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Climate change significantly affects plant biomass and phenological occurrence time in alpine grasslands of Tibetan Plateau. The changes in phenological periods are closely related to the length of vegetative and reproductive growth periods, which may further affect aboveground biomass accumulation. In this study, based on fixed-point observations of plant biomass and phenology as well as the corresponding climatic data from 1997 to 2020 in the alpine grasslands of Tibetan Plateau, we used statistical methods such as ordinary linear regression and piecewise structural equation model to explore the characteristics of interannual climate change in the study area, the variation trends of plant biomass and phenological periods, and the correlations between biomass and phenological and climatic factors. The results showed that mean annual temperature and annual precipitation in the study area increased significantly from 1997 to 2020, suggesting a clear "warm-wet" trend. Aboveground biomass and relative biomass of Stipa sareptana var. krylovii (the dominant species) decreased significantly. However, absolute and relative biomass of subdominant species (Kobresia humilis) increased significantly, indicating that the dominance of K. humilis increased. The warm-wet climates enhanced aboveground biomass accumulation of K. humilis by extending the period of reproductive growth. Mean annual temperature and annual precipitation decreased aboveground biomass of S. sareptana by shortening the length of vegetative growth period. In a word, the warmer and wetter climate significantly affected aboveground biomass accumulation by regulating the changes in the phenological period, and the interspecific difference in their response resulted in a larger change in community composition. This study area may show a trend from alpine grassland to alpine meadow, and thus further works are urgently needed.
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Biomasa , Cambio Climático , Pradera , Poaceae , Tibet , Poaceae/crecimiento & desarrollo , China , Altitud , EcosistemaRESUMEN
Age-related osteoporosis is characterized by a marked decrease in the number of osteoblasts, which has been partly attributed to the senescence of cells of the osteoblastic lineage. Epigenetic studies have provided new insights into the mechanisms of current osteoporosis treatments and bone repair pathophysiology. N6-methyladenosine (m6A) is a novel transcript modification that plays a major role in cellular senescence and is essential for skeletal development and internal environmental stability. Bioinformatics analysis revealed that the expression of the m6A reading protein Igf2bp2 was significantly higher in osteoporosis patients. However, the role of Igf2bp2 in osteoblast senescence has not been elucidated. In this study, we found that Igf2bp2 levels are increased in ageing osteoblasts induced by multiple repetition and H2O2. Increasing Igf2bp2 expression promotes osteoblast senescence by increasing the stability of Slc1a5 mRNA and inhibiting cell cycle progression. Additionally, Mettl3 was identified as Slc1a5 m6A-methylated protein with increased m6A modification. The knockdown of Mettl3 in osteoblasts inhibits the reduction of senescence, whereas the overexpression of Mettl3 promotes the senescence of osteoblasts. We found that administering Cpd-564, a specific inhibitor of Mettl3, induced increased bone mass and decreased bone marrow fat accumulation in aged rats. Notably, in an OVX rat model, Igf2bp2 small interfering RNA delivery also induced an increase in bone mass and decreased fat accumulation in the bone marrow. In conclusion, our study demonstrated that the Mettl3/Igf2bp2-Slc1a5 axis plays a key role in the promotion of osteoblast senescence and age-related bone loss.
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Adenosina , Senescencia Celular , Metiltransferasas , Osteoblastos , Osteoporosis , Proteínas de Unión al ARN , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , Animales , Senescencia Celular/efectos de los fármacos , Metiltransferasas/metabolismo , Metiltransferasas/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Osteoporosis/metabolismo , Osteoporosis/patología , Osteoporosis/genética , Ratones , Humanos , RatasRESUMEN
BACKGROUND: Pituitary gland metastasis is an unusual event, and pituitary metastasis from lung adenocarcinoma is extremely rare and associated with poor prognosis. To date, approximately 15 cases have been reported. CASE SUMMARY: Here, we present the case of a 64-year-old woman with pituitary metastasis derived from lung adenocarcinoma, which was difficult to distinguish from other sellar tumors. The patient presented to the neurosurgery clinic with blurred vision and intermittent headache. During hospitalization, brain computed tomography (CT) and magnetic resonance imaging revealed a pituitary macroadenoma. Chest CT revealed irregular nodules in the basal segment of the lower lobe of the left lung, which were likely lung cancer. Positron emission tomography-CT revealed a carbohydrate metabolism tumor in the lungs and sellar region, which was considered malignant. Postoperative pathological examination of the sellar tumor revealed lung adenocarcinoma. CONCLUSION: Excision of pituitary metastases combined with radiotherapy and chemotherapy should be a priority treatment for patients with pituitary metastasis.
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Gut microbes is a crucial factor in the pathogenesis of type 1 diabetes (T1D). However, it is still unclear which gut microbiota are the key factors affecting T1D and their influence on the development and progression of the disease. To fill these knowledge gaps, we constructed a model to find biomarker from gut microbiota in patients with T1D. We first identified microbial markers using Linear discriminant analysis Effect Size (LEfSe) and random forest (RF) methods. Furthermore, by constructing co-occurrence networks for gut microbes in T1D, we aimed to reveal all gut microbial interactions as well as major beneficial and pathogenic bacteria in healthy populations and type 1 diabetic patients. Finally, PICRUST2 was used to predict Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways and KO gene levels of microbial markers to investigate the biological role. Our study revealed that 21 identified microbial genera are important biomarker for T1D. Their AUC values are 0.962 and 0.745 on discovery set and validation set. Functional analysis showed that 10 microbial genera were significantly positively associated with D-arginine and D-ornithine metabolism, spliceosome in transcription, steroid hormone biosynthesis and glycosaminoglycan degradation. These genera were significantly negatively correlated with steroid biosynthesis, cyanoamino acid metabolism and drug metabolism. The other 11 genera displayed an inverse correlation. In summary, our research identified a comprehensive set of T1D gut biomarkers with universal applicability and have revealed the biological consequences of alterations in gut microbiota and their interplay. These findings offer significant prospects for individualized management and treatment of T1D.
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Diabetes Mellitus Tipo 1 , Microbioma Gastrointestinal , Aprendizaje Automático , Humanos , Microbioma Gastrointestinal/genética , Diabetes Mellitus Tipo 1/microbiología , Biomarcadores/metabolismo , Bacterias/genética , Bacterias/metabolismo , MasculinoRESUMEN
Diabetes, a common chronic disease worldwide, can induce vascular complications, such as coronary heart disease (CHD), which is also one of the main causes of human death. It is of great significance to study the factors of diabetic patients complicated with CHD for understanding the occurrence of diabetes/CHD comorbidity. In this study, by analyzing the risk of CHD in more than 300,000 diabetes patients in southwest China, an artificial intelligence (AI) model was proposed to predict the risk of diabetes/CHD comorbidity. Firstly, we statistically analyzed the distribution of four types of features (basic demographic information, laboratory indicators, medical examination, and questionnaire) in comorbidities, and evaluated the predictive performance of three traditional machine learning methods (eXtreme Gradient Boosting, Random Forest, and Logistic regression). In addition, we have identified nine important features, including age, WHtR, BMI, stroke, smoking, chronic lung disease, drinking and MSP. Finally, the model produced an area under the receiver operating characteristic curve (AUC) of 0.701 on the test samples. These findings can provide personalized guidance for early CHD warning for diabetic populations.
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Enfermedad Coronaria , Diabetes Mellitus , Humanos , Inteligencia Artificial , Diabetes Mellitus/diagnóstico , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/etiología , China/epidemiología , Aprendizaje AutomáticoRESUMEN
Known to be involved in bone-cartilage metabolism, Vitamin D (VD) may play a role in human's disc pathophysiology. Given that postmenopausal women are prone to suffer VD deficiency and intervertebral disc degeneration (IDD), this study is intended to investigate whether VD can delay IDD in ovariectomized rats by improving bone microstructure and antioxidant stress. Female Sprague-Dawley rats were randomly allocated into four groups: sham, oophorectomy (OVX)+VD deficiency (VDD), OVX, and OVX+VD supplementation (VDS). In vivo, after a 6-month intervention, imaging and pathology slice examinations showed that IDD induced by OVX was significantly alleviated in VDS and deteriorated by VDD. The expressions of aggrecan and Collagen II in intervertebral disc were reduced by OVX and VDD, and elevated by VDS. Compared with the OVX+VDD and OVX group vertebrae, OVX+VDS group vertebrae showed significantly improved endplate porosity and lumbar bone mineral density with increased percent bone volume and trabecular thickness. Furthermore, 1α,25(OH)2D3 restored the redox balance (total antioxidant capacity, ratio of oxidized glutathione/glutathione) in the disc. The cocultivation of 1α,25(OH)2D3 and nucleus pulposus cells (NPCs) was conducted to observe its potential ability to resist excessive oxidative stress damage induced by H2O2. In vitro experiments revealed that 1α,25(OH)2D3 reduced the senescence, apoptosis, and extracellular matrix degradation induced by H2O2 in NPCs. In conclusion, VDS exhibits protective effects in OVX-induced IDD, partly by regulating the redox balance and preserving the microstructure of endplate. This finding provides a new idea for the prevention and treatment of IDD.
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Degeneración del Disco Intervertebral , Ovariectomía , Ratas Sprague-Dawley , Vitamina D , Animales , Femenino , Degeneración del Disco Intervertebral/prevención & control , Degeneración del Disco Intervertebral/metabolismo , Vitamina D/uso terapéutico , Vitamina D/farmacología , Densidad Ósea/efectos de los fármacos , Deficiencia de Vitamina D/complicaciones , Ratas , Agrecanos/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
Background: Intervertebral disc degeneration (IVDD), which contributes to stenosis of the spinal segment, commonly causes lower back pain. The process of IVDD degradation entails gradual structural adjustments accompanied by extreme transformations in metabolic homeostasis. However, the molecular and cellular mechanisms associated with IVDD are poorly understood. Methods: The RNA-sequencing datasets GSE34095 and GSE56081 were obtained from the Gene Expression Omnibus (GEO) database. Ferroptosis-related differentially expressed genes (DEGs) were identified from these gene sets. The protein-protein interaction (PPI) network was established and visualized using the STRING database and Cytoscape software, and the key functional modules of ferroptosis-related genes were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. Weighted gene co-expression network analysis (WGCNA), immune infiltration analysis in the GEO database, and other GSE series were used as validation datasets. The xCELL algorithm was performed to investigate the immune cell infiltration differences between the degenerated IVDD and control groups. Results: The major genes involved in nucleus pulposus tissue immune infiltration and ferroptosis-related genes were mined by bioinformatics analysis. A total of 3,056 DEGs were obtained between the IVDD tissue and control groups. The DEGs were enriched in the cell cycle; apoptosis; necroptosis; and the PI3K-Akt, Hippo, and HIF-1 signaling pathways. PCR and Western blot techniques were utilized to confirm the differential ferroptosis-related genes. The results indicated that the protein expression levels of NCOA4 and PCBP1 were elevated, while the protein expression level of GPX4 was reduced in NPCs following IL-1ß treatment. Our study has found that severe disc tissue degeneration leads to a noteworthy increase in the expression of CD8A in naive T cells, CCR7 in memory CD4+ cells, GZMB in natural killer (NK) cells, and CD163 and CD45 in macrophages. Conclusion: Our data demonstrate that ferroptosis occurs in IVDD, suggesting that ferroptosis may also increase IVDD improvement by triggering immune infiltration. This work was conducted to further understand IVDD pathogenesis and identify new treatment strategies.
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Intervertebral disk degeneration (IVDD) is the major cause of low back pain. Alpha-ketoglutaric acid (α-KG), an important intermediate in energy metabolism, has various functions, including epigenetic regulation, maintenance of redox homeostasis, and antiaging, but whether it can ameliorate IVDD has not been reported. Here, we examined the impacts of long-term administration of α-KG on aging-associated IVDD in adult rats. In vivo and in vitro experiments showed that α-KG supplementation effectively ameliorated IVDD in rats and the senescence of nucleus pulposus cells (NPCs). α-KG supplementation significantly attenuated senescence, apoptosis, and matrix metalloproteinase-13 (MMP-13) protein expression, and it increased the synthesis of aggrecan and collagen II in IL-1ß-treated NPCs. In addition, α-KG supplementation reduced the levels of IL-6, phosphorylated JAK2 and STAT3, and the nuclear translocation of p-STAT3 in IL-1ß-induced degenerating NPCs. The effects of α-KG were enhanced by AG490 in NPCs. The underlying mechanism may involve the inhibition of JAK2/STAT3 phosphorylation and the reduction of IL-6 expression. Our findings may help in the development of new therapeutic strategies for IVDD.NEW & NOTEWORTHY Alpha-ketoglutaric acid (α-KG) exerted its protective effect on nucleus pulposus cells' (NPCs) degeneration by inhibiting the senescence-associated secretory phenotype and extracellular matrix degradation. The possible mechanism may be associated with negatively regulating the JAK2/STAT3 phosphorylation and the decreased IL-6 expression, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK2/STAT3 pathway.
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Degeneración del Disco Intervertebral , Núcleo Pulposo , Animales , Ratas , Epigénesis Genética , Interleucina-6/metabolismo , Degeneración del Disco Intervertebral/tratamiento farmacológico , Ácidos Cetoglutáricos/farmacología , Núcleo Pulposo/metabolismoRESUMEN
To investigate the value of parameters of the pulmonary artery and right ventricular function in predicting the 30-day poor prognosis of patients with acute pulmonary embolism (APE). The heart rate, respiratory rate, systolic blood pressure, Wells score for APE, history of recent operation or immobilization, history of cancer, respiratory failure, smoking were significantly (Pâ <â .05) different among the control, good prognosis, and poor prognosis groups. The maximal short diameter of the right and left ventricle (RVD/LVD) ratio (Pâ <â .001) and left pulmonary artery (LPA) (Pâ =â .01) were significantly different between the good and poor prognosis groups. Systolic blood pressure (odds ratio [OR]: 0.98, Pâ =â .045) and the RVD/LVD ratio (OR: 12.57, Pâ =â .02) were significant independent risk factors for poor prognosis. The risk for poor prognosis significantly increased when the RVD/LVD ratio was >1.11 (cutoff value) with the area under the curve (AUC) of 0.71 (95% confidence interval [CI]: 0.61-0.80, Pâ <â .001). LPA (OR: 9.12, Pâ =â .01) and RVD/LVD (OR: 4.62, Pâ =â .012) were the significant independent risk factors for poor prognosis in the central pulmonary embolism. The LPA of 2.1 cm had the highest predictive value for poor prognosis in the central APE (AUC: 0.68; sensitivity 84.6%; specificity 53.1%). The RVD/LVD ratio and systolic blood pressure are significant risk factors for short-term prognosis in patients with APE. When the LPA isâ >2.1 cm in the central APE or the RVD/LVD isâ >1.11, the risk of poor prognosis increases, which can be used as important indicators for predicting the prognosis of patients with APE. Two hundred forty-three APE patients and 61 patients without APE who underwent computed tomographic pulmonary angiography (CTPA) were retrospectively enrolled as the experimental and the control group, respectively. APE patients who were followed up at the 30-day time point were divided into the good prognosis (nâ =â 195) and poor prognosis group (nâ =â 32). The main pulmonary artery (MPA) to the aorta (AO) ratio, maximal diameter of the LPA and right pulmonary artery (RPA), ratio of the RVD/LVD and the height and volume of the pulmonary artery (PAh and PAV, respectively) were analyzed after indexing to the body surface area.
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Hominidae , Embolia Pulmonar , Disfunción Ventricular Derecha , Humanos , Animales , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/etiología , Estudios Retrospectivos , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/complicaciones , Pronóstico , AngiografíaRESUMEN
Diabetes mellitus is a chronic metabolic disease, which causes an imbalance in blood glucose homeostasis and further leads to severe complications. With the increasing population of diabetes, there is an urgent need to develop drugs to treat diabetes. The development of artificial intelligence provides a powerful tool for accelerating the discovery of antidiabetic drugs. This work aims to establish a predictor called iPADD for discovering potential antidiabetic drugs. In the predictor, we used four kinds of molecular fingerprints and their combinations to encode the drugs and then adopted minimum-redundancy-maximum-relevance (mRMR) combined with an incremental feature selection strategy to screen optimal features. Based on the optimal feature subset, eight machine learning algorithms were applied to train models by using 5-fold cross-validation. The best model could produce an accuracy (Acc) of 0.983 with the area under the receiver operating characteristic curve (auROC) value of 0.989 on an independent test set. To further validate the performance of iPADD, we selected 65 natural products for case analysis, including 13 natural products in clinical trials as positive samples and 52 natural products as negative samples. Except for abscisic acid, our model can give correct prediction results. Molecular docking illustrated that quercetin and resveratrol stably bound with the diabetes target NR1I2. These results are consistent with the model prediction results of iPADD, indicating that the machine learning model has a strong generalization ability. The source code of iPADD is available at https://github.com/llllxw/iPADD.
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Inteligencia Artificial , Hipoglucemiantes , Hipoglucemiantes/farmacología , Simulación del Acoplamiento Molecular , Algoritmos , Aprendizaje AutomáticoRESUMEN
Selecting suitable promoters to drive gene overexpression can provide significant insight into the development of engineered bacteria. In this study, we analyzed the transcriptome data of Burkholderia pyrrocinia JK-SH007 and identified 54 highly expressed genes. The promoter sequences were located using genome-wide data and scored using the prokaryotic promoter prediction software BPROM to further screen out 18 promoter sequences. We also developed a promoter trap system based on two reporter proteins adapted for promoter optimization in B. pyrrocinia JK-SH007: firefly luciferase encoded by the luciferase gene set (Luc) and trimethoprim (TP)-resistant dihydrofolate reductase (TPr). Ultimately, eight constitutive promoters were successfully inserted into the probe vector and transformed into B. pyrrocinia JK-SH007. The transformants were successfully grown on Tp antibiotic plates, and firefly luciferase expression was determined by measuring the relative light unit (RLU). Five of the promoters (P4, P9, P10, P14, and P19) showed 1.01-2.51-fold higher activity than the control promoter λ phage transcriptional promoter (PRPL). The promoter activity was further validated via qPCR analysis, indicating that promoters P14 and P19 showed stable high transcription levels at all time points. Then, GFP and RFP proteins were overexpressed in JK-SH007. In addition, promoters P14 and P19 were successfully used to drive gene expression in Burkholderia multivorans WS-FJ9 and Escherichia coli S17-1. The two constitutive promoters can be used not only in B. pyrrocinia JK-SH007 itself to gene overexpression but also to expand the scope of application.
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Complejo Burkholderia cepacia , Luciferasas de Luciérnaga , Regiones Promotoras Genéticas , Genes ReporterosRESUMEN
INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.
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Antiulcerosos , Úlcera Duodenal , Humanos , Lansoprazol/efectos adversos , Úlcera Duodenal/tratamiento farmacológico , