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1.
Medicine (Baltimore) ; 103(28): e38710, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996153

RESUMO

PURPOSE: Postoperative shivering (POS) is a common and vital complication after anesthesia, which may result in serious consequences and uncomfortable experiences. Acetaminophen has been used to treat fever and mild to moderate pain. However, there is not enough evidence to prove its advantage for POS. This meta-analysis aimed to explore the prophylactic use of acetaminophen as a valid agent for POS. METHODS: Two researchers independently searched PubMed, the Cochrane Library, and Embase for controlled clinical trials. The meta-analysis of randomized controlled trials (RCTs) was performed by Review Manager. RESULTS: Nine trials with 856 patients were included in our meta-analysis. Acetaminophen significantly reduced POS compared with placebo (pooled risk ratio [RR]: 0.43, 95% confidence interval [CI]: 0.35-0.52). What is more, not only 15 mg/kg but also 1000 mg intravenous acetaminophen could reduce the incidence of shivering compared with placebo. CONCLUSION: Our present meta-analysis demonstrates that the intravenous prophylactic infusion of acetaminophen may prevent POS, and the results may provide new evidence to expand the clinical value of acetaminophen in addition to its routine usage.


Assuntos
Acetaminofen , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Estremecimento , Estremecimento/efeitos dos fármacos , Humanos , Acetaminofen/administração & dosagem , Acetaminofen/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/tratamento farmacológico , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/uso terapêutico , Infusões Intravenosas , Administração Intravenosa
2.
Int J Colorectal Dis ; 39(1): 107, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001900

RESUMO

PURPOSE: Family history is one of the strongest risk factors for inflammatory bowel diseases (IBD) while studies about the clinical phenotype of familial IBD are limited. This study aimed to compare the phenotypic features of familial Crohn's disease (CD) with sporadic CD. METHODS: Familial CD was defined as CD patients having one or more first, second, third, fourth degree, or above relatives with CD. Sporadic CD patients hospitalized during the same period were matched 1:3 by age and gender. Differences in clinical characteristics, phenotype distribution, extraintestinal manifestations, and complications at diagnosis, as well as treatment regimen and surgery, were compared between familial and sporadic CD. RESULTS: The familial CD was associated with a higher rate of past appendectomy history (P = 0.009), more intestinal perforation at onset (P = 0.012), more MRI results of anal lesion (P = 0.023), and gastrointestinal perforation (P = 0.040) at diagnosis, higher rate of past intestinal surgery history (P = 0.007), more number of intestinal surgeries (P = 0.037), longer duration of follow-up (P = 0.017), lower rate of taking biologicals for current maintenance (P = 0.043), lower tendency to upgrade to biologicals during follow-up (P = 0.013), higher possibility to experience gastrointestinal obstruction (P = 0.047), and abdominal abscess during follow-up (P = 0.045). CONCLUSION: Familial CD is associated with a more aggressive clinical phenotype.


Assuntos
Doença de Crohn , Fenótipo , Humanos , Doença de Crohn/genética , Doença de Crohn/complicações , Doença de Crohn/patologia , Masculino , Feminino , China , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Predisposição Genética para Doença , Fatores de Risco , Adolescente
3.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167349, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39002703

