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1.
J Geriatr Cardiol ; 21(5): 523-533, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38948897

RESUMO

OBJECTIVES: To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS: We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542-5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041-6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS: This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI.

2.
PLoS Biol ; 22(5): e3002619, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38814985

RESUMO

The CRISPR-associated endonuclease Cas12a has become a powerful genome-editing tool in biomedical research due to its ease of use and low off-targeting. However, the size of Cas12a severely limits clinical applications such as adeno-associated virus (AAV)-based gene therapy. Here, we characterized a novel compact Cas12a ortholog, termed EbCas12a, from the metagenome-assembled genome of a currently unclassified Erysipelotrichia. It has the PAM sequence of 5'-TTTV-3' (V = A, G, C) and the smallest size of approximately 3.47 kb among the Cas12a orthologs reported so far. In addition, enhanced EbCas12a (enEbCas12a) was also designed to have comparable editing efficiency with higher specificity to AsCas12a and LbCas12a in mammalian cells at multiple target sites. Based on the compact enEbCas12a, an all-in-one AAV delivery system with crRNA for Cas12a was developed for both in vitro and in vivo applications. Overall, the novel smallest high-fidelity enEbCas12a, this first case of the all-in-one AAV delivery for Cas12a could greatly boost future gene therapy and scientific research.


Assuntos
Sistemas CRISPR-Cas , Dependovirus , Edição de Genes , Vetores Genéticos , Dependovirus/genética , Humanos , Edição de Genes/métodos , Vetores Genéticos/genética , Animais , Células HEK293 , Terapia Genética/métodos , Proteínas Associadas a CRISPR/metabolismo , Proteínas Associadas a CRISPR/genética , Camundongos , Endodesoxirribonucleases/metabolismo , Endodesoxirribonucleases/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
3.
Materials (Basel) ; 17(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38473638

RESUMO

The differences in geomechanical properties and the uncertainty in the spatial distribution of Bimrock pose significant challenges to the construction and disaster prediction of geotechnical engineering. To clarify the geomechanical characteristics of Bimrock, this paper summarizes the basic concepts and classification methods of Bimrock at home and abroad. It discusses the methods and characteristics of determining the geometric features of Bimrock blocks and explores the influencing factors and laws of failure modes and strength under different stress states of Bimrock. The study finds that the failure mode of Bimrock is mainly influenced by factors such as block proportion, degree of welding between blocks and matrix, strength ratio between blocks and matrix, and geometric properties of blocks. Among these factors, block proportion is the most significant, and the degree of welding is a controlling factor. However, due to the complexity of Bimrock structures, there is a lack of applicable methods and mechanical models for the evaluation of geomechanical characteristics of Bimrock in engineering practice. This article also explores the influence and research methods of the geological characteristics of Bimrock in slope and tunnel engineering and, finally, provides prospects for the future research trends relating to Bimrock.

4.
Small ; : e2401172, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552220

RESUMO

Fabricating covalent organic framework (COF) membranes through the pre-assembly of nanosheets with different properties may open a novel avenue to the fabrication of advanced 2D membranes. Herein, COF membranes are fabricated using oppositely-charged COF nanosheets (CONs). Negatively-charged CONs and positively-charged CONs are pre-assembled through simple physical mixing, yielding the CONs with an aspect ratio of exceeding 10 000, which are assembled into three kinds of COF membranes. The optimal membranes exhibit the highest desalination performance with permeation flux of 132.66 kg m-2 h-1, salt rejection of 99.99%, and superior long-term operation stability.

