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2.
Appl Microbiol Biotechnol ; 108(1): 402, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951204

RESUMO

Delayed graft function (DGF) is a frequently observed complication following kidney transplantation (KT). Our prior research revealed dynamic shifts in salivary microbiota post-KT with immediate graft function (IGF), yet its behavior during DGF remains unexplored. Five recipients with DGF and 35 recipients with IGF were enrolled. Saliva samples were collected during the perioperative period, and 16S rRNA gene sequencing was performed. The salivary microbiota of IGFs changed significantly and gradually stabilized with the recovery of renal function. The salivary microbiota composition of DGFs was significantly different from that of IGFs, although the trend of variation appeared to be similar to that of IGFs. Salivary microbiota that differed significantly between patients with DGF and IGF at 1 day after transplantation were able to accurately distinguish the two groups in the randomForest algorithm (accuracy = 0.8333, sensitivity = 0.7778, specificity = 1, and area under curve = 0.85), with Selenomonas playing an important role. Bacteroidales (Spearman's r = - 0.4872 and p = 0.0293) and Veillonella (Spearmen's r = - 0.5474 and p = 0.0125) were significantly associated with the serum creatinine in DGF patients. Moreover, the significant differences in overall salivary microbiota structure between DGF and IGF patients disappeared upon long-term follow-up. This is the first study to investigate the dynamic changes in salivary microbiota in DGFs. Our findings suggested that salivary microbiota was able to predict DGF in the early stages after kidney transplantation, which might help the perioperative clinical management and early-stage intervention of kidney transplant recipients. KEY POINTS: • Salivary microbiota on the first day after KT could predict DGF. • Alterations in salivary taxa after KT are related to recovery of renal function.


Assuntos
Função Retardada do Enxerto , Transplante de Rim , Microbiota , RNA Ribossômico 16S , Saliva , Humanos , Transplante de Rim/efeitos adversos , Saliva/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Adulto , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética
3.
Surg Endosc ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958719

RESUMO

BACKGROUND: Laparoscopic pancreatoduodenectomy (LPD) is one of the most challenging operations and has a long learning curve. Artificial intelligence (AI) automated surgical phase recognition in intraoperative videos has many potential applications in surgical education, helping shorten the learning curve, but no study has made this breakthrough in LPD. Herein, we aimed to build AI models to recognize the surgical phase in LPD and explore the performance characteristics of AI models. METHODS: Among 69 LPD videos from a single surgical team, we used 42 in the building group to establish the models and used the remaining 27 videos in the analysis group to assess the models' performance characteristics. We annotated 13 surgical phases of LPD, including 4 key phases and 9 necessary phases. Two minimal invasive pancreatic surgeons annotated all the videos. We built two AI models for the key phase and necessary phase recognition, based on convolutional neural networks. The overall performance of the AI models was determined mainly by mean average precision (mAP). RESULTS: Overall mAPs of the AI models in the test set of the building group were 89.7% and 84.7% for key phases and necessary phases, respectively. In the 27-video analysis group, overall mAPs were 86.8% and 71.2%, with maximum mAPs of 98.1% and 93.9%. We found commonalities between the error of model recognition and the differences of surgeon annotation, and the AI model exhibited bad performance in cases with anatomic variation or lesion involvement with adjacent organs. CONCLUSIONS: AI automated surgical phase recognition can be achieved in LPD, with outstanding performance in selective cases. This breakthrough may be the first step toward AI- and video-based surgical education in more complex surgeries.

