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1.
Cardiovasc Diabetol ; 23(1): 270, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044255

RESUMO

BACKGROUND: A significant percentage of patients with acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) are being identified. Nonetheless, the prognostic influence of the TyG index on adverse events in this type of patient remains unexplored. The aim of this study was to assess the prognostic value of the TyG index among ACS patients without SMuRFs for predicting adverse outcomes. METHODS: This study involved 1140 consecutive patients who were diagnosed with ACS without SMuRFs at Beijing Anzhen Hospital between May 2018 and December 2020 and underwent coronary angiography. Each patient was followed up for a period of 35 to 66 months after discharge. The objective of this study was to examine major adverse cardiac and cerebrovascular events (MACCE), which included all-cause mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, as well as ischemia-driven revascularization. RESULTS: During the median follow-up period of 48.3 months, 220 (19.3%) MACCE events occurred. The average age of the participants was 59.55 ± 10.98 years, and the average TyG index was 8.67 ± 0.53. In the fully adjusted model, when considering the TyG index as either a continuous/categorical variable, significant associations with adverse outcomes were observed. Specifically, for each 1 standard deviation increase in the TyG index within the highest TyG index group, there was a hazard ratio (HR) of 1.245 (95% confidence interval CI 1.030, 1.504) for MACCE and 1.303 (95% CI 1.026, 1.653) for ischemia-driven revascularization (both P < 0.05), when the TyG index was analyzed as a continuous variable. Similarly, when the TyG index was examined as a categorical variable, the HR (95% CI) for MACCE in the highest TyG index group was 1.693 (95% CI 1.051, 2.727) (P < 0.05) in the fully adjusted model, while the HR (95% CI) for ischemia-driven revascularization was 1.855 (95% CI 0.998, 3.449) (P = 0.051). Additionally, the TyG index was found to be associated with a poor prognosis among the subgroup. CONCLUSION: The TyG index is correlated with poor prognosis in patients with ACS without SMuRFs, suggesting that it may be an independent predictive factor of adverse events among these individuals.


Assuntos
Síndrome Coronariana Aguda , Biomarcadores , Glicemia , Valor Preditivo dos Testes , Triglicerídeos , Humanos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Medição de Risco , Prognóstico , Biomarcadores/sangue , Triglicerídeos/sangue , Fatores de Tempo , Pequim/epidemiologia , Glicemia/metabolismo , Fatores de Risco de Doenças Cardíacas , Estudos Retrospectivos , Angiografia Coronária
2.
Cardiovasc Diabetol ; 23(1): 267, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039597

RESUMO

BACKGROUND: Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) is a novel oral drug for treating type 2 diabetes mellitus (T2DM) with demonstrated cardiovascular benefits. Previous studies in apolipoprotein E knockout mice have shown that SGLT2i is associated with attenuated progression of atherosclerosis. However, whether this effect extends to T2DM patients with coronary atherosclerosis in real-world settings remains unknown. METHODS: In this longitudinal cohort study using coronary computed tomography angiography (CCTA), T2DM patients who underwent ≥ 2 CCTA examinations at our center between 2019 and 2022 were screened. Eligible patients had multiple study plaques, defined as non-obstructive stenosis at baseline and not intervened during serial CCTAs. Exclusion criteria included a CCTA time interval < 12 months, prior SGLT2i treatment, or initiation/discontinuation of SGLT2i during serial CCTAs. Plaque volume (PV) and percent atheroma volume (PAV) were measured for each study plaque using CCTA plaque analysis software. Patients and plaques were categorized based on SGLT2i therapy and compared using a 1:1 propensity score matching (PSM) analysis. RESULTS: The study included 236 patients (mean age 60.5 ± 9.5 years; 69.1% male) with 435 study plaques (diameter stenosis ≥ 50%, 31.7%). Following SGLT2i treatment for a median duration of 14.6 (interquartile range: 13.0, 20.0) months, overall, non-calcified, and low-attenuation PV and PAV were significantly decreased, while calcified PV and PAV were increased (all p < 0.001). Meanwhile, reductions in overall PV, non-calcified PV, overall PAV, and non-calcified PAV were significantly greater in SGLT2i-treated compared to non-SGLT2i-treated plaques (all p < 0.001). PSM analysis showed that SGLT2i treatment was associated with higher reductions in overall PV (- 11.77 mm3 vs. 4.33 mm3, p = 0.005), non-calcified PV (- 16.96 mm3 vs. - 1.81 mm3, p = 0.017), overall PAV (- 2.83% vs. 3.36%, p < 0.001), and non-calcified PAV (- 4.60% vs. 0.70%, p = 0.003). These findings remained consistent when assessing annual changes in overall and compositional PV and PAV. Multivariate regression models demonstrated that SGLT2i therapy was associated with attenuated progression of overall or non-calcified PV or PAV, even after adjusting for cardiovascular risk factors, medications, and baseline overall or non-calcified PV or PAV, respectively (all p < 0.05). The effect of SGLT2i on attenuating non-calcified plaque progression was consistent across subgroups (all p for interaction > 0.05). CONCLUSIONS: In this longitudinal CCTA cohort of T2DM patients, SGLT2i therapy markedly regressed coronary overall PV and PAV, mainly result from a significant reduction in non-calcified plaque.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Placa Aterosclerótica , Valor Preditivo dos Testes , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Feminino , Pessoa de Meia-Idade , Estudos Longitudinais , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Idoso , Resultado do Tratamento , Fatores de Tempo , Estudos Retrospectivos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos
3.
Opt Lett ; 49(12): 3320-3323, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38875610