5.
PLoS Biol ; 22(3): e3002514, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483978

RESUMO

The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a system is a powerful tool in gene editing; however, crRNA-DNA mismatches might induce unwanted cleavage events, especially at the distal end of the PAM. To minimize this limitation, we engineered a hyper fidelity AsCas12a variant carrying the mutations S186A/R301A/T315A/Q1014A/K414A (termed HyperFi-As) by modifying amino acid residues interacting with the target DNA and crRNA strand. HyperFi-As retains on-target activities comparable to wild-type AsCas12a (AsCas12aWT) in human cells. We demonstrated that HyperFi-As has dramatically reduced off-target effects in human cells, and HyperFi-As possessed notably a lower tolerance to mismatch at the position of the PAM-distal region compared with the wild type. Further, a modified single-molecule DNA unzipping assay at proper constant force was applied to evaluate the stability and transient stages of the CRISPR/Cas ribonucleoprotein (RNP) complex. Multiple states were sensitively detected during the disassembly of the DNA-Cas12a-crRNA complexes. On off-target DNA substrates, the HyperFi-As-crRNA was harder to maintain the R-loop complex state compared to the AsCas12aWT, which could explain exactly why the HyperFi-As has low off-targeting effects in human cells. Our findings provide a novel version of AsCas12a variant with low off-target effects, especially capable of dealing with the high off-targeting in the distal region from the PAM. An insight into how the AsCas12a variant behaves at off-target sites was also revealed at the single-molecule level and the unzipping assay to evaluate multiple states of CRISPR/Cas RNP complexes might be greatly helpful for a deep understanding of how CRISPR/Cas behaves and how to engineer it in future.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Humanos , Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas , Endonucleases/genética , Endonucleases/metabolismo , DNA/genética
6.
BMJ Open ; 14(1): e078092, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38199635

RESUMO

INTRODUCTION: Postoperative pancreatic fistula (POPF) remains one of the most severe complications of laparoscopic pancreaticoduodenectomy (LPD). Theoretically, transecting the pancreatic neck more distally has both advantages (more blood supply, and more central pancreatic duct) and disadvantages (maybe smaller the pancreatic duct) in preventing POPF. This theoretical contradiction pushed us to organise this trial to explore the impact of the level of pancreatic transection in clinical practice. We conduct this randomised trial with the hypothesis that extended pancreatic neck transection has superiority to conventional pancreatic neck transection. METHODS AND ANALYSIS: The LPDEXCEPT (Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy) trial is a multicentre, randomised-controlled, open-label, superiority trial in 4 centres whose annual surgical volume for LPD is more than 25 cases with pancreatic surgeons who had completed their learning curve. A total of 154 patients who meet the inclusive and exclusive criteria are randomly allocated to the extended pancreatic neck transection group or conventional pancreatic neck transection group in a 1:1 ratio. The stratified randomised block design will be applied, with stratified factors are surgical centre and the diameter of the main pancreatic duct measured by preoperative CT scan (preMPD). The primary outcome is the incidence of the clinically relevant pancreatic fistula. ETHICS AND DISSEMINATION: Ethics Committee on Biomedical Research of West China Hospital of Sichuan University has approved this trial in March 2023 (approval no. 2023-167). Results of this trial will be published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: NCT05808894.


Assuntos
Laparoscopia , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/efeitos adversos , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Pâncreas , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
7.
Cardiol J ; 31(1): 32-44, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37853822

RESUMO

BACKGROUND: Lipoprotein(a) [Lp(a)] was positively associated with recurrent ischemic events in patients with acute coronary syndrome (ACS). This study was performed to investigate the effect of Lp(a) levels on outcomes of dual antiplatelet therapy (DAPT) > 1 year versus DAPT ≤ 1 year after percutaneous coronary intervention (PCI) in this population. METHODS: A total of 4,357 ACS patients who were event-free at 1 year after PCI were selected from the Fuwai PCI Registry, and patients were stratified into four groups according to DAPT duration (≤ 1 year vs. > 1 year) and Lp(a) levels (≤ 30 mg/dL vs. > 30 mg/dL). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of cardiac death, myocardial infarction or stroke. RESULTS: After 2.4-year follow-up, the incidence of MACCE (HRadjusted 0.284, 95% CI 0.115-0.700; HRIPTW 0.351, 95% CI 0.164-0.751) were significantly reduced in DAPT > 1 year group than that in DAPT ≤ 1 year group in individuals with elevated Lp(a) levels. However, in individuals with normal Lp(a) levels, no statistically difference was found between these two groups in terms of MACCE, although the risks of all-cause death and definite/probable stent thrombosis were lower in DAPT > 1 year group. Notably, the risk of clinically relevant bleeding did not statistically differ between these two groups in individuals with different Lp(a) levels. CONCLUSIONS: This study firstly demonstrated that extended DAPT (> 1 year) was statistically associated with lower risk of ischemic events in ACS patients with elevated Lp(a) levels after PCI, whereas this association was not found in individuals with normal Lp(a) levels.