4.
Bioresour Technol ; 406: 131060, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38950831

RESUMO

This study surveyed the fates of artificial sweeteners in influent, effluent, and sewage sludge (SS) in wastewater treatment plant, and investigated the effects of Micro-Kaolin (Micro-KL) and Nano-Kaolin (Nano-KL) on nitrogen transformation and sucralose (SUC) and acesulfame (ACE) degradation during SS composting. Results showed the cumulative rate of ACE and SUC in SS was ∼76 %. During SS composting, kaolin reduced NH3 emissions by 30.2-45.38 %, and N2O emissions by 38.4-38.9 %, while the Micro-KL and Nano-KL reduced nitrogen losses by 14.8 % and 12.5 %, respectively. Meanwhile, Micro-KL and Nano-KL increased ACE degradation by 76.8 % and 84.2 %, and SUC degradation by 75.3 % and 77.7 %, and significantly shifted microbial community structure. Furthermore, kaolin caused a positive association between Actinobacteria and sweetener degradation. Taken together, kaolin effectively inhibited nitrogen loss and promoted the degradation of ACE and SUC during the SS composting, which is of great significance for the removal of emerging organic pollutants in SS.


Assuntos
Compostagem , Caulim , Esgotos , Edulcorantes , Caulim/química , Esgotos/química , Compostagem/métodos , Águas Residuárias/química , Biodegradação Ambiental , Poluentes Químicos da Água , Purificação da Água/métodos , Nitrogênio , Nanopartículas/química , Sacarose/metabolismo , Sacarose/análogos & derivados
5.
Nat Commun ; 15(1): 6043, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025845

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.


Assuntos
Antígeno CD47 , Carcinoma Ductal Pancreático , Transição Epitelial-Mesenquimal , Armadilhas Extracelulares , Neoplasias Hepáticas , Macrófagos , Necroptose , Neoplasias Pancreáticas , Proteínas Quinases , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/metabolismo , Animais , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/genética , Camundongos , Macrófagos/metabolismo , Macrófagos/imunologia , Linhagem Celular Tumoral , Antígeno CD47/metabolismo , Antígeno CD47/genética , Proteínas Quinases/metabolismo , Armadilhas Extracelulares/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Masculino , Transdução de Sinais , Feminino , Acrilamidas , Sulfonamidas
6.
Int J Surg ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954668

RESUMO

BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) is a widely adopted surgical approach for benign and low-grade malignant neoplasms of the distal pancreas. The Kimura and Warshaw techniques represent two principal strategies, yet it still needs to be determined which one is superior. Our investigation aimed to evaluate the clinical outcomes associated with each technique. MATERIALS AND METHODS: This single-center, parallel-group, patient-blinded randomized controlled trial (RCT) was conducted at the XXXXX University. Stratified block randomization was utilized to enroll 114 patients starting in March 2022, with an interim analysis of short-term outcomes scheduled after 45%-50% of participant enrollment. Patients were randomized to receive LSPDP via either the Kimura or Warshaw technique. The primary endpoint was intraoperative blood loss, while secondary endpoints included a range of outcomes from composite outcome to quality of life, as quantified by the EQ-5D-5L. RESULTS: From March 2022 to November 2023, 53 patients were randomly allocated to the Kimura (n=25) or Warshaw (n=28) groups for LSPDP. Baseline characteristics and postoperative outcomes were similar between the groups, such as pancreatic fistula incidence, EQ-5D-5L index scores, and delayed gastric emptying rates. Per-protocol (PP) analysis revealed that the Kimura group experienced significantly less blood loss (52.5±51.6 mL vs. 91.7±113.5 mL, P=0.007) and a reduced rate of composite outcome (23.8% vs. 56.7%, P=0.019), but incurred higher costs in the Warshaw group (¥56,227.4±¥7,027.0 vs. ¥63,513.8±¥12,944.5, P=0.013). Splenic infarction rates were higher in the Warshaw group, though not statistically significant (ITT: 39.3% vs. 12.5%, P=0.058; PP: 36.7% vs. 14.3%, P=0.113), without necessitating intervention. Neither group experienced postpancreatectomy haemorrhage, 90-day mortality, or ICU admissions, and all postoperative complications were mild (Clavien-Dindo Grade