RESUMO

During data transmission, the dynamic change of a scattering medium will make the measured transmission matrix (TM) invalid, so it is necessary to repeatedly measure the TM to achieve a long-time data transmission, which requires stopping the data transmission process frequently to measure the TM and leads to a reduction in the communication capacity. To solve this problem, we propose a TM tracking method during data transmission. In the case of more than three discrete levels of phase modulation, this method can realize the calibration of the TM with the intensity pictures captured by the camera and the recovered data, so it does not require stopping the data transmission process to measure the TM and thus avoids the loss of communication capacity. We have proved the feasibility of this method through simulations and experiments and realized the continuous transmission of random data and image data through a moving fiber with high accuracy.

4.
J Magn Reson Imaging ; 59(4): 1327-1340, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37403942

RESUMO

BACKGROUND: Brain MRI scanner variability can introduce bias in measurements. Harmonizing scanner variability is crucial. PURPOSE: To develop a harmonization method aimed at removing scanner variability, and to evaluate the consistency of results in multicenter studies. STUDY TYPE: Retrospective. POPULATION: Multicenter data from 170 healthy participants (males/females = 98/72; age = 73.8 ± 7.3) and 170 Alzheimer's disease patients (males/females = 98/72; age = 76.2 ± 8.5) were compared with reference data from another 340 participants. FIELD STRENGTH/SEQUENCE: 3-T, magnetization prepared rapid gradient echo and turbo field echo; 1.5-T, inversion recovery prepared fast spoiled gradient echo T1-weighted sequences. ASSESSMENT: Gray matter (GM) brain images, obtained through segmentation of T1-weighted images, were utilized to evaluate the performance of the harmonization method using common orthogonal basis extraction (HCOBE) and four other methods (removal of artificial voxel effect by linear regression, RAVEL; Z_score; general linear model, GLM; ComBat). Linear discriminant analysis (LDA) was used to access the effectiveness of different methods in reducing scanner variability. The performance of harmonization methods in preserving GM volumes heterogeneity was evaluated by the similarity of the relationship between GM proportion and age in the reference and multicenter data. Furthermore, the consistency of the harmonized multicenter data with the reference data were evaluated based on classification results (train/test = 7/3) and brain atrophy. STATISTICAL TESTS: Two-sample t-tests, area under the curve (AUC), and Dice coefficients were used to analyze the consistency of results from the reference and harmonized multicenter data. A P-value <0.01 was considered statistically significant. RESULTS: HCOBE reduced the scanner variability from 0.09 before harmonization to 0.003 (ideal: 0, RAVEL/Z_score/GLM/ComBat = 0.087/0.003/0.006/0.013). GM volumes showed no significant difference (P = 0.52) between the reference and HCOBE-harmonized multicenter data. Consistency evaluation showed that AUC values of 0.95 for both reference and HCOBE-harmonized multicenter data (RAVEL/Z_score/GLM/ComBat = 0.86/0.86/0.84/0.89), and the Dice coefficient increased from 0.73 before harmonization to 0.82 (ideal: 1, RAVEL/Z_score/GLM/ComBat = 0.39/0.64/0.59/0.74). DATA CONCLUSION: HCOBE may help to remove scanner variability and could improve the consistency of results in multicenter studies. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.