Assuntos
Síndrome Coronariana Aguda , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Intervenção Coronária Percutânea/efeitos adversos , Lipoproteína(a) , Quimioterapia Combinada , Resultado do Tratamento
8.
BMC Public Health ; 23(1): 2463, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066518

RESUMO

BACKGROUND: A major shift in the "dynamic zero-COVID" policy was announced by China's National Health Commission on December 7, 2022, and the subsequent immediate large-scale outbreak of SARS-CoV-2 infections in the entire country has caused worldwide concern. This observational cross-sectional study aimed to describe the epidemiological characteristics of this outbreak in Sichuan, China. METHODS: All data were self-reported online by volunteers. We described the epidemic by characterizing the infection, symptoms, clinical duration, severity, spatiotemporal clustering, and dynamic features of the disease. Prevalence ratio (PR), Odds ratios (ORs) and adjusted ORs were calculated to analyze the associations between risk factors and infection and the associations of risk factors with clinical severity using log-binomial and multivariable logistic regression models; 95% confidence intervals (CIs) and Wald test results were reported. The prevalence rates and clinical severity among different subgroups were compared using the Chi-square and trend Chi-square tests. RESULTS: Between January 6 and 12, 2023, 138,073 volunteers were enrolled in this survey, and 102,645 were infected with COVID-19, holding a prevalence rate of 74.34%; the proportion of asymptomatic infections was 1.58%. Log-binomial regression revealed that the risk of infection increased among those living in urban areas. Multivariable logistic regression analysis showed that female sex, chronic diseases, older age and the fewer doses of vaccine received were associated with an increased risk of severe clinical outcomes after infection. We estimated the mean reproduction number during this pandemic was 1.83. The highest time-dependent reproduction number was 4.15; this number decreased below 1 after 11 days from December 7, 2022. Temporal trends revealed a single peak curve with a plateau pattern of incidence during the outbreak, whereas spatiotemporal clustering analysis showed that the onset in 21 cities in the Sichuan province had four-wave peaks. CONCLUSIONS: The peak of the first wave of Omicron infection in Sichuan Province had passed and could be considered a snapshot of China under the new control strategy. There were significant increases in the risk of severe clinical outcomes after infection among females, with chronic diseases, and the elderly. The vaccines have been effective in reducing poor clinical outcomes.


Assuntos
COVID-19 , Idoso , Feminino , Humanos , China/epidemiologia , Doença Crônica , COVID-19/epidemiologia , Estudos Transversais , Surtos de Doenças/prevenção & controle , SARS-CoV-2 , Inquéritos e Questionários , Masculino
9.
Clin Cancer Res ; 29(23): 4740-4750, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37801296

RESUMO

PURPOSE: Fibroblast activation protein (FAP) is a promising target for tumor treatment. In this study, we aimed to investigate the safety and efficacy of the albumin binder-conjugated FAP-targeted radiopharmaceutical, 177Lu-EB-FAPI (177Lu-LNC1004), in patients with metastatic radioiodine-refractory thyroid cancer (mRAIR-TC). PATIENTS AND METHODS: This open-label, non-randomized, first-in-human, dose-escalation, investigator-initiated trial had a 3+3 design and involved a 6-week 177Lu-LNC1004 treatment cycle in patients with mRAIR-TC at 2.22 GBq initially, with subsequent cohorts receiving an incremental 50% dose increase until dose-limiting toxicity (DLT) was observed. RESULTS: 177Lu-LNC1004 administration was well tolerated, with no life-threatening adverse events observed. No patients experienced DLT in Group A (2.22 GBq/cycle). One patient experienced grade 4 thrombocytopenia in Group B (3.33 GBq/cycle); hence, another three patients were enrolled, none of whom experienced DLT. Two patients experienced grade 3 and 4 hematotoxicity in Group C (4.99 GBq/cycle). The mean whole-body effective dose was 0.17 ± 0.04 mSv/MBq. Intense 177Lu-LNC1004 uptake and prolonged tumor retention resulted in high mean absorbed tumor doses (8.50 ± 12.36 Gy/GBq). The mean effective half-lives for the whole-body and tumor lesions were 90.20 ± 7.68 and 92.46 ± 9.66 hours, respectively. According to RECIST, partial response, stable disease, and progressive disease were observed in 3 (25%), 7 (58%), and 2 (17%) patients, respectively. The objective response and disease control rates were 25% and 83%, respectively. CONCLUSIONS: FAP-targeted radioligand therapy with 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated in patients with advanced mRAIR-TC, with high radiation dose delivery to the tumor lesions, encouraging therapeutic efficacy, and acceptable side effects.


