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BACKGROUND: The impact of gestational diabetes mellitus (GDM) on incident dementia is unknown. Our aim was to evaluate the relationship between GDM and all-cause dementia and the mediating effects of chronic diseases on this relationship. METHODS: This prospective cohort study included women from the UK Biobank who were grouped based on GDM history. Multivariate Cox proportional hazard models were used to explore the associations between GDM and dementia. We further analysed the mediating effects of chronic diseases on this relationship and the interactions of covariates. RESULTS: A total of 1292 women with and 204,171 women without a history of GDM were included. During a median follow-up period of 45 years after first birth, 2921 women were diagnosed with dementia. Women with a GDM history had a 67% increased risk of incident dementia (hazard ratio 1.67, 95% confidence interval: 1.03-2.69) compared with those without a GDM history. According to mediation analyses, type 2 diabetes, coronary heart disease, chronic kidney disease and comorbidities (diagnosed with any two of the three diseases) explained 34.5%, 8.4%, 5.2% and 18.8% of the mediating effect on the relationship. Subgroup analyses revealed that physical activity modified the association between GDM history and dementia (p for interaction = 0.030). Among physically inactive women, GDM was significantly associated with incident dementia; however, this association was not observed among physically active women. CONCLUSIONS: A history of GDM was associated with a greater risk of incident dementia. Type 2 diabetes partially mediated this relationship. Strategies for dementia prevention might be considered for women with a history of GDM.
Assuntos
Demência , Diabetes Gestacional , Humanos , Feminino , Diabetes Gestacional/epidemiologia , Demência/epidemiologia , Demência/etiologia , Gravidez , Incidência , Estudos Prospectivos , Seguimentos , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Modelos de Riscos Proporcionais , Período Pós-Parto , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Reino Unido/epidemiologiaRESUMO
Maternal high-fat diet intake has profound effects on the long-term health of offspring, predisposing them to a higher susceptibility to obesity and metabolic dysfunction-associated steatotic liver disease. However, the detailed mechanisms underlying the role of a maternal high-fat diet in hepatic lipid accumulation in offspring, especially at the weaning age, remain largely unclear. In this study, female C57BL/6J mice were randomly assigned to either a high-fat diet or a control diet, and lipid metabolism parameters were assessed in male offspring at weaning. Gut microbiota analysis and targeted metabolomics of short-chain fatty acids (SCFAs) in these offspring were further performed. Both in vivo and in vitro studies were conducted to explore the role of butyrate in hepatic cholesterol excretion in the liver and HepG2 cells. Our results showed that maternal high-fat feeding led to obesity and dyslipidemia, and exacerbated hepatic lipid accumulation in the livers of offspring at weaning. We observed significant decreases in the abundance of the Firmicutes phylum and the Allobaculum genus, known as producers of SCFAs, particularly butyrate, in the offspring of dams fed a high-fat diet. Additionally, maternal high-fat diet feeding markedly decreased serum butyrate levels and down-regulated ATP-binding cassette transporters G5 (ABCG5) in the liver, accompanied by decreased phosphorylated AMP-activated protein kinase (AMPK) and histone deacetylase 5 (HADC5) expressions. Subsequent in vitro studies revealed that butyrate could induce ABCG5 activation and alleviate lipid accumulation via the AMPK-pHDAC5 pathway in HepG2 cells. Moreover, knockdown of HDAC5 up-regulated ABCG5 expression and promoted cholesterol excretion in HepG2 cells. In conclusion, our study provides novel insights into how maternal high-fat diet feeding inhibits hepatic cholesterol excretion and down-regulates ABCG5 through the butyrate-AMPK-pHDAC5 pathway in offspring at weaning.