7.
Front Pharmacol ; 15: 1361628, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948477

RESUMO

Pancreatoblastoma (PB), a neoplasm derived from pancreatic follicular cells, primarily affects the pediatric population. Although infrequent in adults, it is associated with a considerably worse prognosis. Approximately one-third of patients are diagnosed with metastatic disease, with liver metastases being the most prevalent. Diagnosis relies on histopathological alterations including squamous vesicles, positive staining for CK8/CK18/CK19, and nuclear displacement of ß-catenin. Additionally, liver metastases demonstrate substantial enhancement during the arterial phase of a contrast-enhanced computed tomography (CT) scan. Surgical resection serves as the principal therapeutic approach for addressing primary lesions and liver metastatic PB. In instances where surgical intervention is not viable, patients may derive benefits from systemic therapy and radiotherapy. This particular case report presents the clinical details of a 27-year-old female patient diagnosed with PB, who subsequently developed multiple liver metastases following a pancreaticoduodenectomy. Genomic examinations revealed the presence of ERBB2 amplification, RAD54L deletion, low TMB-L, and MSS in the patient. Despite the patient undergoing chemotherapy and Her-2 targeted therapy in conjunction with immunotherapy, no reduction in lesion size was observed until the administration of surufatinib. Subsequently, a notable outcome ensued, where the metastatic lesions were effectively excised via surgical intervention. Surufatinib has demonstrated a progression-free survival (PFS) of no less than 14 months, and the patient's survival has endured for a duration of 33 months. This indicates the potential efficacy of surufatinib as a viable therapeutic alternative for adult patients afflicted with PB.

8.
MedComm (2020) ; 5(7): e623, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38988495

RESUMO

This study aimed to identify the role of chromothripsis as a novel biomarker in the prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms (pNENs). We conducted next-generation gene sequencing in a cohort of 30 patients with high-grade (G3) pNENs. As a reference, a similar analysis was also performed on 25 patients with low-grade (G1/G2) pancreatic neuroendocrine tumors (pNETs). Chromothripsis and its relationship with clinicopathological features and prognosis were investigated. The results showed that DNA damage response and repair gene alteration and TP53 mutation were found in 29 and 11 patients, respectively. A total of 14 out of 55 patients had chromothripsis involving different chromosomes. Chromothripsis had a close relationship with TP53 alteration and higher grade. In the entire cohort, chromothripsis was associated with a higher risk of distant metastasis; both chromothripsis and metastasis (ENETS Stage IV) suggested a significantly shorter overall survival (OS). Importantly, in the high-grade pNENs group, chromothripsis was the only independent prognostic indicator significantly associated with a shorter OS, other than TP53 alteration or pathological pancreatic neuroendocrine carcinomas (pNECs) diagnosis. Chromothripsis can guide worse prognosis in pNENs, and help differentiate pNECs from high-grade (G3) pNETs.

9.
Nano Lett ; 24(28): 8679-8686, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38949784

RESUMO

The simultaneous detection of the orbital angular momentum (OAM) and wavelength offers new opportunities for optical multiplexing. However, because of the dispersion of lens functions for Fourier transformation, the mode conversions at distinct wavelengths cannot be achieved in the same plane. Here we propose an ultracompact achromatic complementary metal oxide semiconductor (CMOS)-integrated OAM mode detector. Specifically, a spatial multiplexed scheme, randomly interleaving the phase distributions for distributing the superposed OAM modes into preset positions at distinct wavelengths, is presented. In addition, such a nanoprinted achromatic OAM detector featuring a microscale size and a short focal length can be integrated onto a CMOS chip. Consequently, the four-bit incident light beams at three discrete wavelengths (633, 532, and 488 nm) can be distinguished with a high degree of accuracy evaluated by the average standardized Euclidean distance of ∼0.75 between the analytical and target results. Our results showcase a miniaturized platform for achieving high-capacity information processing.