Assuntos
Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Masculino , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Compostos Radiofarmacêuticos/efeitos adversos , Antígeno Prostático Específico , Fibroblastos
10.
J Am Heart Assoc ; 12(20): e030625, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37804199

RESUMO

Background Serum uric acid (UA) is correlated closely with traditional cardiovascular risk factors, which might interfere with the action of UA, in patients with coronary artery disease. We performed this study to evaluate the prognostic effect of UA levels in individuals with different numbers of standard modifiable cardiovascular risk factors (SMuRFs). Methods and Results In this prospective study, we consecutively enrolled 10 486 patients with coronary artery disease. They were stratified into 3 groups according to the tertiles of UA concentrations and, within each UA tertile, further classified into 3 groups by the number of SMuRFs (0-1 versus 2-3 versus 4). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and unplanned revascularization. Over a median follow-up of 2.4 years, 1233 (11.8%) MACCEs were recorded. Patients with high UA levels developed significantly higher risk of MACCEs than those with low UA levels. In addition, UA levels were positively associated with MACCEs as a continuous variable. More importantly, in patients with 0 to 1 SMuRF, the risks of MACCEs were significantly higher in the high-UA-level group (adjusted hazard ratio [HR], 1.469 [95% CI, 1.197-1.804]) and medium-UA-level group (adjusted HR, 1.478 [95% CI, 1.012-2.160]), compared with the low-UA-level group, whereas no significant association was found between UA levels and the risk of MACCEs in participants with 2 to 3 or 4 SMuRFs. Conclusions In patients with coronary artery disease who received evidence-based secondary prevention therapies, elevated UA levels might affect the prognosis of individuals with 0 to 1 SMuRF but not that of individuals with ≥2 SMuRFs.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Estudos de Coortes , Ácido Úrico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Fatores de Risco , Prognóstico , Fatores de Risco de Doenças Cardíacas , Ásia
11.
Appl Opt ; 62(29): 7721-7729, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37855480

RESUMO

Due to the huge demand for higher resolution and stable imaging from fluorescent labeling biological systems and life systems, there has been much research and development of structured light illumination imaging (SIM). Despite this, further investigating the possible applications of SIM in other fields is still meaningful. In this paper, super-resolution observation of non-fluorescent samples by a SIM system under reflective illumination is analyzed. The simulation of SIM imaging and image reconstruction is carried out by using an open-source program, and the influences of the structural parameters of the illumination light (fringe direction, phase, and intensity uniformity of the cosine structured light), the optical parameters of the imaging system (selection of the optical transfer function) and the anti-vibration characteristics of the platform on the super-resolution imaging effect are studied. Finally, by optimizing the above influential factors according to simulation results, successful application of SIM in laser processing process monitoring is demonstrated in the experiment. We believe that our research results will provide some reference for the application of SIM in other similar scenarios.

12.
Angew Chem Int Ed Engl ; 62(42): e202310238, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37665568

RESUMO

Photosynthesis offers a green approach for the recycling of nicotinamide cofactors primarily NADH in bio-redox reactions. Herein, we report an NADH photosynthesis system where the oxidation of biomass derivatives is designed as an electron supply module (ESM) to afford electrons and superoxide dismutase/catalase (SOD/CAT) cascade catalysis is designed as a reactive oxygen species (ROS) elimination module (REM) to inhibit NADH degradation. Glucose as the electron donor guarantees the reaction sustainability accompanied with oxidative products of gluconic acid and formic acid. Meanwhile, enzyme cascades of SOD/CAT greatly eliminate ROS, leading to a ≈2.00-fold elevation of NADH yield (61.1 % vs. 30.7 %). The initial reaction rate and turnover frequency (TOF) increased by 2.50 times and 2.54 times, respectively, compared with those systems without REM. Our study establishes a novel and efficient platform for NADH photosynthesis coupled to biomass-to-chemical conversion.