Assuntos
Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Butiratos , Colesterol , Dieta Hiperlipídica , Microbioma Gastrointestinal , Fígado , Camundongos Endogâmicos C57BL , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Butiratos/metabolismo , Humanos , Fígado/metabolismo , Células Hep G2 , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Masculino , Colesterol/metabolismo , Colesterol/sangue , Gravidez , Camundongos , Metabolismo dos Lipídeos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Obesidade/metabolismo , Obesidade/microbiologia , Dislipidemias/metabolismo , Dislipidemias/microbiologia , Dislipidemias/etiologia , LipoproteínasRESUMO
Obesity is a complex disorder, and the incidence of obesity continues to rise at an alarming rate worldwide. In particular, the growing incidence of overweight and obesity in children is a major health concern. However, the underlying mechanisms of obesity remain unclear and the efficacy of several approaches for weight loss is limited. As an important calcium-permeable temperature-sensitive cation channel, transient receptor potential vanilloid (TRPV) ion channels directly participate in thermo-, mechano-, and chemosensory responses. Modulation of TRPV ion channel activity can alter the physiological function of the ion channel, leading to neurodegenerative diseases, chronic pain, cancer, and skin disorders. In recent years, increasing studies have demonstrated that TRPV ion channels are abundantly expressed in metabolic organs, including the liver, adipose tissue, skeletal muscle, pancreas, and central nervous system, which has been implicated in various metabolic diseases, including obesity and diabetes mellitus. In addition, as an important process for the pathophysiology of adipocyte metabolism, adipocyte differentiation plays a critical role in obesity. In this review, we focus on the role of TRPV ion channels in adipocyte differentiation to broaden the ideas for prevention and control strategies for obesity.
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Antineoplásicos , Obesidade Infantil , Criança , Humanos , Diferenciação Celular , Adipócitos , Canais de CálcioRESUMO
Sea anemone venom, abundant in protein and peptide toxins, serves primarily for predatory defense and competition. This study delves into the insulin-like peptides (ILPs) present in sea anemones, particularly focusing on their role in potentially inducing hypoglycemic shock in prey. We identified five distinct ILPs in Exaiptasia diaphana, exhibiting varied sequences. Among these, ILP-Ap04 was successfully synthesized using solid phase peptide synthesis (SPPS) to evaluate its hypoglycemic activity. When tested in zebrafish, ILP-Ap04 significantly reduced blood glucose levels in a model of diabetes induced by streptozotocin (STZ) and glucose, concurrently affecting the normal locomotor behavior of zebrafish larvae. Furthermore, molecular docking studies revealed ILP-Ap04's unique interaction with the human insulin receptor, characterized by a detailed hydrogen-bonding network, which supports a unique mechanism for its hypoglycemic effects. Our findings suggest that sea anemones have evolved sophisticated strategies to activate insulin receptors in vertebrates, providing innovative insights into the design of novel drugs for the treatment of diabetes.
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Venenos de Cnidários , Diabetes Mellitus , Anêmonas-do-Mar , Humanos , Animais , Insulina , Hipoglicemiantes , Peixe-Zebra , Simulação de Acoplamento Molecular , Peptídeos Semelhantes à InsulinaRESUMO
AHP-3a, a triple-helix acidic polysaccharide isolated from Alpinia officinarum Hance, was evaluated for its anticancer and antioxidant activities. The physicochemical properties and structure of AHP-3a were investigated through gel permeation chromatography, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. The weight-average molecular weight of AHP-3a was 484 kDa, with the molar percentages of GalA, Gal, Ara, Xyl, Rha, Glc, GlcA, and Fuc being 35.4%, 21.4%, 16.9%, 11.8%, 8.9%, 3.1%, 2.0%, and 0.5%, respectively. Based on the results of the monosaccharide composition analysis, methylation analysis, and NMR spectroscopy, the main chain of AHP-3a was presumed to consist of (1â4)-α-D-GalpA and (1â2)-α-L-Rhap residues, which is a pectic polysaccharide with homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) structural domains containing side chains. In addition, the results of the antioxidant activity assay revealed that the ability of AHP-3a to scavenge DPPH, ABTS, and OH free radicals increased with an increase in its concentration. Moreover, according to the results from the EdU, wound healing, and Transwell assays, AHP-3a can control the proliferation, migration, and invasion of HepG2 and Huh7 hepatocellular carcinoma cells without causing any damage to healthy cells. Thus, AHP-3a may be a natural antioxidant and anticancer component.
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Alpinia , Antioxidantes , Compostos de Bifenilo , Polissacarídeos , Alpinia/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Células Hep G2 , Peso Molecular , Linhagem Celular Tumoral , Monossacarídeos/análise , Monossacarídeos/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Picratos/química , Picratos/antagonistas & inibidores , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Methane is the second largest anthropogenic greenhouse gas, and changes in atmospheric methane concentrations can reflect the dynamic balance between its emissions and sinks. Therefore, the monitoring of CH4 concentration changes and the assessment of underlying driving factors can provide scientific basis for the government's policy making and evaluation. China is the world's largest emitter of anthropogenic methane. However, due to the lack of ground-based observation sites, little work has been done on the spatial-temporal variations for the past decades and influencing factors in China, especially for areas with high anthropogenic emissions as Central and Eastern China. Here to quantify atmospheric CH4 enhancements trends and its driving factors in Central and Eastern China, we combined the most up-to-date TROPOMI satellite-based column CH4 (xCH4) concentration from 2018 to 2022, anthropogenic and natural emissions, and a random forest-based machine learning approach, to simulate atmospheric xCH4 enhancements from 2001 to 2018. The results showed that (1) the random forest model was able to accurately establish the relationship between emission sources and xCH4 enhancement with a correlation coefficient (R²) of 0.89 and a root mean-square error (RMSE) of 11.98 ppb; (2)The xCH4 enhancement only increased from 48.21±2.02 ppb to 49.79±1.87 ppb from the year of 2001 to 2018, with a relative change of 3.27%±0.13%; (3) The simulation results showed that the energy activities and waste treatment were the main contributors to the increase in xCH4 enhancement, contributing 68.00% and 31.21%, respectively, and the decrease of animal ruminants contributed -6.70% of its enhancement trend.
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Metano , Animais , Metano/análise , ChinaRESUMO
Maternal overnutrition can dramatically increase the susceptibility of offspring to metabolic diseases, whereas maternal exercise may improve glucose metabolism in offspring. However, the underlying mechanism programming the intergenerational effects of maternal exercise on the benefits of glucose metabolism has not been fully elaborated. C57BL/6 female mice were randomly assigned to four subgroups according to a diet and exercise paradigm before and during pregnancy as follows: NC (fed with normal chow diet and sedentary), NCEx (fed with normal chow diet and running), HF (fed with high-fat diet and sedentary), and HFEx (fed with high-fat diet and running). Integrative 16S rDNA sequencing and mass spectrometry-based metabolite profiling were synchronously performed to characterize the effects of maternal exercise on the gut microbiota composition and metabolite alterations in offspring. Maternal exercise, acting as a natural pharmaceutical intervention, prevented deleterious effects on glucose metabolism in offspring. 16S rDNA sequencing revealed remarkable changes in the gut microbiota composition in offspring. Metabolic profiling indicated multiple altered metabolites, which were enriched in butanoate metabolism signaling in offspring. We further found that maternal exercise could mediate gene expression related to intestinal gluconeogenesis in offspring. In conclusion, our study indicated that maternal running significantly improved glucose metabolism in offspring and counteracted the detrimental effects of maternal high-fat feeding before and during pregnancy. We further demonstrated that maternal voluntary wheel running could integratively program the gut microbiota composition and fecal metabolite changes and then regulate butanoate metabolism and mediate intestinal gluconeogenesis in offspring.
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Microbioma Gastrointestinal , Camundongos , Gravidez , Animais , Feminino , Atividade Motora , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , HomeostaseRESUMO
AIM: To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point self-measured blood glucose. METHODS: Two phase III trials were analysed. LixiLan-O-AP was performed in insulin-naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-of-treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time-in-range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time-below-the-range [dTBR] and < 25% derived time-above-the-range [dTAR]) were calculated. RESULTS: The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD1 : 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD2 : 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan-O-AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan-L-CN. In LixiLan-O-AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan-L-CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi. CONCLUSION: iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin-naïve and insulin-experienced AP people with T2D.
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Diabetes Mellitus Tipo 2 , Humanos , Insulina Glargina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/uso terapêutico , Hemoglobinas Glicadas , Combinação de Medicamentos , Glicemia , Insulina/uso terapêutico , Insulina Regular HumanaRESUMO
Triticum boeoticum (2n = 2x = 14, AbAb) is an important relative of wheat. This species tolerates many different types of environmental stresses, including drought, salt, and pathogenic infection, and is lower in dietary fiber and higher in antioxidants, protein (15 to 18%), lipids, and trace elements than common wheat. However, the gene transfer rate from this species to common wheat is low, and few species-specific molecular markers are available. In this study, the wheat-T. boeoticum substitution line Z1889, derived from a cross between the common wheat cultivar Crocus and T. boeoticum line G52, was identified using multicolor fluorescence in situ hybridization, multicolor genomic in situ hybridization, and a 55K single-nucleotide polymorphism array. Z1889 was revealed to be a 4Ab (4B) substitution line with a high degree of resistance to stripe rust pathogen strains prevalent in China. In addition, 22 4Ab chromosome-specific molecular markers and 11 T. boeoticum genome-specific molecular markers were developed from 1,145 4Ab chromosome-specific fragments by comparing the sequences generated by specific-length amplified fragment sequencing, with an efficiency of up to 55.0%. Furthermore, the specificity of these markers was verified in four species containing the Ab genome. These markers not only can be used for the detection of the 4Ab chromosome but also provide a basis for molecular marker-assisted, selection-based breeding in wheat.
Assuntos
Basidiomycota , Triticum , Triticum/genética , Hibridização in Situ Fluorescente , Resistência à Doença/genética , Melhoramento Vegetal , Basidiomycota/genética , Marcadores GenéticosRESUMO
Lodging is one of the most important factors affecting the high and stable yield of wheat worldwide. Solid-stemmed wheat has higher stem strength and lodging resistance than hollow-stemmed wheat does. There are many solid-stemmed varieties, landraces, and old varieties of durum wheat. However, the transfer of solid stem genes from durum wheat is suppressed by a suppressor gene located on chromosome 3D in common wheat, and only hollow-stemmed lines have been created. However, synthetic hexaploid wheat can serve as a bridge for transferring solid stem genes from tetraploid wheat to common wheat. In this study, the F1, F2, and F2:3 generations of a cross between solid-stemmed Syn-SAU-119 and semisolid-stemmed Syn-SAU-117 were developed. A single dominant gene, which was tentatively designated Su-TdDof and suppresses stem solidity, was identified in synthetic hexaploid wheat Syn-SAU-117 by using genetic analysis. By using bulked segregant RNA-seq (BSR-seq) analysis, Su-TdDof was mapped to chromosome 7DS and flanked by markers KASP-669 and KASP-1055 within a 4.53 cM genetic interval corresponding to 3.86 Mb and 2.29 Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Ae. tauschii (AL8/78 v4.0) genomes, respectively, in which three genes related to solid stem development were annotated. Su-TdDof differed from a previously reported solid stem suppressor gene based on its origin and position. Su-TdDof would provide a valuable example for research on the suppression phenomenon. The flanking markers developed in this study might be useful for screening Ae. tauschii accessions with no suppressor gene (Su-TdDof) to develop more synthetic hexaploid wheat lines for the breeding of lodging resistance in wheat and further cloning the suppressor gene Su-TdDof.
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Melhoramento Vegetal , Triticum , Genes Dominantes , Poaceae , Triticum/genética , ChinaRESUMO
OBJECTIVES: The study aimed to investigate the prevalence and demographic characteristics of an immune checkpoint inhibitor (ICI)-related thyroid dysfunction (ICI-TD), and to explore risk factors of poor clinical outcome using data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). METHODS: This is a retrospective study. All cases, aged over 18-year olds, of new-onset or new-diagnosed thyroid dysfunction related to FDA-approved ICIs from January 1, 2011 to December 31, 2020 were identified using FAERS. Data of age, gender, other combined endocrinopathies related to ICIs besides ICI-TDs, and the prognosis was analyzed. RESULTS: In total, 2.60% (2971/114 121) cases of ICI-TDs were identified. Among them, 1842 (62.0%) developed hypothyroidism, 675 (22.7%) were hyperthyroidism, and 454 (15.3%) presented in thyroiditis without the mention of thyroid function. Patients on anti- programmed cell death protein-1 (PD-1) therapy displayed higher risk of hypothyroidism compared with other 3 regimens, respectively (P < .01 for all). The likelihood of other immune-related endocrinopathies in patients on the combination therapy of anti-cytotoxic T-cell-associated protein-4 (CTLA-4) and anti-PD-1 was significantly elevated than anti-PD-1 (odds ratio [OR] 2.362, 95% confidence interval [CI] [1.925-2.898], P < .001) and anti-programmed death-ligand 1 (PD-L1) regimens (OR 4.857, 95%CI [3.228-7.308], P < .001). The risk of severe cases was positively related to hypothyroidism in individuals on anti-PD-1 therapy (OR 1.587, 95%CI [1.146-2.197], P = .005) and those on anti-CTLA-4 therapy (OR 3.616, 95%CI [1.285-10.171], P = .015). The risk of severe cases was positively associated with the comorbidity with other endocrinopathies (anti-PD-1 group, OR 0.285, 95%CI [0.200-0.467], P < .001; anti-PD-1+anti-CTLA-4 group, OR 0.574, 95%CI [0.371-0.890], P = .013). CONCLUSIONS: Regular monitor of thyroid function is indispensable, since ICI-TDs manifested as hypothyroidism or hyperthyroidism, especially those on the combination therapy. Awareness among health care professionals is critical when hypothyroidism occurs, which might indicate poor clinical outcomes.
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Doenças do Sistema Endócrino , Hipertireoidismo , Hipotireoidismo , Doenças da Glândula Tireoide , Idoso , Humanos , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/epidemiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/epidemiologia , Estados Unidos/epidemiologia , United States Food and Drug AdministrationRESUMO
OBJECTIVE: Measurements of plasma free metanephrines (MNs), including MN and normetanephrine, provide high sensitivity and specificity for the diagnosis of pheochromocytoma and paraganglioma (PPGL). 3-Methoxytyramine (3-MT) and chromogranin A (CgA) may allow the detection of dopamine-producing or biochemically silent PPGL. The aim of this study was to evaluate whether measurements of plasma 3-MT or CgA as a supplement of plasma MNs offer a better diagnostic strategy for initial testing of PPGL. PATIENTS AND DESIGN: We enroled 125 patients who underwent surgery from 2015 to 2016 for our study and identified 33 patients with PPGL and 92 patients with non-PPGL masses. MEASUREMENT: The levels of plasma free MNs and 3-MT were measured for all 125 patients using liquid chromatography-tandem mass spectrometry. Plasma CgA concentrations were determined using a radioimmunoassay. To evaluate the diagnostic performance of plasma free MNs, 3-MT and CgA, sensitivity and specificity were determined, and receiver operating characteristic curves were constructed. RESULTS: We found that combining 3-MT and MNs increased the diagnostic sensitivity from 93.9% (95% confidence interval [CI]: 78.4%-98.9%) to 97.0% (95% CI: 82.5%-99.8%). In contrast, addition of plasma CgA test reduced the diagnostic specificity significantly from 91.3% (95% CI: 83.1%-95.9%) to 75.0% (95% CI: 64.7%-83.2%). CONCLUSION: Here, we demonstrated that 3-MT represents a valuable supplementary test to plasma MNs, which can further enhance the sensitivity of the assay, while plasma CgA added no additional diagnostic value to MNs due to the lowered diagnostic specificity.