10.
Proc Natl Acad Sci U S A ; 121(28): e2401579121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38968123

RESUMO

Iron is an essential element for life owing to its ability to participate in a diverse array of oxidation-reduction reactions. However, misregulation of iron-dependent redox cycling can also produce oxidative stress, contributing to cell growth, proliferation, and death pathways underlying aging, cancer, neurodegeneration, and metabolic diseases. Fluorescent probes that selectively monitor loosely bound Fe(II) ions, termed the labile iron pool, are potentially powerful tools for studies of this metal nutrient; however, the dynamic spatiotemporal nature and potent fluorescence quenching capacity of these bioavailable metal stores pose challenges for their detection. Here, we report a tandem activity-based sensing and labeling strategy that enables imaging of labile iron pools in live cells through enhancement in cellular retention. Iron green-1 fluoromethyl (IG1-FM) reacts selectively with Fe(II) using an endoperoxide trigger to release a quinone methide dye for subsequent attachment to proximal biological nucleophiles, providing a permanent fluorescent stain at sites of elevated labile iron. IG1-FM imaging reveals that degradation of the major iron storage protein ferritin through ferritinophagy expands the labile iron pool, while activation of nuclear factor-erythroid 2-related factor 2 (NRF2) antioxidant response elements (AREs) depletes it. We further show that lung cancer cells with heightened NRF2 activation, and thus lower basal labile iron, have reduced viability when treated with an iron chelator. By connecting labile iron pools and NRF2-ARE activity to a druggable metal-dependent vulnerability in cancer, this work provides a starting point for broader investigations into the roles of transition metal and antioxidant signaling pathways in health and disease.


Assuntos
Elementos de Resposta Antioxidante , Ferro , Humanos , Ferro/metabolismo , Corantes Fluorescentes/química , Fator 2 Relacionado a NF-E2/metabolismo , Ferritinas/metabolismo , Estresse Oxidativo , Oxirredução , Linhagem Celular Tumoral , Antioxidantes/metabolismo
11.
BMJ Open ; 14(7): e084274, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013651

RESUMO

INTRODUCTION: Patients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours, its application in treating PDAC is limited. Recent studies have indicated that chemotherapy or stereotactic body radiotherapy (SBRT) may improve the antitumour effect of PD-1 blockade in patients with PDAC. The objective of this study is to evaluate the efficacy and safety of combined therapy comprising PD-1 blockade, gemcitabine plus nab-paclitaxel chemotherapy and SBRT for patients with metastatic PDAC. METHODS AND ANALYSIS: This is a multicentre, single-arm, prospective phase II clinical trial. Forty-three patients diagnosed with metastatic PDAC will be enrolled. The eligible patients will be intravenously administered 1000 mg/m2 gemcitabine and 125 mg/m2 nab-paclitaxel on days 1 and 8 of the 21-day cycle. Serplulimab (200 mg) will be administered intravenously on day 1 of the 21-day cycle. Furthermore, during the second cycle, the patients will undergo SBRT with doses of 33 Gy in five fractions for primary lesions or doses of 24 Gy in three fractions for metastases. The primary endpoint is the 6-month progression-free survival (PFS) rate. The secondary endpoints overall survival, PFS, overall response rate, disease control rate, time to progression, duration of response, duration of disease control and safety. Moreover, this trial seeks to investigate biomarkers such as circulating tumour DNA and circulating hybrid cells in patients diagnosed with metastatic PDAC. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300073237.


Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Gencitabina , Paclitaxel , Neoplasias Pancreáticas , Radiocirurgia , Humanos , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Albuminas/uso terapêutico , Albuminas/administração & dosagem , Radiocirurgia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , Idoso , Adulto , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como Assunto , Terapia Combinada , Intervalo Livre de Progressão
12.
Immun Inflamm Dis ; 12(6): e1310, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888464