13.
J Cancer ; 14(12): 2209-2223, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576389

RESUMO

Background: Hepatocellular carcinoma (HCC) has limited prognostic prediction due to its heterogeneity. Understanding the role of natural killer (NK) cells in HCC is vital for prognosis and immunotherapy guidance. We aimed to identify NK cell marker genes through scRNA-seq and develop a prognostic signature for HCC. Methods: We analyzed scRNA-seq data (GSE149614) from 10 patients and bulk RNA-seq data from 786 patients with clinicopathological information. NK cell marker genes were identified using clustering and marker finding functions. A predictive risk signature was constructed using LASSO-COX algorithm. Functional annotations and immune cell infiltration analysis were performed, and the nomogram's performance was evaluated. Results: We identified 79 NK cell marker genes associated with NK cell-mediated cytotoxicity, apoptosis, and immune response. The multigene signature significantly correlated with overall survival (OS) in TCGA-LIHC cohort and was validated in other cohorts. Low-risk patients exhibited higher immune cell infiltration, including CD8+ T cells. The risk signature was an independent prognostic factor for OS (HR > 1, p < 0.001). The nomogram combining the risk signature and clinical predictors demonstrated robust prognostic ability. Conclusion: We developed a nine-gene signature prognostic model based on NK cell marker genes to accurately assess the prognostic risk of HCC. This model can be a valuable tool for personalized evaluation post-surgery. Our study underscores the potential of NK cells in HCC prognosis and highlights the importance of scRNA-seq analysis in identifying prognostic markers.

14.
Cardiovasc Diabetol ; 22(1): 165, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37403082

RESUMO

BACKGROUND: Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes. METHODS: In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5,308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/l))/(1.59×HbA1c (%)-2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7% vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014-8.228) and nondiabetic cohort (8.8% vs. 2.2%; adjusted OR 2.976, 95% CI 1.695-5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status. CONCLUSIONS: This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT01874691.


Assuntos
Diabetes Mellitus , Hiperglicemia , Infarto do Miocárdio , Humanos , Hemoglobinas Glicadas , Glicemia/metabolismo , Mortalidade Hospitalar , Estudos Prospectivos , Diabetes Mellitus/epidemiologia , China/epidemiologia , Jejum , Sistema de Registros
15.
Int Immunopharmacol ; 121: 110350, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37290325

RESUMO

The use of aspirin is associated with reduced incidence of colorectal cancer (CRC). However, the detailed mechanism remains unclear. In this study, we reported that colon cancer cells treated with aspirin showed the hallmarks of immunogenic cell death (ICD), including surface expression of calreticulin (CRT) and heat shock protein 70 (HSP70). Mechanistically, aspirin induced endoplasmic reticulum (ER) stress in colon cancer cells. In addition, aspirin decreased the expression of the glucose transporters, GLUT3, and reduced the key enzyme of glycolysis, including HK2, PFKM, PKM2 and LDHA. The changes of tumor glycolysis after aspirin treatment were associated with c-MYC downregulation. Moreover, aspirin potentiated the antitumor efficacy of anti-PD-1 antibody and anti-CTLA-4 antibody in CT26 tumors. However, this antitumor activity of aspirin in combination with anti-PD-1 antibody was abolished by the depletion of CD8+ T cells. Vaccination with tumor antigens is one of the strategies for activating T-cell response against tumors. Here, we demonstrated that aspirin-treated tumor cells in combination with tumor antigens (AH1 peptide) or protective substituted peptide (A5 peptide) could be served as a potent vaccine to eradicate tumors. Overall, our data indicated that aspirin can be used as an inducer of ICD for CRC therapy.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias do Colo , Humanos , Linhagem Celular Tumoral , Morte Celular Imunogênica , Antígenos de Neoplasias , Imunoterapia
16.
Cell Insight ; 2(1): 100076, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37192909