Assuntos
Doença de Alzheimer , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Substância Cinzenta/diagnóstico por imagem
5.
Diabetes Obes Metab ; 26(4): 1321-1332, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38221859

RESUMO

AIM: This study aimed to assess the efficacy and safety of prusogliptin (DBPR108), a novel and highly selective dipeptidyl peptidase-4 inhibitor, in individuals with type 2 diabetes who had not been using glucose-lowering agents regularly for the 8 weeks before the screening period. MATERIALS AND METHODS: In this multicentre, randomized, double-blind, phase 3 study, adult patients with type 2 diabetes were randomly assigned to receive either DBPR108 100 mg, sitagliptin 100 mg, or placebo once daily during the initial 24-week double-blind treatment period, followed by a 28-week open-label extension period during which all patients received DBPR108 100 mg once daily. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) levels from baseline to week 24. RESULTS: In total, 766 patients were enrolled and received DBPR108 100 mg (n = 462), sitagliptin 100 mg (n = 152), or placebo (n = 152). The mean age of all patients was 54.3 ± 10.5 years, with 58% being men. The median duration of type 2 diabetes was 0.38 (0.02, 2.65) years, and the mean HbA1c (SD) at baseline was 7.94% (0.62), 7.88% (0.61) and 7.83% (0.59) for DBPR108, sitagliptin and placebo groups, respectively. At week 24, the least square mean (SE) changes from baseline in HbA1c were -0.63% (0.04%) for DBPR108, -0.60% (0.07%) for sitagliptin and -0.02% (0.07%) for placebo. The mean treatment difference between DBPR108 and placebo was -0.61% (95% CI -0.77% to -0.44%), and between DBPR108 and sitagliptin was -0.03% (95% CI -0.19% to 0.13%). These results indicate that DBPR108 was superior to placebo and non-inferior to sitagliptin. DBPR108 also significantly reduced fasting and postprandial plasma glucose levels and had little effect on body weight. The mean (SD) changes in HbA1c from baseline to week 52 were -0.50% (0.97%) for the DBPR108 group, -0.46% (0.96%) for the sitagliptin group and -0.41% (0.95%) for the placebo group. The incidence of adverse events was comparable across all three groups. CONCLUSIONS: DBPR108 showed superiority to placebo and non-inferiority to sitagliptin in terms of glycaemic control over the initial 24 weeks in treatment-naïve patients with type 2 diabetes. Furthermore, its efficacy was sustained for up to 52 weeks.


Assuntos
Butanos , Diabetes Mellitus Tipo 2 , Metformina , Nitrilas , Pirrolidinas , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Feminino , Hemoglobinas Glicadas , Quimioterapia Combinada , Hipoglicemiantes/efeitos adversos , Fosfato de Sitagliptina/efeitos adversos , Resultado do Tratamento , Método Duplo-Cego , Metformina/uso terapêutico
6.
Appl Opt ; 63(9): 2324-2330, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38568588

RESUMO

Optical hiding often requires the selection of specific artificial optical components as carriers, which results in poor versatility of the carriers and high costs for the hiding system. To conceal secret information on different surfaces such as metal, wood, and paper, we propose an optical information hiding method. In this method, we use images of surfaces, whose grayscale histograms have the characteristic of symmetric distribution. Based on this characteristic, we first scramble the surface image, and then adjust part of the gray value of the surface image to the complementary value to embed the secret information into a scrambled surface image to generate a key image. In the extraction process, a projector is used to reproduce the scrambled surface image and the key image, which are then incoherently superimposed to extract the secret information using the human visual system. The extraction process does not require complex optical knowledge and is simple and feasible. Simulation experiments and optical experiments indicate that this method is applicable in practice and possesses good security and imperceptibility. Furthermore, we prove the reliability of this method by embedding secret information in different surface images, demonstrating the potential application of more surface images in the field of optical information hiding. Finally, we discuss the applicability of surface information images and analyze the imperceptibility of key images.