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Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico , Cromogranina A , Dopamina/análogos & derivados , Humanos , Metanefrina , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Sensibilidade e EspecificidadeRESUMO
AIMS: To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs. MATERIALS AND METHODS: LixiLan-L-CN (NCT03798080) was a 30-week randomized, active-controlled, open-label, parallel-group, multicentre study. Participants were randomized 1:1 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30. RESULTS: In total, 426 participants were randomized to iGlarLixi (n = 212) or iGlar (n = 214). Mean age was 58 years, 67% had a body mass index ≥24 kg/m2 , corresponding to overweight/obesity, and the mean diabetes duration was 12.3 years. From mean baseline HbA1c of 8.1% in both groups, greater decreases were seen with iGlarLixi versus iGlar [least squares mean difference: -0.7 (95% confidence interval: -0.9, -0.6)%; p < .0001] to final HbA1c of 6.7% and 7.4%, respectively. HbA1c <7.0% achievement was greater with iGlarLixi (63.3%) versus iGlar (29.9%; p < .0001). Mean body weight decreased with iGlarLixi and increased with iGlar [least squares mean difference: -0.9 (95% confidence interval: -1.4, -0.5) kg; p = .0001]. Hypoglycaemia incidence was similar between groups. Few gastrointestinal adverse events occurred (rated mild/moderate) with a slightly higher incidence with iGlarLixi than iGlar. CONCLUSIONS: iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long-standing T2D advancing therapy from basal insulin.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Adulto , Glicemia , China/epidemiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Combinação de Medicamentos , Hemoglobinas Glicadas/análise , Controle Glicêmico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Peptídeos/uso terapêuticoRESUMO
OBJECTIVE: The study aimed to investigate the attitudes of people with diabetes mellitus (DM) on COVID-19 vaccination and its influence on the glycemic control. METHODS: Data were collected from a consecutive series of adults (age > 18 years) with type 2 diabetes under regular follow-ups in the Integrated Care Diabetes Outpatient Clinic of Peking University First Hospital from December 1st to December 31st 2021. An online interview questionnaire was conducted, and demographic data including age, sex category, history of drug allergy, history of hypertension, the duration of diabetes, reasons for vaccine hesitancy (VH) and adverse reactions after each injection of vaccines was collected. Glucose levels were collected from medical records. RESULTS: Thirty-nine (22.9%) subjects experienced VH and 131 (77.1%) people living with diabetes received inactivated vaccine against COVID-19. Hesitant individuals had a higher proportion of female gender (vaccinated group vs. VH group, 62/131 vs. 26/39, p = 0.044), higher baseline glycosylated hemoglobin A1c (HbA1c) (vaccinated group vs. VH group, 6.56 ± 0.95% vs. 7.54 ± 2.01%, p < 0.001) and elevated baseline postprandial blood glucose (PBG) (vaccinated group vs. VH group, 8.32 ± 1.97 mmol/L vs. 9.44 ± 2.94 mmol/L, p = 0.015). Subjects of male gender (p = 0.025) and history of hypertension (p = 0.021) were likely to get vaccinated, while higher HbA1c was negatively associated with an elevated propensity to receive anti-COVID-19 vaccine (p = 0.003). Most common reasons for hesitating to receive COVID-19 vaccination were worrying about the possibility of leading to other diseases (30.8%), followed by fearing of glucose variation (17.9%). Systemic adverse reactions were reported in 30.5% individuals after the first injection of inactivated vaccines, and resolved within 3 days in medium. Fasting blood glucose (FBG) decreased significantly after the third injection compared with FBG after the second dose (second vs. third, 6.78 ± 1.24 mmol/L vs. 6.41 ± 1.30 mmol/L, p = 0.027). HbA1c reduced significantly from 6.56% before vaccination to 6.35% after the second injection (p = 0.012). CONCLUSIONS: Our study demonstrated that vaccine hesitancy was lower among male subjects and people with hypertension, while vaccine confidence was reduced in people with poor glycemic control. HbA1c level was lower along with vaccination.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Diabetes Mellitus Tipo 2 , Controle Glicêmico , Hesitação Vacinal , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicemia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , População do Leste Asiático , Glucose , VacinaçãoRESUMO
The pathological mechanism of autism spectrum disorder (ASD) remains unclear. Nowadays, surface-based morphometry (SBM) based on structural magnetic resonance imaging (sMRI) techniques have reported cortical thickness (CT) variations in ASD. However, the findings were inconsistent and heterogeneous. This current meta-analysis conducted a whole-brain vertex-wise coordinate-based meta-analysis (CBMA) on CT studies to explore the most noticeable and robust CT changes in ASD individuals by applying the seed-based d mapping (SDM) program. A total of 26 investigations comprised 27 datasets were included, containing 1,635 subjects with ASD and 1470 HC, along with 94 coordinates. Individuals with ASD exhibited significantly altered CT in several regions compared to HC, including four clusters with thicker CT in the right superior temporal gyrus (STG.R), the left middle temporal gyrus (MTG.L), the left anterior cingulate/paracingulate gyri, the right superior frontal gyrus (SFG.R, medial orbital parts), as well as three clusters with cortical thinning including the left parahippocampal gyrus (PHG.L), the right precentral gyrus (PCG.R) and the left middle frontal gyrus (MFG.L). Adults with ASD only demonstrated CT thinning in the right parahippocampal gyrus (PHG.R), revealed by subgroup meta-analyses. Meta-regression analyses found that CT in STG.R was positively correlated with age. Meanwhile, CT in MFG.L and PHG.L had negative correlations with the age of ASD individuals. These results suggested a complicated and atypical cortical development trajectory in ASD, and would provide a deeper understanding of the neural mechanism underlying the cortical morphology in ASD.