RESUMO

Evidence shows that some class I human leucocyte antigen (HLA) alleles are related to durable HIV controls. The T18A TCR, which has the alloreactivity between HLA-B∗42:01 and HLA-B∗81:01 and the cross-reactivity with different antigen mutants, can sustain long-term HIV controls. Here the structural basis of the T18A TCR binding to the immunodominant HIV epitope TL9 (TPQDLNTML180-188) presented by HLA-B∗42:01 was determined and compared to T18A TCR binding to the TL9 presented by the allo-HLA-B∗81:01. For differences between HLA-B∗42:01 and HLA-B∗81:01, the CDR1α and CDR3α loops adopt a small rearrangement to accommodate them. For different conformations of the TL9 presented by different HLA alleles, not like the conventional recognition of CDR3s to interact with peptide antigens, CDR3ß of the T18A TCR shifts to avoid the peptide antigen but intensively recognizes the HLA only, which is different with other conventional TCR structures. Featured sequence pairs of CDR3ß and HLA might account for this and were additionally found in multiple other diseases indicating the popularity of the unconventional recognition pattern which would give insights into the control of diseases with epitope mutating such as HIV.

17.
J Geriatr Cardiol ; 20(3): 185-194, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37091264

RESUMO

OBJECTIVES: To assess the correlation between triglyceride glucose (TyG) index and in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 2190 patients with STEMI who underwent primary angiography within 12 h from symptom onset were selected from the prospective, nationwide, multicenter CAMI registry. TyG index was calculated with the formula: Ln [fasting triglycerides (mmol/L) × fasting glucose (mmol/L)/2]. Patients were divided into three groups according to the tertiles of TyG index. The primary endpoint was in-hospital mortality. RESULTS: Overall, 46 patients died during hospitalization, in-hospital mortality was 1.5%, 2.2%, 2.6% for tertile 1, tertile 2, and tertile 3, respectively. However, TyG index was not significantly correlated with in-hospital mortality in single-variable logistic regression analysis. Nonetheless, after adjusting for age and sex, TyG index was significantly associated with higher mortality when regarded as a continuous variable (adjusted OR = 1.75, 95% CI: 1.16-2.63) or categorical variable (tertile 3 vs. tertile 1: adjusted OR = 2.50, 95% CI: 1.14-5.49). Furthermore, TyG index, either as a continuous variable (adjusted OR = 2.54, 95% CI: 1.42-4.54) or categorical variable (tertile 3 vs. tertile 1: adjusted OR = 3.57, 95% CI: 1.24-10.29), was an independent predictor of in-hospital mortality after adjusting for multiple confounders in multivariable logistic regression analysis. In subgroup analysis, the prognostic effect of high TyG index was more significant in patients with body mass index < 18.5 kg/m2 (P interaction = 0.006). CONCLUSIONS: This study showed that TyG index was positively correlated with in-hospital mortality in STEMI patients who underwent primary angiography, especially in underweight patients.

18.
Nutr Diabetes ; 13(1): 5, 2023 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-37076479

RESUMO

BACKGROUND: Dietary management plays an important role in diabetes care, while the trends in dietary patterns over the last decade in US adults with diagnosed and undiagnosed diabetes remain unknown. This study aims to estimate the dietary patterns over the last decade by baseline diabetes diagnoses and explore their association with long-term prognosis. METHODS: Participants' data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2007-2018, which were divided into three groups according to the diabetes diagnosis: without diabetes, undiagnosed diabetes, and diagnosed diabetes. Healthy eating index (HEI) and dietary inflammatory index (DII) were used to evaluate dietary patterns. Survival analyses were adopted to estimate the association between HEI/DII scores and long-term all-cause mortality and cause-specific mortality. RESULTS: The prevalence of diabetes was increasing among US adults over the last decade. HEI scores of all three groups presented a downward trend in recent years. Participants with undiagnosed diabetes (weighted mean: 50.58, 95% CI: 49.79, 51.36) got significantly lower HEI score in comparison to participants with diagnosed diabetes (weighted mean: 51.59, 95% CI: 50.93, 52.25). Compared with participants without diabetes, participants in the undiagnosed or diagnosed diabetes group had higher DII scores, indicating a higher dietary inflammatory potential. Survival analysis found a significant association between HEI scores and all-cause mortality and death of heart diseases. Similar correlation was observed in DII scores. CONCLUSIONS: Along with the growth in diabetes prevalence in the US, dietary management of people with diabetes is decreasing. The management of US adults' diets needs special attention, and dietary inflammatory potential may be considered in the dietary intervention.