7.
J Integr Plant Biol ; 66(7): 1408-1426, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38578160

RESUMO

Structural variations (SVs) are a feature of plant genomes that has been largely unexplored despite their significant impact on plant phenotypic traits and local adaptation to abiotic and biotic stress. In this study, we employed woolly grape (Vitis retordii), a species native to the tropical and subtropical regions of East Asia with both coastal and inland habitats, as a valuable model for examining the impact of SVs on local adaptation. We assembled a haplotype-resolved chromosomal reference genome for woolly grape, and conducted population genetic analyses based on whole-genome sequencing (WGS) data from coastal and inland populations. The demographic analyses revealed recent bottlenecks in all populations and asymmetric gene flow from the inland to the coastal population. In total, 1,035 genes associated with plant adaptive regulation for salt stress, radiation, and environmental adaptation were detected underlying local selection by SVs and SNPs in the coastal population, of which 37.29% and 65.26% were detected by SVs and SNPs, respectively. Candidate genes such as FSD2, RGA1, and AAP8 associated with salt tolerance were found to be highly differentiated and selected during the process of local adaptation to coastal habitats in SV regions. Our study highlights the importance of SVs in local adaptation; candidate genes related to salt stress and climatic adaptation to tropical and subtropical environments are important genomic resources for future breeding programs of grapevine and its rootstocks.


Assuntos
Vitis , Vitis/genética , Adaptação Fisiológica/genética , Genoma de Planta/genética , Genética Populacional , Polimorfismo de Nucleotídeo Único/genética , Tolerância ao Sal/genética , Variação Estrutural do Genoma/genética , Genômica , Genes de Plantas
8.
Opt Express ; 31(8): 13154-13168, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37157459

RESUMO

In this paper, a joint signal processing scheme including a subband multiple-mode full permutation carrierless amplitude phase modulation (SMMP-CAP), signal-to-noise ratio weighted detector (SNR-WD), and multi-channel decision feedback equalizer (MC-DFE) is proposed to mitigate the bandwidth limitation of a high-speed long-reach underwater wireless optical communication (UWOC) system. Referring to the trellis coded modulation (TCM) subset division strategy, 16 quadrature amplitude modulation (QAM) mapping set is divided into four 4-QAM mapping subsets by SMMP-CAP scheme. An SNR-WD and an MC-DFE are employed to enhance the demodulation effect of this system in a fading channel. In a laboratory experiment, the minimal required received optical powers (ROPs) for data rates of 480 Mbps, 600 Mbps, and 720 Mbps, at hard-decision forward error correction (HD-FEC) threshold of 3.80 × 10-3, are -32.7 dBm, -31.3 dBm, and -25.5 dBm, respectively. Moreover, the proposed system successfully achieves a data rate of 560 Mbps in a swimming pool with a transmission distance up to 90 m and a total attenuation measured to be 54.64 dB. To the best of our knowledge, this is the first time to demonstrate a high-speed, long-distance UWOC system by employing an SMMP-CAP scheme.

9.
Opt Lett ; 48(21): 5615-5618, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910716

RESUMO

Data transmission based on the transmission matrix method has realized the multiplexing of a large number of orbital angular momentum (OAM) modes under scattering, which encodes the data by modulating the amplitude of the OAM modes. However, this amplitude modulation (amplitude encoding) method has obvious cross talk when the number of output modes is small, resulting in a non-negligible bit error rate. Here, a multi-channel data transmission method based on OAM phase modulation (phase encoding) under scattering is proposed. This method can resist the multiple-scattering effect of multimode fibers and realize accurate data transmission with very few rows of camera pixels for output mode measurement, which is suitable for high-speed data transmission under scattering. Experimentally, we have achieved a bit error rate of less than 0.005% in the data transmission of a color image through a 60 m multimode fiber with only 2 rows of camera pixels for output mode measurement. Experiments also showed that the proposed method has a higher stability than amplitude encoding when the proportion of "1" or "0" in the code changes.