RESUMO

BACKGROUND: The PI3K/Akt/mTOR pathway and autophagy are important physiological processes. But their roles in eCRSwNP remains controversial. METHODS: In this study, we used the eCRSwNP mouse model, PI3K/Akt/mTOR pathway inhibitors, and autophagy inhibitors and activators to investigate the regulatory effects of the PI3K/Akt/mTOR pathway on autophagy, and their effects on eosinophilic inflammation, and tissue remodeling. The role of ILC2s in eCRSwNP was also studied, and the relationship between ILC2s and autophagy was preliminarily determined. RESULTS: Our results show that eosinophilic inflammation in eCRSwNP mice could be inhibited by promoting the autophagy; otherwise, eosinophilic inflammation could be promoted. Meanwhile, inhibition of the PI3K/Akt/mTOR pathway can further promote autophagy and inhibit eosinophilic inflammation. Meanwhile, inhibiting the PI3K/Akt/mTOR pathway and promoting autophagy can reduce the number of ILC2s and the severity of tissue remodeling in the nasal polyps of eCRSwNP mice. CONCLUSIONS: We conclude that the PI3K/Akt/mTOR pathway plays roles in eosinophilic inflammation and tissue remodeling of eCRSwNP, in part by regulating the level of autophagy. The downregulation of autophagy is a pathogenesis of eCRSwNP; therefore, the recovery of normal autophagy levels might be a new target for eCRSwNP therapy. Furthermore, autophagy might inhibit eosinophilic inflammation and tissue remodeling, in part by reducing the number of ILC2s.


Assuntos
Autofagia , Imunidade Inata , Linfócitos , Pólipos Nasais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Sinusite , Serina-Treonina Quinases TOR , Animais , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Sinusite/imunologia , Sinusite/patologia , Sinusite/metabolismo , Autofagia/imunologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Doença Crônica , Pólipos Nasais/imunologia , Pólipos Nasais/patologia , Modelos Animais de Doenças , Eosinofilia/imunologia , Eosinofilia/patologia , Eosinófilos/imunologia , Eosinófilos/patologia , Eosinófilos/metabolismo , Camundongos Endogâmicos BALB C
13.
Imeta ; 3(1): e158, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38868515

RESUMO

Antimicrobial resistance (AMR) is a major threat to global public health, and antibiotic resistance genes (ARGs) are widely distributed across humans, animals, and environment. Farming environments are emerging as a key research area for ARGs and antibiotic resistant bacteria (ARB). While the skin is an important reservoir of ARGs and ARB, transmission mechanisms between farming environments and human skin remain unclear. Previous studies confirmed that swine farm environmental exposures alter skin microbiome, but the timeline of these changes is ill defined. To improve understanding of these changes and to determine the specific time, we designed a cohort study of swine farm workers and students through collected skin and environmental samples to explore the impact of daily occupational exposure in swine farm on human skin microbiome. Results indicated that exposure to livestock-associated environments where microorganisms are richer than school environment can reshape the human skin microbiome and antibiotic resistome. Exposure of 5 h was sufficient to modify the microbiome and ARG structure in workers' skin by enriching microorganisms and ARGs. These changes were preserved once formed. Further analysis indicated that ARGs carried by host microorganisms may transfer between the environment with workers' skin and have the potential to expand to the general population using farm workers as an ARG vector. These results raised concerns about potential transmission of ARGs to the broader community. Therefore, it is necessary to take corresponding intervention measures in the production process to reduce the possibility of ARGs and ARB transmission.