RESUMO
As LoRaWAN is one of the most popular long-range wireless protocols among low-power IoT applications, more and more focus is shifting towards security. In particular, physical layer topics become relevant to improve the security of LoRaWAN nodes, which are often limited in terms of computational power and communication resources. To this end, e.g., detection methods for wireless attacks improve the integrity and robustness of LoRaWAN access. Further, wireless physical layer techniques have potential to enhance key refreshment and device authentication. In this work, we aim to provide a comprehensive review of various vulnerabilities, countermeasures and security enhancing features concerning the LoRaWAN physical layer. Afterwards, we discuss the impact of the reviewed topics on LoRaWAN security and, subsequently, we identify research gaps as well as promising future research directions.
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ComunicaçãoRESUMO
BACKGROUND: Clinical guidelines indicate that chronic highland exposure could induce pulmonary hypertension; chronic hepatic disease may affect cardiac structure and functions. However, the simultaneous impact of hepatic echinococcosis (HE) and chronic highland exposure on cardiac structure and function in Tibetan residents are under-investigated. METHODS: One hundred and twenty patients with HE, 23 healthy high-altitude migrants with a mean residence time of 7.15 ± 1.12 years, and 46 healthy Tibetan permanent residents were enrolled in this study. All participants received comprehensive transthoracic echocardiography. RESULTS: High-altitude migrants have a relatively lower pulmonary artery flow velocity (PV) and a slightly higher pulmonary artery mean pressure (PAMP) than the Tibetan permanent residents. Patients with HE presented relatively smaller dimensions of the main pulmonary artery and branches and a bigger right atrium and right ventricular cavity size than the two control groups. PV, PAMP and numbers of detectable tricuspid regurgitation jet velocity (TRJV), right ventricular fractional area change (RV_FAC), tricuspid annular plane systolic excursion (TAPSE), the ratio of tricuspid inflow velocities at early diastole to tricuspid annular early diastolic excursion velocity (RV_E/e') and right ventricular myocardial performance index (RV_MPI) were increased in patients with HE compared to the two control groups. Similarly, decreased LVEF and Impaired left ventricular diastolic function were identified in patients with HE compared to the two control groups. CONCLUSIONS: Patients with HE presented with impaired biventricular contractile performance and diastolic dysfunction.
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Equinococose Hepática , Disfunção Ventricular Direita , Humanos , Estudos de Casos e Controles , Ecocardiografia , Tibet , Função Ventricular DireitaRESUMO
Autoimmune thyroid diseases (AITDs), which include Hashimoto's thyroiditis (HT) and Graves' disease (GD), have a higher prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the literature. The effects of AITD-associated cytokines on SARS-CoV-2 infection-mediating molecule levels might be involved in the pathogenesis of susceptibility. We speculated that hydrogen sulfide (H2S) might attenuate this process since H2S has antiviral effects. Using immunohistochemistry, we found that angiotensin-converting enzyme-II (ACE2) expression was higher in the HT group and neuropilin 1 (NRP1) expression was higher in HT and GD groups than in the normal group, while transmembrane protease serine type 2 (TMPRSS2) expression was lower in HT and GD groups. When culturing primary thyrocytes with cytokines or sodium hydrosulfide (NaHS) plus cytokines, we found that ACE2 and NRP1 mRNA levels were upregulated while TMPRSS2 levels were downregulated by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). After pretreatment with NaHS in thyrocytes, ACE2 and NRP1 expression were downregulated compared to IFN-γ or TNF-α treatment, and NaHS had no effect on TMPRSS2 expression. Our findings suggested that IFN-γ and TNF-α, which are elevated in AITDs, promoted ACE2 and NRP1 expression and inhibited TMPRSS2 expression. H2S might protect against SARS-CoV-2 infection by downregulating ACE2 and NRP1 levels.