10.
Eur J Nucl Med Mol Imaging ; 51(1): 159-167, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37668706

RESUMO

PURPOSE: The exact phenoconversion time from isolated rapid eye movement (REM) sleep behavior disorder (iRBD) to synucleinopathies remains unpredictable. This study investigated whole-brain dopaminergic damage pattern (DDP) with disease progression and predicted phenoconversion time in individual patients. METHODS: Age-matched 33 iRBD patients and 20 healthy controls with 11C-CFT-PET scans were enrolled. The patients were followed up 2-10 (6.7 ± 2.0) years. The phenoconversion year was defined as the base year, and every 2 years before conversion was defined as a stage. Support vector machine with leave-one-out cross-validation strategy was used to perform prediction. RESULTS: Dopaminergic degeneration of iRBD was found to occur about 6 years before conversion and then abnormal brain regions gradually expanded. Using DDP, area under curve (AUC) was 0.879 (90% sensitivity and 88.3% specificity) for predicting conversion in 0-2 years, 0.807 (72.7% sensitivity and 83.3% specificity) in 2-4 years, 0.940 (100% sensitivity and 84.6% specificity) in 4-6 years, and 0.879 (100% sensitivity and 80.7% specificity) over 6 years. In individual patients, predicted stages correlated with whole-brain dopaminergic levels (r = - 0.740, p < 0.001). CONCLUSION: Our findings suggest that DDP could accurately predict phenoconversion time of individual iRBD patients, which may help to screen patients for early intervention.


Assuntos
Transtorno do Comportamento do Sono REM , Humanos , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Dopamina , Progressão da Doença
11.
Connect Tissue Res ; 64(2): 117-125, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35876483

RESUMO

PURPOSE: Currently, new loci related to handgrip strength have been identified in genome-wide association studies. However, this topic is an understudied area in the Chinese population. MATERIALS AND METHODS: A total of 135 dizygotic twin pairs recruited from the Qingdao Twin Registry system were included in the present study. Using GEMMA, VEAGSE2, and PASCAL software for SNP-based analysis, gene-based analysis, and pathway-based analysis, respectively. The resulting SNPs were subjected to eQTL analysis. RESULTS: Although none of the loci reach the statistically significant level (p < 5 × 10-8), we found 19 SNPs exceeding the suggestive significant level (p < 1 × 10-5). After imputation, 162 SNPs reached suggestive evidence level for handgrip strength. A total of 1,118 genes reached the nominal significance level (p < 0.05) in gene-based analysis. A total of 626 potential biological pathways were associated with handgrip strength (p < 0.05). The results of eQTL analysis were mainly enriched in tissues such as the muscle-skeletal, brain, visceral fat, and brain-cortical. CONCLUSIONS: Genetic variants may involve in regulatory domains, functional genes, and biological pathways that mediate handgrip strength.


Assuntos
Estudo de Associação Genômica Ampla , Força da Mão , Adulto , Humanos , População do Leste Asiático , Músculos , Polimorfismo de Nucleotídeo Único
12.
Inflamm Res ; 72(8): 1551-1565, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37433890

RESUMO

BACKGROUND: The purpose of this study was to study the effect of STING-IFN-I pathway on incision induced postoperative pain in rats and its possible mechanisms. METHODS: The pain thresholds were evaluated by measuring the mechanical withdrawal threshold and the thermal withdrawal latency. The satellite glial cell and macrophage of DRG were analyzed. The expression of STING, IFN-a, P-P65, iNOS, TNF-α, IL-1ß and IL-6 in DRG was evaluated. RESULTS: The activation of STING-IFN-I pathway can reduce the mechanical hyperalgesia, thermal hyperalgesia, down-regulate the expression of P-P65, iNOS, TNF-α, IL-1ß and IL-6, and inhibit the activation of satellite glial cell and macrophage in DRG. CONCLUSIONS: The activation of STING-IFN-I pathway can alleviate incision induced acute postoperative pain by inhibiting the activation of satellite glial cell and macrophage, which reducing the corresponding neuroinflammation in DRG.