14.
Nat Commun ; 15(1): 4870, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849333

RESUMO

Critical challenges remain in clinical translation of extracellular vesicle (EV)-based therapeutics due to the absence of methods to enrich cells with high EV secretion. Current cell sorting methods are limited to surface markers that are uncorrelated to EV secretion or therapeutic potential. Here, we utilize a nanovial technology for enrichment of millions of single cells based on EV secretion. This approach is applied to select mesenchymal stem cells (MSCs) with high EV secretion as therapeutic cells for improving treatment. The selected MSCs exhibit distinct transcriptional profiles associated with EV biogenesis and vascular regeneration and maintain high levels of EV secretion after sorting and regrowth. In a mouse model of myocardial infarction, treatment with high-secreting MSCs improves heart functions compared to treatment with low-secreting MSCs. These findings highlight the therapeutic importance of EV secretion in regenerative cell therapies and suggest that selecting cells based on EV secretion could enhance therapeutic efficacy.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Infarto do Miocárdio , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/transplante , Animais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos , Infarto do Miocárdio/terapia , Infarto do Miocárdio/metabolismo , Humanos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Separação Celular/métodos , Masculino
15.
Medicine (Baltimore) ; 103(25): e38567, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905409

RESUMO

BACKGROUND: Our previous studies showed that laser moxibustion may be effective in alleviating the symptoms of knee osteoarthritis. However, the therapeutic effect in patients with different Kellgren-Lawrence (KL) grades is still unclear. We aimed to compare the efficacy of laser moxibustion in the treatment of knee osteoarthritis with different KL grades. METHODS: A total of 392 symptomatic KOA patients with different KL grades were randomly assigned to the laser treatment or sham laser control group (1:1). The patients received laser moxibustion treatment or sham treatment 3 times a week for 4 weeks. Outcomes were measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and Visual Analog Scale (VAS) scores, and the primary outcome measurement was the change in WOMAC pain scores from baseline to week 4. RESULTS: Among 392 randomized participants, 364 (92.86%) completed the trial. Participants with KL grades 2, 3, and 4 had significantly higher pain, functional, and total WOMAC scores than those with KL grade 1. Spearman correlation test results showed a positive correlation between KL grade and WOMAC pain, function, stiffness scores, and WOMAC total scores. That is, the higher the KL grade, the higher the WOMAC pain, function, stiffness, and WOMAC total scores. After 4 weeks of treatment, patients with KL grades 2 and 3 had significantly higher improvement scores in pain, function, and total scores than those with KL grade 1, whereas those with KL grade 2 had significantly higher improvement scores in stiffness than those with KL grade 1. Patients with KL grade 4 showed no significant effects after laser moxibustion treatment. CONCLUSION: Laser moxibustion is effective for pain reduction and functional improvement in the treatment of KOA with KL grades 2 and 3.


Assuntos
Moxibustão , Osteoartrite do Joelho , Medição da Dor , Humanos , Osteoartrite do Joelho/terapia , Moxibustão/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Índice de Gravidade de Doença , Terapia a Laser/métodos
16.
Adv Sci (Weinh) ; : e2402838, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896788

RESUMO

Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine-selective warheads face challenges due to cross-reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro- or phenoxy-substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy-NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH-overexpressed cancer cells. Conversely, alkoxy-NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti-interfering ability against thiols. Leveraging a proximity-driven approach, alkoxy-NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins.

17.
World J Clin Cases ; 12(17): 3271-3276, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38898839

RESUMO

BACKGROUND: Primary nasal tuberculosis (TB) is a rare form of extrapulmonary TB, particularly in patients receiving anti-tumor necrosis factor (TNF) immunotherapy. As a result, its diagnosis remains challenging. CASE SUMMARY: A 58-year-old male patient presented to the ear, nose, and throat department with right-sided nasal obstruction and bloody discharge for 1 month. He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation. Biopsy findings revealed chronic granulomatous inflammation and a few acid-fast bacilli, suggestive of primary nasal TB. He was referred to our TB management department for treatment with oral anti-TB agents. After 9 months, the nasal lesions had disappeared. No recurrence was noted during follow-up. CONCLUSION: The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate, particularly when pathological findings suggest granulomatous inflammation.

