/metabolismo , Proteína 1A de Ligação a Tacrolimo/genética , Animais , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Camundongos Nus
3.
Nat Med ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740994

RESUMO

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

4.
World J Clin Cases ; 12(14): 2350-2358, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38765753

RESUMO

BACKGROUND: This study presents an evaluation of the computed tomography lymphangiography (CTL) features of lymphatic plastic bronchitis (PB) and primary chylothorax to improve the diagnostic accuracy for these two diseases. AIM: To improve the diagnosis of lymphatic PB or primary chylothorax, a retrospective analysis of the clinical features and CTL characteristics of 71 patients diagnosed with lymphatic PB or primary chylothorax was performed. METHODS: The clinical and CTL data of 71 patients (20 with lymphatic PB, 41 with primary chylothorax, and 10 with lymphatic PB with primary chylothorax) were collected retrospectively. CTL was performed in all patients. The clinical manifestations, CTL findings, and conventional chest CT findings of the three groups of patients were compared. The chi-square test or Fisher's exact test was used to compare the differences among the three groups. A difference was considered to be statistically significant when P < 0.05. RESULTS: (1) The percentages of abnormal contrast medium deposits on CTL in the three groups were as follows: Thoracic duct outlet in 14 (70.0%), 33 (80.5%) and 8 (80.0%) patients; peritracheal region in 18 (90.0%), 15 (36.6%) and 8 (80.0%) patients; pleura in 6 (30.0%), 33 (80.5%) and 9 (90.0%) patients; pericardium in 6 (30.0%), 6 (14.6%) and 4 (40.0%) patients; and hilum in 16 (80.0%), 11 (26.8%) and 7 (70.0%) patients; and (2) the abnormalities on conventional chest CT in the three groups were as follows: Ground-glass opacity in 19 (95.0%), 18 (43.9%) and 8 (80.0%) patients; atelectasis in 4 (20.0%), 26 (63.4%) and 7 (70.0%) patients; interlobular septal thickening in 12 (60.0%), 11 (26.8%) and 3 (30.0%) patients; bronchovascular bundle thickening in 14 (70.0%), 6 (14.6%) and 4 (40.0%) patients; localized mediastinal changes in 14 (70.0%), 14 (34.1%), and 7 (70.0%) patients; diffuse mediastinal changes in 6 (30.0%), 5 (12.2%), and 3 (30.0%) patients; cystic lesions in the axilla in 2 (10.0%), 6 (14.6%), and 2 (20.0%) patients; and cystic lesions in the chest wall in 0 (0%), 2 (4.9%), and 2 (4.9%) patients. CONCLUSION: CTL is well suited to clarify the characteristics of lymphatic PB and primary chylothorax. This method is an excellent tool for diagnosing these two diseases.

5.
Int J Sports Med ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698624

RESUMO

Hydrogen, as an antioxidant, may have the potential to mitigate fatigue and improve selected oxidative stress markers induced by strenuous exercise. This study focused on previously unexplored approach of pre-exercise inhalation of hydrogen-rich gas (HRG). Twenty-four healthy adult men first completed prelaboratories to determine maximum cycling power (Wmax) and maximum cycling time (Tmax). Then they were subjected to ride Tmax at 80% Wmax on cycle ergometers after inhaled HRG or placebo gas (air) for 60-minute in a double-blind, counterbalanced, randomized, and crossover design. The cycling frequency in the fatigue modelling process and the rating of perceived exertion (RPE) at the beginning and end of the ride were recorded. Before gas inhalation and after fatigue modeling, visual analog scale (VAS) for fatigue and counter-movement jump (CMJ) were tested, and blood samples were obtained. The results showed that compared to placebo, HRG inhalation induced significant improvement in VAS, RPE, the cycling frequency in the last 30 seconds, the ability to inhibit hydroxyl radicals, and serum lactate after exercise (p < 0.028), but not in CMJ height and glutathione peroxidase activit. In conclusions, HRG inhalation prior to acute exercise can alleviate exercise-induced fatigue, maintain functional performance, and improve hydroxyl radical and lactate levels.