Assuntos
Gânglios Espinais , Fator de Necrose Tumoral alfa , Ratos , Animais , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Doenças Neuroinflamatórias , Hiperalgesia/metabolismo , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/metabolismo
13.
Physiol Plant ; 175(3): e13924, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37158623

RESUMO

Interconduit pit membranes, which are permeable regions in the primary cell wall that connect to adjacent conduits, play a crucial role in water relations and the movement of nutrients between xylem conduits. However, how pit membrane characteristics might influence water-carbon coupling remains poorly investigated in cycads. We examined pit characteristics, the anatomical and photosynthetic traits of 13 cycads from a common garden, to determine if pit traits and their coordination are related to water relations and carbon economy. We found that the pit traits of cycads were highly variable and that cycads exhibited a similar tradeoff between pit density and pit area as other plant lineages. Unlike other plant lineages (1) pit membranes, pit apertures, and pit shapes of cycads were not coordinated as in angiosperms; (2) cycads exhibited larger pit membrane areas but lower pit densities relative to ferns and angiosperms, but smaller and similar pit membrane densities to non-cycad gymnosperms; (3) cycad pit membrane areas and densities were partially coordinated with anatomical traits, with hydraulic supply of the rachis positively coordinated with photosynthesis, whereas pit aperture areas and fractions were negatively coordinated with photosynthetic traits; (4) cycad pit traits reflected adaptation to wetter habitats for Cycadaceae and drier habitats for Zamiaceae. The large variation in pit traits, the unique pit membrane size and density, and the partial coordination of pit traits with anatomical and physiological traits of the rachis and pinna among cycads may have facilitated their dominance in a variety of ecosystems from the Mesozoic to modern times.


Assuntos
Cycadopsida , Ecossistema , Cycadopsida/metabolismo , Fotossíntese , Plantas/metabolismo , Água/metabolismo , Carbono
14.
Twin Res Hum Genet ; 26(1): 26-30, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36852647

RESUMO

An abnormal alanine aminotransferase (ALT) level is predictive of disease and all-cause mortality and may indicate liver injury. Using twin modeling, the genetic and environmental factors that affect human serum ALT levels have been well studied for the populations in the different countries, and the results showed moderate-to-high heritability. However, the heritability of ALT level has not been explored in Chinese population. Thus, we recruited 369 pairs of twins (233 monozygotic and 136 dizygotic) from the Qingdao Twin Registry in China with a median age of 50 years (40-80 years). Correlation analysis and a structural equation model (SEM) were conducted to evaluate the heritability of ALT level. The data for age, gender, body mass index and alcohol consumption were set as covariates. Intrapair correlation in monozygotic twins was 0.64 (95%CI [.56, .71]) and 0.42 (95% CI [.28, .55]) in dizygotic twins. The SEM analysis indicated that 65% (95% CI [57%, 71%]) of the variation in ALT levels can be explained by additive genetics and 35% (95% CI [29%, 44%]) of the variation is attributed to unique environmental factors or residuals. Shared environmental influences were not significant. In conclusion, serum ALT variations exhibited strong genetic effects. The variation could also be explained by unique environmental factors. However, shared environmental factors have a minor impact on the serum ALT level.


Assuntos
População do Leste Asiático , Gêmeos Monozigóticos , Humanos , Pessoa de Meia-Idade , Alanina Transaminase/genética , Gêmeos Monozigóticos/genética , Gêmeos Dizigóticos/genética , Consumo de Bebidas Alcoólicas
15.
Twin Res Hum Genet ; 26(3): 219-222, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37170793

RESUMO

Almost all creatinine is excreted by the kidney in individuals. Serum creatinine concentration, a widely used renal function index in clinical practice, can be affected by both genetic and environmental factors, as evidenced by current research exploring the relationship between these factors and kidney function. However, few studies have explored the heritability of serum creatinine in Asian populations. Therefore, we explored the genetic and environmental factors that affect the serum creatinine level in Asian populations. Participants in this study came from the Qingdao Twin Registry in China, and 374 pairs of twins were included, of which 139 pairs were dizygotic twins, whose ages ranged from 40 to 80 years old, and the serum creatinine level ranged from 10 to 126 µmol/L. Structural equation models were constructed using Mx software to calculate heritability, with adjusted covariates being age, sex, and body mass index. The results of heritability analysis showed that ACE was the best fit model. Serum creatinine level is influenced by genetic and environmental factors. The result of heritability was 35.44%, and the influence of shared environmental factors accounted for 52.13%. This study provided the relevant basis for future research on genetic and environmental factors affecting serum creatinine levels in Asian populations.