18.
Nucl Med Commun ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38832427

RESUMO

METHODS: This prospective study included 92 patients who underwent BLVR with quantitative SPECT/CT study pre- and post-procedure between November 2018 and June 2023. The mean age was 70 years (range 56-85). with 51 males and 41 females. SPECT/CT quantified perfusion for each lobe, and the lowest counts/volume ratio determined the procedural target. Postprocedure SPECT/CT assessed total atelectasis and perfusion shifts. The 6-minute walk test and pulmonary function tests were compared pre- and post-BLVR. RESULTS: SPECT/CT-guided BLVR showed clinical benefits (decreased oxygen requirements) and physiological improvements in total lung capacity, forced expiratory volume, and forced vital capacity (P < 0.05). Significant perfusion shifts were observed away from the target lobe, with unique patterns noted for ipsilateral and contralateral nontarget lobes (P < 0.05). CONCLUSION: Quantitative lobar SPECT/CT in preprocedural guidance for BLVR proved useful in identifying suitable targets in multi-lobe homogeneous emphysema, resulting in physiological and clinical improvements for this patient group. The perfusion shift information provided by SPECT/CT offers valuable insights for pulmonologists.

19.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38725156

RESUMO

Protein acetylation is one of the extensively studied post-translational modifications (PTMs) due to its significant roles across a myriad of biological processes. Although many computational tools for acetylation site identification have been developed, there is a lack of benchmark dataset and bespoke predictors for non-histone acetylation site prediction. To address these problems, we have contributed to both dataset creation and predictor benchmark in this study. First, we construct a non-histone acetylation site benchmark dataset, namely NHAC, which includes 11 subsets according to the sequence length ranging from 11 to 61 amino acids. There are totally 886 positive samples and 4707 negative samples for each sequence length. Secondly, we propose TransPTM, a transformer-based neural network model for non-histone acetylation site predication. During the data representation phase, per-residue contextualized embeddings are extracted using ProtT5 (an existing pre-trained protein language model). This is followed by the implementation of a graph neural network framework, which consists of three TransformerConv layers for feature extraction and a multilayer perceptron module for classification. The benchmark results reflect that TransPTM has the competitive performance for non-histone acetylation site prediction over three state-of-the-art tools. It improves our comprehension on the PTM mechanism and provides a theoretical basis for developing drug targets for diseases. Moreover, the created PTM datasets fills the gap in non-histone acetylation site datasets and is beneficial to the related communities. The related source code and data utilized by TransPTM are accessible at https://www.github.com/TransPTM/TransPTM.


Assuntos
Redes Neurais de Computação , Processamento de Proteína Pós-Traducional , Acetilação , Biologia Computacional/métodos , Bases de Dados de Proteínas , Software , Algoritmos , Humanos , Proteínas/química , Proteínas/metabolismo
20.
JTCVS Open ; 18: 400-406, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38690443

RESUMO

Objective: To investigate the impact of donor-recipient (DR) sex matches on survival after lung transplantation while controlling for size difference in the United Network of Organ Sharing (UNOS) database. Methods: We performed a retrospective study of 27,423 lung transplant recipients who were reported in the UNOS database (January 2005-March 2020). Patients were divided into groups based on their respective DR sex match: male to male (MM), male to female (MF), female to female, (FF), and female to male (FM). Kaplan-Meier curve and Cox regression with log-rank tests were used to assess 1-, 3-, 5-, and 10-year survival. We also modeled survival for each group after controlling for size-related variables via the Cox regression. Results: Kaplan-Meier curves showed overall significance at 1-, 3-, 5-, and 10-year end points (P < .0001). Estimated median survival time based on Kaplan-Meier analysis were 6.41 ± 0.15, 6.13 ± 0.18, 5.86 ± 0.10, and 5.37 ± 0.17 years for FF, MF, MM, and FM, respectively (P < .0001). After we controlled for size differences, FF had statistically significantly longer 5- and 10-year survival than all other cohorts. MF also had statistically significantly longer 5- and 10-year survival than FM. Conclusions: When variables associated with size were controlled for, FF had improved survival than other DR groups. A female recipient may experience longer survival with a female donor's lungs versus a male donor's lungs of similar size.

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