6.
AME Case Rep ; 8: 48, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711902

RESUMO

Background: Non-small cell lung cancer (NSCLC) has a high incidence of lung cancer, with a 30% incidence of KRAS mutations and a low 5-year survival rate. Until the Food and Drug Administration (FDA) approved sotorasib in May 2021, no therapies targeted mutated KRAS in cancer. Sotorasib, a new KRAS inhibitor, is currently recognized as the newest clinically targeted agent with apparent clinical efficacy in NSCLC patients with KRAS G12C mutations. FDA approval is required for patients with advanced or metastatic NSCLC undergoing at least one chemotherapy regimen. Case Description: In our study, we report a patient with advanced NSCLC combined with brain metastases, clinical stage IV (c.T3N0M1b), KRAS G12C (+) detected by next-generation sequencing (NGS) technology, direct use of sotorasib, an inhibitor of KRAS G12C, as first-line therapy. The patient was treated with 4 months of oral therapy, had significant partial remission (PR), and remained in stable disease (SD) for nearly 9 months of follow-up, with no other side effects. Further extension of the follow-up period is needed to assess the impact of sotorasib as first-line therapy on patient survival. A series of clinical trials in phase 3 is ongoing, covering the first-line usage widespread. Conclusions: Based on the literature review, this is the first domestic report in China where sotorasib was used directly as first-line treatment in patients with advanced combined brain metastasis from NSCLC. It needs a longer follow-up to evaluate the efficacy of sotorasib further as a first-line.

7.
Front Immunol ; 15: 1390082, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756782

RESUMO

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics. This study reports on a case of ceftizoxime-induced hemolysis observed in a patient in China. Case description: A Chinese patient diagnosed with malignant rectal cancer underwent antimicrobial therapy after laparoscopic partial recto-sigmoid resection (L-Dixon). After receiving four doses of ceftizoxime, the patient developed symptoms including rash, itchy skin, and chest distress, followed by a rapid decline in hemoglobin levels, the presence of hemoglobin in the urine (hemoglobinuria), renal failure, and disseminated intravascular coagulation. Laboratory analysis revealed high-titer antibodies against ceftizoxime and red blood cells (RBCs) in the patient's serum, including immunoglobulin M (IgM) (1:128) antibodies and immunoglobulin G (IgG) (1:8) antibodies, with noted crossreactivity to ceftriaxone. Significant improvement in the patient's hemolytic symptoms was observed following immediate discontinuation of the drug, two plasma exchanges, and extensive RBC transfusion. Conclusion: This case, together with previous reports, underscores the importance of considering DIIHA in patients who exhibit unexplained decreases in hemoglobin levels following antibiotic therapy. A thorough examination of the patient's medical history can provide crucial insights for diagnosing DIIHA. The effective management of DIIHA includes immediate cessation of the implicated drug, plasma exchange, and transfusion support based on the identification of specific drug-dependent antibodies through serological testing.


Assuntos
Antibacterianos , Ceftizoxima , Hemoglobinas , Insuficiência de Múltiplos Órgãos , Neoplasias Retais , Humanos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/imunologia , Neoplasias Retais/cirurgia , Hemoglobinas/metabolismo , Antibacterianos/efeitos adversos , Masculino , Ceftizoxima/efeitos adversos , Insuficiência de Múltiplos Órgãos/etiologia , Pessoa de Meia-Idade , Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/imunologia , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etiologia , Anemia Hemolítica Autoimune/induzido quimicamente , Anemia Hemolítica Autoimune/imunologia , Anemia Hemolítica Autoimune/diagnóstico , China , População do Leste Asiático
8.
J Hepatol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38759889

RESUMO

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme OXCT1. We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in hepatocellular carcinoma in vivo, we conducted multiplex immunohistochemistry (mIHC) experiments on human HCC specimens. To explore the role of OXCT1 in mouse hepatocellular carcinoma tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4 trimethylation (H3K4me3) level in the Arg1 promoter. In addition, Pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreasing CD8+ T-cell exhaustion and deceleration of tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in HCC patients. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping HCC progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for HCC. Here, we found that ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. And the strategic pharmacological intervention or genetic downregulation of OXCT1 in TAMs enhances the antitumor immunity and decelerated tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer.