RESUMO

Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling. Epithelial-mesenchymal transition (EMT) of bronchial epithelial cells is considered to be a crucial player in asthma. Methyltransferase-like 14 (METTL14), an RNA methyltransferase, is implicated in multiple pathological processes, including EMT, cell proliferation and migration. However, the role of METTL14 in asthma remains uncertain. This research aimed to explore the biological functions of METTL14 in asthma and its underlying upstream mechanisms. METTL14 expression was down-regulated in asthmatic from three GEO datasets (GSE104468, GSE165934, and GSE74986). Consistent with this trend, METTL14 was decreased in the lung tissues of OVA-induced asthmatic mice and transforming growth factor-ß1 (TGF-ß1)-stimulated human bronchial epithelial cells (Beas-2B) in this study. Overexpression of METTL14 caused reduction in mesenchymal markers (FN1, N-cad, Col-1 and α-SMA) in TGF-ß1-treated cells, but caused increase in epithelial markers (E-cad), thus inhibiting EMT. Also, METTL14 suppressed the proliferation and migration ability of TGF-ß1-treated Beas-2B cells. Two transcription factors, ETS1 and RBPJ, could both bind to the promoter region of METTL14 and drive its expression. Elevating METTL14 expression could reversed EMT, cell proliferation and migration promoted by ETS1 or RBPJ deficiency. These results indicate that the ETS1/METTL14 and RBPJ/METTL14 transcription axes exhibit anti-EMT, anti-proliferation and anti-migration functions in TGF-ß1-induced bronchial epithelial cells, implying that METTL14 may be considered an alternative candidate target for the treatment of asthma.

4.
Clin Res Hepatol Gastroenterol ; : 102427, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39069261

RESUMO

With the continuous advancements of laparoscopic techniques, many surgeons have enhanced the feasibility and safety of this approach for carefully selected patients. This study aims to offer a comprehensive account of the technical aspects and surgical outcomes associated with laparoscopic anatomical right hepatectomy, explicitly utilizing a four-incision anterior approach. The surgical procedure involved several maneuvers, including blocking the Glissonean pedicle, ligation of the right hepatic artery, right branch of the portal vein, and the right hepatic duct, removal of the liver parenchyma along the ischemic line, and determination of the liver section based on four anatomical landmarks: the right anterior Glissonian pedicle, middle hepatic vein, root of the right hepatic vein, and retrohepatic inferior vena cava. The article provides clear visualization of these anatomical landmarks following right hepatectomy. Proper patient positioning and precise incision placement are crucial factors for ensuring the success of the laparoscopic right anterior hepatectomy procedure. The separation of the extrahepatic Glissonean pedicle at the liver hilum to determine the hepatic resection ischemia line, as well as the identification of liver sections using four anatomical landmarks are essential steps in the liver resection process. The laparoscopic anatomical right hepatectomy using a four-incision anterior approach was performed smoothly, with standard intraoperative techniques completed. Measures are in place to address any complications that may arise during the surgery.

5.
N Engl J Med ; 391(3): 213-223, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39018531

RESUMO

BACKGROUND: The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown. METHODS: In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn's disease who had had an inadequate response to anti-tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn's Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab. RESULTS: In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn's disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.).


Assuntos
Anticorpos Monoclonais , Doença de Crohn , Indução de Remissão , Ustekinumab , Humanos , Doença de Crohn/tratamento farmacológico , Ustekinumab/uso terapêutico , Ustekinumab/efeitos adversos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Índice de Gravidade de Doença , Análise de Intenção de Tratamento , Adulto Jovem
6.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1242-1250, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38886422

RESUMO

In this study, we used a high-throughput sequencing technology to survey the dry-wet seasonal change characteristics of soil ammonia-oxidizing bacteria (AOB) communities in the three restoration stages [i.e., Mallotus paniculatus community (early stage), Millettia leptobotrya community (middle stage), and Syzygium oblatum community (later stage)] of Xishuangbanna tropical forest ecosystems. We analyzed the effects of soil physicochemical characteristics on AOB community composition and diversity during tropical forest restoration. The results showed that tropical forest restoration significantly affected the relative abundance of dominant AOB phyla and their dry-wet seasonal variation. The maximum relative abundance of Proteobacteria (71.3%) was found in the early recovery stage, while that of Actinobacteria was found in the late recovery stage (1.0%). The abundances of Proteobacteria and Actinobacteria had the maximum ranges of dry-wet seasonal variation in the early and late stages, respectively. The abundance of dominant AOB genera and its dry-wet seasonal variation varied across tropical forest restoration stages. The maximum average relative abundance of Nitrosospira and Nitrosomonas in the late recovery stage was 66.2% and 1.5%, respectively. In contrast, the abundance of Nitrosovibrio reached its maximum (25.6%) in the early recovery stage. The maximum dry-wet seasonal variation in relative abundance of Nitrosospira and Nitrosomonas occurred in the early recovery stage, while that of Nitrosovibrio occurred in the middle recovery stage. The Chao1, Shannon, and Simpson diversity indices of AOB communities increased along the restoration stages, which were significantly higher in the wet season than in the dry season. The results of canonical correspondence analysis showed that soil easily oxidized carbon was the main factor controlling AOB community diversity and Actinobacteria abundance. Soil bulk density and temperature were the main factors affecting Proteobacteria abundance. Soil pH, microbial biomass carbon, water content, ammonium nitrogen, bulk density, and temperature were the main factors controlling the abundances of Nitrosospira, Nitrosomonas, and Nitrosovibrio. Therefore, tropical forest restoration can regulate the change of relative abundance of dominant AOB taxa via mediating the changes of soil temperature, bulk density, and readily oxidized carbon, leading to an increase in soil AOB community diversity.