Assuntos
Diabetes Mellitus , Dieta , Adulto , Humanos , Inquéritos Nutricionais , Dieta Saudável , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia
19.
J Biomater Appl ; 37(9): 1676-1686, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36879543

RESUMO

The metal gallium holds great promise in the fight against infection by disrupting bacterial iron metabolism through a "Trojan horse" technique. It is well worth trying to investigate the potential for gallium-mediated hydrogels for the treatment of infected wounds. In this paper, Ga3+ is innovatively given an important role in hydrogels based on the conventional multi-component hydrogel with metal ion binding gelation strategy. Thus, Ga@Gel-Alg-CMCs hydrogel with broad-spectrum antimicrobial activity is reported on the treatment of infected wounds. The morphology, degradability, and swelling behavior together indicated the excellent physical properties of this hydrogel. Interestingly, in vivo results also showed favorable biocompatibility, slowing down wound infection and promoting diabetic wound healing, making the gallium-doped hydrogel an ideal antimicrobial dressing.


Assuntos
Anti-Infecciosos , Diabetes Mellitus , Humanos , Hidrogéis/química , Cicatrização , Bandagens , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química
20.
Eur J Prev Cardiol ; 30(14): 1418-1426, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36987575

RESUMO

AIMS: To evaluate the impact of prediabetes identified by different glycemic thresholds (according to ADA or WHO/IEC criteria) and diagnostic tests (fasting plasma glucose [FPG] or hemoglobin A1c [HbA1c]) on clinical outcomes in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: In this prospective cohort study, we consecutively enrolled 4088 stable CAD non-diabetic patients with a median follow-up period of 3.2 years. Prediabetes was defined according to ADA criteria as FPG 5.6∼6.9 mmol/L and/or HbA1c 5.7∼6.4%, and WHO/IEC criteria as FPG 6.1∼6.9 mmol/L and/or HbA1c 6.0∼6.4%. The primary endpoint was major adverse cardiovascular event (MACE), including all-cause death, myocardial infarction, or stroke. The prevalence of prediabetes defined according to ADA criteria (67%) was double that of WHO/IEC criteria (34%). Compared with patients with normoglycaemia, those with WHO/IEC-defined prediabetes were significantly associated with higher risk of MACE [adjusted hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.10-2.06], mainly driven by the higher incidence of events in individuals with HbA1c-defined prediabetes. However, this difference was not found in patients with ADA-defined prediabetes and normoglycaemia (adjusted HR 1.17, 95% CI 0.81-1.68). Although FPG was not associated with cardiovascular events, HbA1c improved the risk prediction for MACE in a model of traditional risk factors. Furthermore, the optimal cutoff value of HbA1c for predicting MACE was 5.85%, which was close to the threshold recommended by IEC. CONCLUSION: This study supports the use of WHO/IEC criteria for the identification of prediabetes in stable CAD patients. Haemoglobin A1c, rather than FPG, should be considered as a useful marker for risk stratification in this population. REGISTRATION: Not applicable.


This study, for the first time, evaluated the prognostic effect of prediabetes identified by different glycaemic thresholds (ADA or WHO/IEC criteria) and diagnostic tests (FPG or HbA1c) in individuals with stable CAD. The results of this study support the identification of individuals with prediabetes using WHO/IEC criteria in stable, angiography-proven CAD patients. Haemoglobin A1c, rather than FPG, should be considered as a useful marker for risk stratification and the optimal cutoff value of HbA1c for predicting MACE was 5.85%, which was close to the threshold of 6.0% recommended by IEC.


Assuntos
Doença da Artéria Coronariana , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Prognóstico , Hemoglobinas Glicadas , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/complicações , Glicemia , Estudos Prospectivos , Fatores de Risco , Ásia
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