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COVID-19 , Doença de Graves , Sulfeto de Hidrogênio , Humanos , SARS-CoV-2 , Fator de Necrose Tumoral alfa/farmacologia , Interferon gama/farmacologia , Enzima de Conversão de Angiotensina 2/genética , Sulfeto de Hidrogênio/farmacologia , Peptidil Dipeptidase A/metabolismoRESUMO
Ixeris chinensis (Thunb.) Nakai (IC) is a folk medicinal herb used in Mongolian medical clinics for the treatment of hepatitis and fatty liver diseases even though its pharmacological mechanism has not been well characterized. This study investigated the hepatoprotective mechanism of IC on mice with nonalcoholic fatty liver disease (NAFLD) by integrating gut microbiota and metabolomic analysis. A high-fat diet (HFD) was used to develop nonalcoholic fatty liver disease, after which the mice were treated with oral IC (0.5, 1.5 and 3.0 g/kg) for 10 weeks. HFD induced NAFLD and the therapeutic effects were characterized by pathological and histological evaluations, and the serum indicators were analyzed by ELISA. The gut microbial and metabolite profiles were studied by 16S rRNA sequencing and untargeted metabolomic analysis, respectively. The results showed that the administration of IC resulted in significant decreases in body weight; liver index; serum biomarkers such as ALT, TG, and LDL-C; and the liver inflammatory factors IL-1ß, IL-6, and TNF-α. The 16S rRNA sequencing results showed that administration of IC extract altered both the composition and abundance of the gut microbiota. Untargeted metabolomic analysis of liver samples detected a total of 212 metabolites, of which 128 were differentially expressed between the HFD and IC group. IC was found to significantly alter the levels of metabolites such as L-glutamic acid, pyridoxal, ornithine, L-aspartic acid, D-proline, and N4-acetylaminobutanal, which are involved in the regulation of glutamine and glutamate, Vitamin B6 metabolism, and arginine and proline metabolic pathways. Correlation analysis indicated that the effects of the IC extract on metabolites were associated with alterations in the abundance of Akkermansiaceae, Lachnospiraceae, and Muribaculaceae. Our study revealed that IC has a potential hepatoprotective effect in NAFLD and that its function might be linked to improvements in the composition of gut microbiota and their metabolites.
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Asteraceae , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Prolina/farmacologia , RNA Ribossômico 16S/genéticaRESUMO
OBJECTIVE: Riedel's thyroiditis (RT) is a very rare chronic fibrosing thyroiditis that is often associated with multifocal fibrosclerosis. Although the relationship of RT and IgG4-related disease (IgG4-RD) has been suggested, the expression of IgG and IgG4 in thyroid tissues of patients with RT has seldom been studied. DESIGN: A case series and literature review. PATIENTS AND MEASUREMENTS: We searched our hospital's pathology database and identified five cases of RT between 2000 and 2019. The expression levels of IgG4 and IgG in thyroid tissues were detected by immunohistochemistry. We also performed a literature search of the electronic databases PubMed/MEDLINE, Web of Science and China National Knowledge Internet (CNKI). Eight papers were included in this study. RESULTS: According to immunohistochemistry, the numbers of IgG4+ plasma cells per high-power field (HPF) of the five RT patients at our hospital were 80, 8, 50, 10 and 22, and the respective IgG4+/IgG+ ratios were 76%, 80%, 43%, 19% and 28%. In the literature, 15 RT patients with confirmed IgG4 and IgG immunohistochemical findings were identified. Only seven of them fulfilled the IgG4-RD diagnostic criteria in terms of immunohistochemistry (IgG4+ > 10/HPF, IgG4+/IgG+ > 40%). In order to ensure that most RT cases can meet the IgG4 immunohistochemical criteria, an organ-specific cut-off value (≥10 IgG4+ plasma cells/HPF and ≥ an IgG4+/IgG ratio of 20%) was finally selected in our study. CONCLUSION: Our findings of IgG4 expression in patients with RT suggest that a cut-off of 10 IgG4+ plasma cells/HPF and an IgG4+/IgG ratio of 20% are more suitable diagnostic criteria for RT in IgG4-RD.