Assuntos
População do Leste Asiático , Gêmeos Dizigóticos , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Creatinina , Gêmeos Dizigóticos/genética , Povo Asiático/genética , Sistema de Registros , Gêmeos Monozigóticos/genética
16.
PLoS Genet ; 16(10): e1009009, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33085662

RESUMO

Drug-resistant mutations often have deleterious impacts on replication fitness, posing a fitness cost that can only be overcome by compensatory mutations. However, the role of fitness cost in the evolution of drug resistance has often been overlooked in clinical studies or in vitro selection experiments, as these observations only capture the outcome of drug selection. In this study, we systematically profile the fitness landscape of resistance-associated sites in HIV-1 protease using deep mutational scanning. We construct a mutant library covering combinations of mutations at 11 sites in HIV-1 protease, all of which are associated with resistance to protease inhibitors in clinic. Using deep sequencing, we quantify the fitness of thousands of HIV-1 protease mutants after multiple cycles of replication in human T cells. Although the majority of resistance-associated mutations have deleterious effects on viral replication, we find that epistasis among resistance-associated mutations is predominantly positive. Furthermore, our fitness data are consistent with genetic interactions inferred directly from HIV sequence data of patients. Fitness valleys formed by strong positive epistasis reduce the likelihood of reversal of drug resistance mutations. Overall, our results support the view that strong compensatory effects are involved in the emergence of clinically observed resistance mutations and provide insights to understanding fitness barriers in the evolution and reversion of drug resistance.


Assuntos
Farmacorresistência Viral/genética , Epistasia Genética , Infecções por HIV/tratamento farmacológico , Protease de HIV/genética , HIV-1/genética , Aptidão Genética/genética , Infecções por HIV/genética , Infecções por HIV/virologia , Protease de HIV/efeitos dos fármacos , HIV-1/efeitos dos fármacos , HIV-1/patogenicidade , Humanos , Mutação/genética , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/uso terapêutico , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética
17.
Eur J Nucl Med Mol Imaging ; 49(9): 3073-3085, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35258689

RESUMO

PURPOSE: A unique advantage of the brain positron emission tomography (PET) imaging is the ability to image different biological processes with different radiotracers. However, the diversity of the brain PET image patterns also makes their spatial normalization challenging. Since structural MR images are not always available in the clinical practice, this study proposed a PET-only spatial normalization method based on adaptive probabilistic brain atlas. METHODS: The proposed method (atlas-based method) consists of two parts, an adaptive probabilistic brain atlas generation algorithm, and a probabilistic framework for registering PET image to the generated atlas. To validate this method, the results of MRI-based method and template-based method (a widely used PET-only method) were treated as the gold standard and control, respectively. A total of 286 brain PET images, including seven radiotracers (FDG, PIB, FBB, AV-45, AV-1451, AV-133, [18F]altanserin) and four groups of subjects (Alzheimer disease, Parkinson disease, frontotemporal dementia, and healthy control), were spatially normalized using the three methods. The results were then quantitatively compared by using correlation analysis, meta region of interest (meta-ROI) standardized uptake value ratio (SUVR) analysis, and statistical parametric mapping (SPM) analysis. RESULTS: The Pearson correlation coefficient between the images computed by atlas-based method and the gold standard was 0.908 ± 0.005. The relative error of meta-ROI SUVR computed by atlas-based method was 2.12 ± 0.18%. Compared with template-based method, atlas-based method was also more consistent with the gold standard in SPM analysis. CONCLUSION: The proposed method provides a unified approach to spatially normalize brain PET images of different radiotracers accurately without MR images. A free MATLAB toolbox for this method has been provided.