Assuntos
Amônia , Bactérias , Florestas , Oxirredução , Estações do Ano , Microbiologia do Solo , Clima Tropical , Amônia/metabolismo , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Proteobactérias/isolamento & purificação , Proteobactérias/classificação , Proteobactérias/metabolismo , Proteobactérias/genética , China , Conservação dos Recursos Naturais , Recuperação e Remediação Ambiental/métodos , Nitrosomonas/metabolismo , Nitrosomonas/classificação , Nitrosomonas/crescimento & desenvolvimento , Floresta Úmida
7.
Chem Sci ; 15(25): 9756-9774, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38939132

RESUMO

G-quadruplexes (G4s) are atypical nucleic acid structures involved in basic human biological processes and are regulated by small molecules. To date, pyridostatin and its derivatives [e.g., PyPDS (4-(2-aminoethoxy)-N 2,N 6-bis(4-(2-(pyrrolidin-1-yl) ethoxy) quinolin-2-yl) pyridine-2,6-dicarboxamide)] are the most widely used G4-binding small molecules and considered to have the best G4 specificity, which provides a new option for the development of cisplatin-binding DNA. By combining PyPDS with cisplatin and its analogs, we synthesize three platinum complexes, named PyPDSplatins. We found that cisplatin with PyPDS (CP) exhibits stronger specificity for covalent binding to G4 domains even in the presence of large amounts of dsDNA compared with PyPDS either extracellularly or intracellularly. Multiomics analysis reveals that CP can effectively regulate G4 functions, directly damage G4 structures, activate multiple antitumor signaling pathways, including the typical cGAS-STING pathway and AIM2-ASC pathway, trigger a strong immune response and lead to potent antitumor effects. These findings reflect that cisplatin-conjugated specific G4 targeting groups have antitumor mechanisms different from those of classic cisplatin and provide new strategies for the antitumor immunity of metals.

8.
Nat Commun ; 15(1): 5435, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937504

RESUMO

Optical spatiotemporal vortices with transverse photon orbital angular momentum (OAM) have recently become a focal point of research. In this work we theoretically and experimentally investigate optical spatiotemporal vortices with radial and azimuthal quantum numbers, known as spatiotemporal Laguerre-Gaussian (STLG) wavepackets. These 3D wavepackets exhibit phase singularities and cylinder-shaped edge dislocations, resulting in a multi-ring topology in its spatiotemporal profile. Unlike conventional ST optical vortices, STLG wavepackets with non-zero p and l values carry a composite transverse OAM consisting of two directionally opposite components. We further demonstrate mode conversion between an STLG wavepacket and an ST Hermite-Gaussian (STHG) wavepacket through the application of strong spatiotemporal astigmatism. The converted STHG wavepacket is de-coupled in intensity in space-time domain that can be utilized to implement the efficient and accurate recognition of ultrafast STLG wavepackets carried various p and l . This study may offer new insights into high-dimensional quantum information, photonic topology, and nonlinear optics, while promising potential applications in other wave phenomena such as acoustics and electron waves.

9.
Sci Rep ; 14(1): 13592, 2024 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867002

RESUMO

Although aspirin can reduce the incidence of colorectal cancer (CRC), there is still uncertainty about its significance as a treatment for CRC, and the mechanism of aspirin in CRC is not well understood. In this study, we used aspirin to prevent AOM/DSS-induced CRC in mice, and the anti-CRC efficacy of aspirin was assessed using haematoxylin and eosin (H&E) staining and by determining the mouse survival rate and tumour size. 16S rDNA sequencing, flow cytometry (FCM), and Western blotting were also conducted to investigate the changes in the gut microbiota, tumour immune microenvironment, and apoptotic proteins, respectively. The results demonstrated that aspirin significantly exerted anti-CRC effects in mice. According to 16S rDNA sequencing, aspirin regulated the composition of the gut microbiota and dramatically reduced the abundance of Enterococcus cecorum. FCM demonstrated that there were more CD155 tumour cells and CD4 + CD25 + Treg cells showed increased TIGIT levels. Moreover, increased TIGIT expression on Treg cells is associated with reduced Treg cell functionality. Importantly, the inhibition of Treg cells is accompanied by the promotion of CD19 + GL-7 + B cells, CD8 + T cells, CD4 + CCR4 + Th2 cells, and CD4 + CCR6 + Th17 cells. Overall, aspirin prevents colorectal cancer by regulating the abundance of Enterococcus cecorum and TIGIT + Treg cells.


Assuntos
Aspirina , Neoplasias Colorretais , Microbioma Gastrointestinal , Receptores Imunológicos , Linfócitos T Reguladores , Aspirina/farmacologia , Animais , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/microbiologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Camundongos , Receptores Imunológicos/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Enterococcus/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL
10.
Biomed Pharmacother ; 177: 116982, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38906019

RESUMO

Lactylation is a novel post-translational modification (PTM) involving proteins that is induced by lactate accumulation. Histone lysine lactylation alters chromatin spatial configuration, influencing gene transcription and regulating the expression of associated genes. This modification plays a crucial role as an epigenetic regulatory factor in the progression of various diseases. Glycolytic reprogramming is one of the most extensively studied forms of metabolic reprogramming, recognized as a key hallmark of cancer cells. It is characterized by an increase in glycolysis and the inhibition of the tricarboxylic acid (TCA) cycle, accompanied by significant lactate production and accumulation. The two processes are closely linked by lactate, which interacts in various physiological and pathological processes. On the one hand, lactylation levels generally correlate positively with the extent of glycolytic reprogramming, being directly influenced by the lactate concentration produced during glycolytic reprogramming. On the other hand, lactylation can also regulate glycolytic pathways by affecting the transcription and structural functions of essential glycolytic enzymes. This review comprehensively outlines the mechanisms of lactylation and glycolytic reprogramming and their interactions in tumor progression, immunity, and inflammation, with the aim of elucidating the relationship between glycolytic reprogramming and lactylation.


Assuntos
Glicólise , Neoplasias , Processamento de Proteína Pós-Traducional , Humanos , Animais , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Ácido Láctico/metabolismo , Reprogramação Celular , Histonas/metabolismo , Inflamação/metabolismo
11.
Sleep Med ; 120: 34-43, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38865787

RESUMO

BACKGROUND AND OBJECTIVE: Epidemiological studies have shown that sleep disorders are risk factors for Alzheimer's disease (AD), but the causal relationship between sleep disorders and AD risk is unknown. We aim to assess the potential genetic causal association between sleep characteristics and AD, which may contribute to early identification and prediction of risk factors for AD. METHODS: Seven sleep-related traits and the outcome phenotype AD were selected from published genome-wide association studies (GWASs). These sleep-related characteristics and instrumental variables (IVs) for AD were extracted. Two-sample and multivariate Mendelian randomization (MR) analyses were performed to assess the causal relationships between sleep characteristics and AD. The inverse variance weighted (IVW), weighted median (WME), weighted mode (WM), MR-Egger regression (MR-Egger) and simple mode (SM) models were used to evaluate causality. The existence of pleiotropy was detected and corrected by MR-Egger regression, MR pleiotropy residuals and outliers. RESULTS: A two-sample MR study revealed a positive causal association between sleep duration and the onset of AD (OR = 1.002, 95 % CI: 1.000-1.004), and the risk of AD increased with increasing sleep duration. The MR-Egger regression method and MR-PRESSO were used to identify and correct pleiotropy, indicating that there was no horizontal pleiotropy. Heterogeneity was evaluated by Cochran's Q, which indicated no heterogeneity. In a multivariate MR study with seven sleep characteristics corrected for each other, we found that sleep duration remained causally associated with AD (OR = 1.004, 95 % CI: 1.000-1.007). Moreover, we found that after mutual correction, daytime napping had a causal relationship with the onset of AD, and daytime napping may reduce the risk of AD (OR = 0.995, 95 % CI: 0.991-1.000). CONCLUSION: This study is helpful for the early identification and prediction of risk factors for AD, long sleep durations are a risk factor for AD, and daytime napping can reduce the risk of AD.


Assuntos
Doença de Alzheimer , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Transtornos do Sono-Vigília , Doença de Alzheimer/genética , Doença de Alzheimer/epidemiologia , Humanos , Transtornos do Sono-Vigília/genética , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/complicações , Fatores de Risco , Causalidade
12.
Clin Chim Acta ; 560: 119754, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38815665

RESUMO

Syphilis, a sexually transmitted infection caused by Treponema pallidum, has been experiencing a rise in prevalence in recent years. "Syphilis serofast" describes a unique serological reaction in patients with syphilis whose clinical symptoms have resolved following consistent anti-syphilitic therapy, but the non-Treponema pallidum antigen serologic test is still positive. Syphilis serofast is a risk factor for syphilis recurrence, neurosyphilis, and multisystem involvement. Considering the current lack of comprehensive knowledge about the epidemiological characteristics, pathogenesis, and therapies of syphilis serofast, we conducted an online search of research relating to syphilis serofast over the last twenty years. Previous research has shown that the pathogenesis of syphilis serofast is mainly related to clinical factors, immune factors, syphilis subtypes, and T.pallidum membrane protein repeat gene antigen. There are two distinct viewpoints on the treatment of serofast: no excessive treatment and active treatment. In addition, serofast patients also showed two clinical outcomes: syphilis recurrence and persistent serofast status. This article systematically reviews the related factors, treatment, and clinical outcomes of syphilis serofast, provides a theoretical basis for its research, diagnosis, and treatment, and helps clinicians develop a follow-up treatment management plan for syphilis serofast.


Assuntos
Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Treponema pallidum/imunologia , Sorodiagnóstico da Sífilis
13.
J Leukoc Biol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748684

RESUMO

Neutrophils are essential cells involved in inflammation. However, the specific mechanism of neutrophil chemotaxis induced by Treponema Pallidum (T. pallidum) remains unknow. In this study, human umbilical vein endothelial cells (HUVECs) were utilized as target cells to investigate the expression levels of chemokines when stimulated with different concentrations of Tp0768(also known as TpN44.5 or TmpA, a T. pallidum infection dependent antigen). The results indicated that Tp0768 treatment enhanced neutrophil chemotaxis in HUVECs, which was closely associated with the expression levels of CXCL1(C-X-C Motif Chemokine Ligand 1), CXCL2(C-X-C Motif Chemokine Ligand 2), and CXCL8(C-X-C Motif Chemokine Ligand 8, also known as interleukin-8). At the same time, the results show that Toll Like Receptor 2 (TLR2) signaling pathway is activated and endoplasmic reticulum stress (ER stress) occurs. Furthermore, the findings revealed that the use of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and Immunoglobulin-Regulated Enhancer 1 (IRE1) inhibitors reduced the expression levels of CXCL1, CXCL2, and CXCL8. Additionally, inhibiting TLR2 significantly decreased the expression levels of ER stress-related proteins (PERK and IRE1), CXCL1, CXCL2, and CXCL8. Consequently, neutrophil chemotaxis was significantly inhibited after treatment with TLR2, PERK, and IRE1 inhibitors. These findings shed light on the role of Tp0768 in enhancing neutrophil chemotaxis in endothelial cells, providing a foundation for further exploration of syphilis pathogenesis and offering a new direction for the diagnosis and treatment of T. pallidum infection.

14.
Ther Adv Chronic Dis ; 15: 20406223241247648, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726235

RESUMO

In 2020, the European Medicines Agency approved subcutaneous (SC) vedolizumab (VDZ) for the maintenance treatment of adult patients with moderate to severe inflammatory bowel disease (IBD). This article reviews the efficacy, safety, persistence, pharmacology, patient satisfaction, and economic implications of transitioning to SC VDZ treatment and explores whether SC formulations can be recommended by the same guidelines as intravenous (IV) formulations. Clinical trials and real-world evidence indicate that transitioning from IV to SC VDZ in patients with IBD maintains clinical, biochemical, and patient-reported clinical remission and is well-tolerated, with no new safety issues identified, except for injection site reactions. Moreover, SC VDZ has an exposure-response relationship and low immunogenicity, is economical, and provides a high level of patient satisfaction. Owing to these advantages, transitioning may be advisable. In the future, more studies are needed to clarify the exact role of SC VDZ in IBD treatment, including optimization and transitioning strategies and individualized treatments based on baseline characteristics.


Subcutaneous vedolizumab for inflammatory bowel disease Transitioning from intravenous to subcutaneous vedolizumab (SC VDZ) in patients with inflammatory bowel disease maintains clinical, biochemical, and patient-reported clinical remission and is well-tolerated, with no new safety issues identified, except for injection site reactions. Moreover, SC VDZ has an exposure-response relationship and low immunogenicity, is economical, and provides a high level of patient satisfaction. Owing to these advantages, transitioning may be advisable.

15.
Nat Commun ; 15(1): 3782, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710678

RESUMO

Thermoelectrics have great potential for use in waste heat recovery to improve energy utilization. Moreover, serving as a solid-state heat pump, they have found practical application in cooling electronic products. Nevertheless, the scarcity of commercial Bi2Te3 raw materials has impeded the sustainable and widespread application of thermoelectric technology. In this study, we developed a low-cost and earth-abundant PbS compound with impressive thermoelectric performance. The optimized n-type PbS material achieved a record-high room temperature ZT of 0.64 in this system. Additionally, the first thermoelectric cooling device based on n-type PbS was fabricated, which exhibits a remarkable cooling temperature difference of ~36.9 K at room temperature. Meanwhile, the power generation efficiency of a single-leg device employing our n-type PbS material reaches ~8%, showing significant potential in harvesting waste heat into valuable electrical power. This study demonstrates the feasibility of sustainable n-type PbS as a viable alternative to commercial Bi2Te3, thereby extending the application of thermoelectrics.

16.
Int J Ophthalmol ; 17(5): 877-882, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766329

RESUMO

AIM: To investigate systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) levels in patients with type 2 diabetes at different stages of diabetic retinopathy (DR). METHODS: This retrospective study included 141 patients with type 2 diabetes mellitus (DM): 45 without diabetic retinopathy (NDR), 47 with non-proliferative diabetic retinopathy (NPDR), and 49 with proliferative diabetic retinopathy (PDR). Complete blood counts were obtained, and NLR, PLR, and SII were calculated. The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic (ROC) curves. The relationships between DR stages and SII, PLR, and NLP were assessed using multivariate logistic regression. RESULTS: The average NLR, PLR, and SII were higher in the PDR group than in the NPDR group (P=0.011, 0.043, 0.009, respectively); higher in the NPDR group than in the NDR group (P<0.001 for all); and higher in the PDR group than in the NDR group (P<0.001 for all). In the ROC curve analysis, the NLR, PLR, and SII were significant predictors of DR (P<0.001 for all). The highest area under the curve (AUC) was for the PLR (0.929 for PLR, 0.925 for SII, and 0.821 for NLR). Multivariate regression analysis indicated that NLR, PLR, and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM [odds ratio (OR)=1.122, 95% confidence interval (CI): 0.200-2.043, P<0.05; OR=0.038, 95%CI: 0.018-0.058, P<0.05; OR=0.007, 95%CI: 0.001-0.01, P<0.05, respectively). CONCLUSION: The NLR, PLR, and SII may be used as predictors of DR.

17.
Biomed Pharmacother ; 176: 116803, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788602

RESUMO

Exosomes, endogenous vesicles secreted by cells, possess unique properties like high biocompatibility, low immunogenicity, targeting ability, long half-life, and blood-brain barrier permeability. They serve as crucial intercellular communication vectors in physiological processes and disease occurrence. Our comprehensive analysis of exosome-based drug delivery research from 2013 to 2023 revealed 2,476 authors from 717 institutions across 33 countries. Keyword clustering identified five research areas: drug delivery, mesenchymal stem cells, cancer immunotherapy, targeting ligands, surface modifications, and macrophages. The combination of exosome drug delivery technology with a proven clinical model enables the precise targeting of tumors with chemotherapy or radiosensitising agents, as well as facilitating gene therapy. This bibliometric analysis aims to characterize the current state and advance the clinical application of exosome-based drug delivery systems.


Assuntos
Bibliometria , Sistemas de Liberação de Medicamentos , Exossomos , Exossomos/metabolismo , Humanos , Sistemas de Liberação de Medicamentos/métodos , Animais , Neoplasias/tratamento farmacológico , Neoplasias/patologia
18.
Sci Bull (Beijing) ; 69(11): 1728-1737, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38688741

RESUMO

Thermoelectric materials have a wide range of application because they can be directly used in refrigeration and power generation. And the Bi2Te3 stand out because of its excellent thermoelectric performance and are used in commercial thermoelectric devices. However, n-type Bi2Te3 has seriously hindered the development of Bi2Te3-based thermoelectric devices due to its weak mechanical properties and inferior thermoelectric performance. Therefore, it is urgent to develop a high-performance n-type Bi2Te3 polycrystalline. In this work, we employed interstitial Cu and the hot deformation process to optimize the thermoelectric properties of Bi2Te2.7Se0.3, and a high-performance thermoelectric module was fabricated based on this material. Our combined theoretical and experimental effort indicates that the interstitial Cu reduce the defect density in the matrix and suppresses the donor-like effect, leading to a lattice plainification effect in the material. In addition, the two-step hot deformation process significantly improves the preferred orientation of the material and boosts the mobility. As a result, a maximum ZT of 1.27 at 373 K and a remarkable high ZTave of 1.22 across the temperature range of 300-425 K are obtained. The thermoelectric generator (TEG, 7-pair) and thermoelectric cooling (TEC, 127-pair) modules were fabricated with our n-type textured Cu0.01Bi2Te2.7Se0.3 coupled with commercial p-type Bi2Te3. The TEC module demonstrates superior cooling efficiency compared with the commercial Bi2Te3 device, achieving a ΔT of 65 and 83.4 K when the hot end temperature at 300 and 350 K, respectively. In addition, the TEG module attains an impressive conversion efficiency of 6.5% at a ΔT of 225 K, which is almost the highest value among the reported Bi2Te3-based TEG modules.