9.
Cell Death Differ ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719928

RESUMO

Neuronal ferroptosis plays a key role in neurologic deficits post intracerebral hemorrhage (ICH). However, the endogenous regulation of rescuing ferroptotic neurons is largely unexplored. Here, we analyzed the integrated alteration of metabolomic landscape after ICH using LC-MS and MALDI-TOF/TOF MS, and demonstrated that aconitate decarboxylase 1 (Irg1) and its product itaconate, a derivative of the tricarboxylic acid cycle, were protectively upregulated. Deficiency of Irg1 or depletion of neuronal Irg1 in striatal neurons was shown to exaggerate neuronal loss and behavioral dysfunction in an ICH mouse model using transgenic mice. Administration of 4-Octyl itaconate (4-OI), a cell-permeable itaconate derivative, and neuronal Irg1 overexpression protected neurons in vivo. In addition, itaconate inhibited ferroptosis in cortical neurons derived from mouse and human induced pluripotent stem cells in vitro. Mechanistically, we demonstrated that itaconate alkylated glutathione peroxidase 4 (GPx4) on its cysteine 66 and the modification allosterically enhanced GPx4's enzymatic activity by using a bioorthogonal probe, itaconate-alkyne (ITalk), and a GPx4 activity assay using phosphatidylcholine hydroperoxide. Altogether, our research suggested that Irg1/itaconate-GPx4 axis may be a future therapeutic strategy for protecting neurons from ferroptosis post ICH.

10.
Heliyon ; 10(7): e27362, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560168

RESUMO

Background: Primary liver cancer (PLC) is a prevalent malignancy of the digestive system characterized by insidious symptom onset and a generally poor prognosis. Recent studies have highlighted a significant correlation between the initiation and prognosis of liver cancer and the immune function of PLC patients. Purpose: Revealing the expression of PLC-related immune genes and the characteristics of immune cell infiltration provides assistance for the analysis of clinical pathological parameters and prognosis of PLC patients. Methods: PLC-related differentially expressed genes (DEGs) with a median absolute deviation (MAD > 0.5) were identified from TCGA and GEO databases. These DEGs were intersected with immune-related genes (IRGs) from the ImmPort database to obtain PLC-related IRGs. The method of constructing a prognostic model through immune-related gene pairs (IRGPs) is used to obtain IRGPs and conduct the selection of central immune genes. The central immune genes obtained from the selection of IRGPs are validated in PLC. Subsequently, the relative proportions of 22 types of immune cells in different immune risk groups are evaluated, and the differential characteristics of PLC-related immune cells are verified through animal experiments. Results: Through database screening and the construction of an IRGP prognosis model, 84 pairs of IRGPs (P < 0.001) were ultimately obtained. Analysis of these 84 IRGPs revealed 11 central immune genes related to PLC, showing differential expression in liver cancer tissues compared to normal liver tissues. Results from the CiberSort platform indicate differential expression of immune cells such as naive B cells, macrophages, and neutrophils in different immune risk groups. Animal experiments demonstrated altered immune cell proportions in H22 tumor-bearing mice, validating findings from peripheral blood and spleen homogenate analyses. Conclusion: Our study successfully predicted and validated PLC-related IRGs and immune cells, suggesting their potential as prognostic indicators and therapeutic targets for PLC.

11.
Eur Neurol ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565087

RESUMO

INTRODUCTION: Malignant cerebral edema (MCE) is a serious complication and the main cause of poor prognosis in patients with large-hemisphere infarction (LHI). Therefore, the rapid and accurate identification of potential patients with MCE is essential for timely therapy. This study utilized an artificial intelligence-based machine learning approach to establish an interpretable model for predicting MCE in patients with LHI. METHODS: This study included 314 patients with LHI not undergoing recanalization therapy. The patients were divided into MCE and non-MCE groups, the extreme Gradient boosting (XGBoost) model was developed. A confusion matrix was used to measure the prediction performance of the XGBoost model. We also utilized the SHapley Additive extension (SHAP) method to explain the XGBoost model. Decision curve analysis and receiver operating characteristic (ROC) curve were performed to evaluate the net benefits of the model. RESULTS: MCE was observed in 121(38.5%) of the 314 patients with LHI. The model showed excellent predictive performance, with an area under the curve of 0.916. The SHAP method revealed the top 10 predictive variables of the MCE such as ASPECTS score, NIHSS score, CS score, APACHE II score, HbA1c, AF, NLR, PLT, GCS and Age based on their importance ranking. CONCLUSION: An interpretable predictive model can increase transparency and help doctors accurately predict the occurrence of MCE in LHI patients, not undergoing recanalization therapy within 48h from onset, providing patients with better treatment strategies and enabling optimal resource allocation.

12.
Skin Res Technol ; 30(4): e13652, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572582

RESUMO

OBJECTIVE: To investigate whether compression therapy after thermal ablation of varicose veins can improve the prognosis of patients. METHODS: Systematic research were applied for Chinese and English electronic databases(PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, VIP Databases). Eligible prospective studies that comparing the efficacy of compression therapy and non-compression therapy on patients after thermal ablation of varicose veins were included. The interest outcome such as pain, quality of life (QOL), venous clinical severity score (VCSS), time to return to work and complications were analyzed. RESULTS: 10 studies were of high quality, and randomized controlled trials involving 1,545 patients met the inclusion criteria for this study. At the same time, the meta-analysis showed that the application of compression therapy improved pain (SMD: -0.51, 95% CI: -0.95, -0.07) but exhibited no statistically significant effect on QOL (SMD: 0.04, 95% CI: -0.08, 0.16), VCSS (MD: -0.05, 95% CI: -1.19, 1.09), time to return to work (MD: -0.43, 95% CI: -0.90, 0.03), total complications (RR: 0.54, 95% CI: 0.27, 1.09), and thrombosis (RR: 0.71, 95% CI: 0.31, 1.62). CONCLUSION: Compression therapy after thermal ablation of varicose veins can slightly relieve pain, but it has not been found to be associated with improvement in other outcomes.


Assuntos
Ablação por Cateter , Terapia a Laser , Varizes , Humanos , Qualidade de Vida , Estudos Prospectivos , Terapia a Laser/métodos , Varizes/cirurgia , Varizes/etiologia , Dor/etiologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
J Cyst Fibros ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38580563

RESUMO

BACKGROUND: Ivacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety, pharmacokinetics (PK), and efficacy of IVA in a small cohort of infants aged 1 to <4 months with CF. METHODS: In this phase 3, open-label study, infants 1 to <4 months with CF and an IVA-responsive CFTR variant received an initial low dose of IVA based on age and weight. Because IVA is a sensitive CYP3A substrate and CYP3A maturation is uncertain in infants, doses were adjusted at day 15 to better match median adult exposures based on individual PK measurements taken on day 4. Primary endpoints were safety and PK measurements. RESULTS: Seven infants (residual function CFTR variants [n=5]; minimal function CFTR variants [n=2]) received ≥1 dose of IVA. Six infants had doses adjusted at day 15 and one infant did not require dose adjustment; subsequent PK analyses showed mean trough concentrations for IVA and metabolites were within range of prior clinical experience. Four infants (57.1%) had adverse events (AEs); no serious AEs were noted. One infant discontinued study drug due to a non-serious AE of elevated alanine aminotransferase >8x the upper limit of normal. Mean sweat chloride concentration decreased (-40.3 mmol/L [SD: 29.2]) through week 24. Improvements in biomarkers of pancreatic function and intestinal inflammation, as well as growth parameters, were observed. CONCLUSIONS: In this small, open-label study, IVA dosing in infants achieved exposures previously shown to be safe and efficacious. Because PK was predictable, a dosing regimen based on age and weight is proposed. IVA was generally safe and well tolerated, and led to improvements in CFTR function, markers of pancreatic function and intestinal inflammation, and growth parameters, supporting use in infants as young as 1 month of age.

14.
BMC Urol ; 24(1): 82, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594657

RESUMO

OBJECTIVES: Redo surgery for pelvic fracture urethral distraction defects (PFUDDs) is still a challenge. the long urethral defect makes it difficult while the high tension increase the recurrence rate. Although certain ancillary maneuvers can relieve tension, there is no consensus or guidelines for the prediction/planning of the selection. In this study, we present our experience with developing an intraoperative guidance system to achieve tension-free urethral anastomosis. PATIENTS AND METHODS: A total of 91 recurrent PFUDD patients managed at our center between 2020 and 2022 were retrospectively analyzed. The patients underwent scar removing and urethral anastomosis. For the long defect and high-tension cases, 6 kinds of tension-relieving maneuvers were used respectively during the process of urethral anastomosis. Preoperative assessment of the urethrogram was done before surgery, while biaxial (vertical and horizontal) defect measurements were performed intraoperatively. The patients were followed-up for 12 months (8.9 ± 4.2), furthermore, recurrence and complications were analyzed. RESULTS: The overall success rate was 86.81%. The mean defect in urethrogram was 2.9 ± 1.1 cm. 27 simple anastomosis was performed when the vertical plus horizontal defect was less than 2 cm with 11.11% recurrence. 24 cavernous septum splittings were performed when the horizontal defect was greater than 2 cm with 8.33% recurrence. 21 inferior pubectomies were performed when the horizontal defect was greater than 3 cm with 19.05% recurrence. 15 ancillary distal urethra manipulations (fully distal urethral mobilization, urethral suspension and corpus cavernosa folding) were performed when the vertical defect was 3 to 4 cm with 13.33 recurrence. 4 reroutings were performed when the vertical defect was greater than 4 cm with 25.00% recurrence. CONCLUSIONS: Ancillary maneuvers are effective for reducing tension in redo urethral anastomosis. Measurement of divergent vertical and horizontal urethral defects could guide the selection of ancillary maneuvers. Combined tension-relieving maneuvers is recommended according to the defect direction and length to achieve a tension-free anastomosis.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Estreitamento Uretral , Humanos , Uretra/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Anastomose Cirúrgica/efeitos adversos , Fraturas Ósseas/complicações , Estreitamento Uretral/cirurgia , Resultado do Tratamento
15.
J Thorac Dis ; 16(3): 1765-1776, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38617761

RESUMO

Background: Accurate prediction of occult lymph node metastasis (ONM) is an important basis for determining whether lymph node (LN) dissection is necessary in clinical stage IA lung adenocarcinoma patients. The aim of this study is to determine the best machine learning algorithm for radiomics modeling and to compare the performances of the radiomics model, the clinical-radilogical model and the combined model incorporate both radiomics features and clinical-radilogical features in preoperatively predicting ONM in clinical stage IA lung adenocarcinoma patients. Methods: Patients with clinical stage IA lung adenocarcinoma undergoing curative surgery from one institution were retrospectively recruited and assigned to training and test cohorts. Radiomics features were extracted from the preoperative computed tomography (CT) images of the primary tumor. Seven machine learning algorithms were used to construct radiomics models, and the model with the best performance, evaluated using the area under the curve (AUC), was selected. Univariate and multivariate logistic regression analyses were performed on the clinical-radiological features to identify statistically significant features and to develop a clinical model. The optimal radiomics and clinical models were integrated to build a combined model, and its predictive performance was assessed using receiver operating characteristic curves, Brier score, and decision curve analysis (DCA). Results: This study included 258 patients who underwent resection (training cohort, n=182; test cohort, n=76). Six radiomics features were identified. Among the seven machine learning algorithms, extreme gradient boosting (XGB) demonstrated the highest performance for radiomics modeling, with an AUC of 0.917. The combined model improved the AUC to 0.933 and achieved a Brier score of 0.092. DCA revealed that the combined model had optimal clinical efficacy. Conclusions: The superior performance of the combined model, based on XGB algorithm in predicting ONM in patients with clinical stage IA lung adenocarcinoma, might aid surgeons in deciding whether to conduct mediastinal LN dissection and contribute to improve patients' prognosis.