Assuntos
Doença de Alzheimer , Tomografia por Emissão de Pósitrons , Algoritmos , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos
18.
Diabetes Obes Metab ; 24(11): 2232-2240, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35791646

RESUMO

AIM: To evaluate the efficacy and safety of DBPR108 (prusogliptin), a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, as an add-on therapy in patients with type 2 diabetes (T2D) that is inadequately controlled with metformin. MATERIALS AND METHODS: In this 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2D patients with HbA1c levels ranging from 7.0% to 9.5% on stable metformin were enrolled and randomized (2:1) into the DBPR108 + metformin and placebo + metformin groups. The primary endpoint was the change from baseline in HbA1c at week 24 of DBPR108 versus placebo as an add-on therapy to metformin. RESULTS: At week 24, the least-square mean (standard error) change from baseline in HbA1c was significantly greater in the DBPR108 group (-0.70% [0.09%]) than in the placebo group (-0.07% [0.11%]) (P < .001), with a treatment difference of -0.63% (95% confidence interval: -0.87%, -0.39%) on the full analysis set. A higher proportion of patients achieved an HbA1c of 6.5% or less (19.7% vs. 8.5%) and an HbA1c of 7.0% or less (50.0% vs. 21.1%) at week 24 in the DBPR108 + metformin group. Furthermore, add-on DBPR108 produced greater reductions from baseline in fasting plasma glucose and 2-hour postprandial plasma glucose without causing weight gain. The overall frequency of adverse events was similar between the two groups. CONCLUSIONS: DBPR108 as add-on therapy to metformin offered a significant improvement in glycaemic control, was superior to metformin monotherapy (placebo) and was safe and well-tolerated in patients with T2D that is inadequately controlled with metformin.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Metformina , Adulto , Glicemia , Butanos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Nitrilas , Pirrolidinas , Resultado do Tratamento
19.
J Org Chem ; 87(24): 16390-16398, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36441970

RESUMO

The Ir(III)-catalyzed ortho-C-H amidation of 2-aroylimidazole derivatives with 2,2,2-trichloroethyl azide (TrocN3) as an amidating reagent is reported. The reaction proceeds smoothly, even at room temperature, and various important functional groups are tolerated. The results of deuterium-labeling experiments indicate that C-H bond cleavage is irreversible and does not appear to be the rate-determining step. The presence of an electron-donating group on the phenyl ring in the 2-aroylimidazole results in a dramatic acceleration in the reaction.

20.
BMC Anesthesiol ; 22(1): 250, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933333

RESUMO

BACKGROUND: Humane treatment requires the provision of appropriate sedation and analgesia during medical diagnosis and treatment. However, limited information is available about the status of procedural analgesic interventions in Chinese hospitals. Therefore, a nationwide survey was established to identify challenges and propose potential improvement strategies. METHODS: Forty-three members of the Pain Group of Chinese Society of Anesthesiology established and reviewed the questionnaire, which included (1) general information on the hospitals, (2) the sedation/analgesia rate in gastrointestinal endoscopy, labor, flexible bronchoscopy, hysteroscopy in China, (3) staff assignments, (4) drug use for procedural analgesic interventions, and (5) difficulties in procedural analgesic interventions. The data were obtained using an online questionnaire sent to the chief anesthesiologists of Chinese hospitals above Grade II or members of the Pain Group of Chinese Society of Anesthesiology. RESULTS: Valid and complete questionnaires were received from 2198 (44.0%) hospitals, of which 64.5% were Grade III. The overall sedation/analgesia rates were as follows: gastroscopy (50.6%), colonoscopy (53.7%), ERCP (65.9%), induced abortion (67.5%), labor (42.3%), hysteroscopy (67.0%) and fiber bronchoscopy (52.6%). Compared with Grade II hospitals, Grade III hospitals had a higher proportion of procedural analgesic interventions services except for induced abortion. On average (median [IQR]), each anesthesiologist performed 5.7 [2.3-11.4] cases per day, with 7.3 [3.2-13.6] performed in Grade III hospitals and 3.4 [1.8-6.8] performed in Grade II hospitals (z = -7.065, p < 0.001). CONCLUSIONS: Chinese anesthesiologists have made great efforts to achieve procedural analgesic interventions, as evidenced by the increased rate. The uneven health care provided by hospitals at different levels and in different regions and the lack of anesthesiologists are the main barriers to optimal procedural analgesic interventions.


Assuntos
Analgesia , Anestesiologia , Analgésicos/uso terapêutico , Feminino , Hospitais , Humanos , Dor , Gravidez
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