19.
Am J Clin Nutr ; 119(4): 1027-1035, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38569774

RESUMO

BACKGROUND: The postoperative inflammatory response is associated with postoperative recovery in surgery. n-3 (ω-3) polyunsaturated fatty acids have been reported to lower inflammation. The postoperative role of parenteral n-3 polyunsaturated fatty acids supplementation on outcomes in Crohn's disease after bowel resection is unclear. OBJECTIVES: We aimed to investigate the effects of postoperative parenteral n-3 polyunsaturated fatty acids supplementation in Crohn's disease. METHODS: A prospective randomized, unblinded controlled clinical trial was conducted for patients with Crohn's disease who underwent bowel resection between May 2019 and February 2022. Postoperative complications, complete blood count, serum biochemical values, and cytokine concentrations were compared in patients with and without parenteral n-3 polyunsaturated fatty acids supplementation for 5 d postoperatively. RESULTS: There were 268 patients randomly assigned in the analysis, with 134 in the control group (a mix of long-chain and medium-chain fats at 1.0 g/kg/d) and 134 in the treatment group (long-chain, medium-chain, and n-3 polyunsaturated fats at 1.2 g/kg/d). Twenty-six did not complete the allocated treatment, and 8 patients were lost to follow-up. The intention-to-treat analysis and the per-protocol analysis showed that there were a significant reduction in overall complication rates (22.4% compared with 49.3%; P < 0.001 and 21.8% compared with 38.2%; P = 0.006) and postoperative stay (8.8 ± 4.5 d compared with 11.2 ± 6.8 d; P = 0.001 and 8.7 ± 4.0 d compared with 11.5 ± 7.3 d; P < 0.001) in patients with parenteral n-3 polyunsaturated fatty acids supplementation compared with patients in the control group. In the secondary outcomes, the mean ± standard deviation of interleukin (IL)-6 (17.11 ± 2.14 pg/mL compared with 30.50 ± 5.14 pg/mL; P = 0.014), IL-1ß (2.01 ± 0.05 pg/mL compared with 2.24 ± 0.09 pg/mL; P = 0.019), tumor necrosis factor-α (2.09 ± 0.06 pg/mL compared with 2.29 ± 0.06 pg/mL; P = 0.029), and C-reactive protein concentrations (51.3 ± 4.2 mg/L compared with 64.4 ± 5.3 mg/L; P = 0.050) on postoperative day 5 in the treatment group were much lower than those in the control group. CONCLUSIONS: Parenteral n-3 polyunsaturated fatty acids supplementation promotes postoperative recovery in patients with Crohn's disease following bowel resection, with fewer complications and reduced inflammatory cytokines. This trial was registered at clinicaltrials.gov as NCT03901937 at https://classic. CLINICALTRIALS: gov/ct2/show/NCT03901937?term=NCT03901937&cond=Crohn+Disease&draw=2&rank=1.


Assuntos
Doença de Crohn , Ácidos Graxos Ômega-3 , Humanos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Estudos Prospectivos , Ácidos Graxos Ômega-3/uso terapêutico , Nutrição Parenteral , Citocinas , Interleucina-6 , Suplementos Nutricionais
20.
Front Pharmacol ; 15: 1371574, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576492

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, resulting in a huge medical burden worldwide. Accumulating evidence suggests that the gut microbiome and bile acids play pivotal roles during the development of NAFLD. Patients with NAFLD exhibit unique signatures of the intestinal microbiome marked by the priority of Gram-negative bacteria, decreased ratio of Firmicutes/Bacteroidetes (F/B), and increased Prevotella and Lachnospiraceae. The intestinal microbiota is involved in the metabolism of bile acids. Ursodeoxycholic acid (UDCA) is a key determinant in maintaining the dynamic communication between the host and gut microbiota. It generally shows surprising therapeutic potential in NAFLD with several mechanisms, such as improving cellular autophagy, apoptosis, and mitochondrial functions. This action is based on its direct or indirect effect, targeting the farnesoid X receptor (FXR) and various other nuclear receptors. This review aims to discuss the current studies on the involvement of the microbiome-UDCA interface in NAFLD therapy and provide prospective insights into future preventative and therapeutic approaches for NAFLD.

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