16.
Huan Jing Ke Xue ; 45(5): 3016-3026, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629562

RESUMO

Sweet sorghum has a large biomass and strong cadmium (Cd) absorption capacity, which has the potential for phytoremediation of Cd-contaminated soil. In order to study the Cd phytoremediation effect of sweet sorghum assisted with citric acid on the typical parent materials in southern China, a field experiment was carried out in two typical parent material farmland areas (neutral purple mud field and jute sand mud field) with Cd pollution in Hunan Province. The results showed that:① Citric acid had no inhibitory effect on the growth of sweet sorghum. After the application of citric acid, the aboveground biomass of sweet sorghum at the maturity stage increased by 10.1%-24.7%. ② Both sweet sorghum planting and citric acid application reduced the soil pH value, and the application of citric acid further reduced the soil pH value at each growth stage of sweet sorghum; this decrease was greater in the neutral purple mud field, which decreased by 0.24-0.72 units. ③ Both sweet sorghum planting and citric acid application reduced the total amount of soil Cd, and the decreases in the neutral purple mud field and jute sand mud field were 23.8%-52.2% and 17.1%-31.8%, respectively. The acid-extractable percentage of soil Cd in both places increased by 38.6%-147.7% and 4.8%-22.7%, respectively. ④ The application of citric acid could significantly increase the Cd content in various tissues of sweet sorghum. The Cd content in the aboveground part of the plant in the neutral purple mud field was higher than that in the jute sand mud field, and the Cd content in stems and leaves was 0.25-1.90 mg·kg-1 and 0.21-0.64 mg·kg-1, respectively. ⑤ After applying citric acid, the Cd extraction amount of sweet sorghum in neutral purple mud soil in the mature stage reached 47.56 g·hm-2. In summary, citric acid could enhance the efficiency of sweet sorghum in the phytoremediation of Cd-contaminated soil, and the effect was better in neutral purple mud fields. This technology has the potential for remediation coupled with agro-production for heavy metal-contaminated farmland.


Assuntos
Poluentes do Solo , Sorghum , Cádmio/análise , Biodegradação Ambiental , Solo , Areia , Ácido Cítrico , Poluentes do Solo/análise , China , Grão Comestível/química
17.
Medicine (Baltimore) ; 103(15): e37575, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608122

RESUMO

A comprehensive understanding of physical activity levels (PAL) among Chinese pregnant women and an exploration, from a continuous care perspective, of various factors influencing these activity levels. Investigating the correlations between adverse habits, psychological factors, and PAL in prenatal health management. This study aims to provide substantial guidance for prenatal health management and personalized care, offering recommendations to healthcare professionals and policymakers to enhance the overall health and well-being of pregnant women. This study enrolled 1256 pregnant women as research subjects. Baseline information was collected through a personal information collection form. Subsequently, continuous care was provided during the early, middle, and late stages of pregnancy, documenting the respective influencing factors. Simultaneously, the International Physical Activity Questionnaire (IPAQ) was utilized to assess the PAL of pregnant women across different trimesters. Finally, using the SPSS software version 25.0, a combined approach of generalized linear mixed effects (GLME) models and multivariate logistic regression was used to statistically analyze the collected data, comprehensively exploring the influencing factors of PAL during pregnancy. The proportion of research subjects engaged in low-level physical activity decreased from 60.80% to 40.34% across various stages of pregnancy, while the proportion engaged in moderate-level physical activity ranged from 25.32% to 40.75%. Meanwhile, the proportion engaged in high-level physical activity accounted for 13.88% to 18.91%.There was P = .021 and ß = -0.276 for smoking before pregnancy. The P-value of pregnant women who smoke in the second trimester was.035, the Odds Ratio (OR) value was 0.638, and the 95% confidence interval (CI) was (0.406, 0.972). The difference was statistically significant (all P < .05). In China, the physical activity level of pregnant women is generally low, which is related to factors such as smoking, alcohol consumption, sleep disorders, and depression during pregnancy. Medical personnel should improve the living habits of pregnant women and enhance their PAL through measures such as health education and psychological counseling.


Assuntos
Consumo de Bebidas Alcoólicas , Gestantes , Gravidez , Humanos , Feminino , Povo Asiático , China/epidemiologia , Exercício Físico
18.
Acta Derm Venereol ; 104: adv23805, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38590175

RESUMO

ATP citrate lyase, the first rate-limiting enzyme in de novo lipogenesis, plays a crucial role in tumour progression. This study explores ATP citrate lyase's potential as a tumour biomarker and its role in cutaneous squamous cell carcinoma. ATP citrate lyase expression patterns were analysed using TCGA and TIMER databases, and patient skin specimens were collected for immunohistochemistry to determine ATP citrate lyase levels. Cell proliferation, cell cycle, apoptosis, and c-Myc expression were assessed in A431 and SCL-1 cells. Stable cell lines with reduced ATP citrate lyase expression were obtained and subcutaneously implanted into nude mice to evaluate in vivo tumour growth. Ki67, c-Myc expression and TUNEL staining were analysed in subcutaneous tumours. ATP citrate lyase exhibited upregulation in various tumours, and showed significant associations with prognosis and immune infiltrate. Moreover, ATP citrate lyase was highly expressed in cutaneous squamous cell carcinoma. After ATP citrate lyase silencing, cutaneous squamous cell carcinoma cell growth decelerated, the cell cycle halted, cell apoptosis increased, and c-Myc expression decreased. Animal experiments revealed that, following ATP citrate lyase knockdown, tumour tissue growth slowed down, and there was a reduction in Ki-67 and c-Myc expression, accompanied by enhanced TUNEL staining. In conclusion, ATP citrate lyase may serve as a tumour biomarker. It is highly expressed in cutaneous squamous cell carcinoma and may serve as a therapeutic target.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Camundongos , Animais , Humanos , ATP Citrato (pro-S)-Liase/genética , ATP Citrato (pro-S)-Liase/metabolismo , Carcinoma de Células Escamosas/genética , Biomarcadores Tumorais/genética , Camundongos Nus , Neoplasias Cutâneas/genética
19.
Water Res ; 255: 121550, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38579590

RESUMO

Electrochemistry is a sustainable technology for oil-water separation. In the common flat electrode scheme, due to a few centimeters away from the anode, oil droplets have to undergo electromigration to and electrical neutralization at the anodic surface before they coalesce into large oil droplets and rise to water surface, resulting in slow demulsification and easy anode fouling. Herein, a novel strategy is proposed on basis of a TiO2-x/Ti anode with microchannels to overcome these problems. When oil droplets with several microns in diameter flow through channels with tens of microns in diameter, the electromigration distance is shortened by three orders of magnitude, electrical neutralization is replaced by polarization coupling ·OH oxidation. The new strategy was supported by experimental results and theoretical analysis. Taking the suspension containing emulsified oil as targets, COD value dropped from initial 500 mg/L to 117 mg/L after flowing through anodic microchannels in only 58 s of running time, and the COD removal was 21 times higher than that for a plate anode. At similar COD removal, the residence time was 48 times shorter than that of reported flat electrodes. Coalescences of oil droplets in microchannels were observed by a confocal laser scanning microscopy. This new strategy opens a door for using microchannel electrodes to accelerate electrochemical coalescence of oil-in-water droplets.

20.
J Nanobiotechnology ; 22(1): 191, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637832

RESUMO

BACKGROUND: Exosomes assume a pivotal role as essential mediators of intercellular communication within tumor microenvironments. Within this context, long noncoding RNAs (LncRNAs) have been observed to be preferentially sorted into exosomes, thus exerting regulatory control over the initiation and progression of cancer through diverse mechanisms. RESULTS: Exosomes were successfully isolated from cholangiocarcinoma (CCA) CTCs organoid and healthy human serum. Notably, the LncRNA titin-antisense RNA1 (TTN-AS1) exhibited a conspicuous up-regulation within CCA CTCs organoid derived exosomes. Furthermore, a significant elevation of TTN-AS1 expression was observed in tumor tissues, as well as in blood and serum exosomes from patients afflicted with CCA. Importantly, this hightened TTN-AS1 expression in serum exosomes of CCA patients manifested a strong correlation with both lymph node metastasis and TNM staging. Remarkably, both CCA CTCs organoid-derived exosomes and CCA cells-derived exosomes featuring pronounced TTN-AS1 expression demonstrated the capability to the proliferation and migratory potential of CCA cells. Validation of these outcomes was conducted in vivo experiments. CONCLUSIONS: In conclusion, our study elucidating that CCA CTCs-derived exosomes possess the capacity to bolster the metastasis tendencies of CCA cells by transporting TTN-AS1. These observations underscore the potential of TTN-AS1 within CTCs-derived exosomes to serve as a promising biomarker for the diagnosis and therapeutic management of CCA.


Assuntos
Colangiocarcinoma , Exossomos , MicroRNAs , Células Neoplásicas Circulantes , RNA Bacteriano , RNA Longo não Codificante , Humanos , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Exossomos/metabolismo , Conectina/genética , Conectina/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Proliferação de Células , Movimento Celular , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral
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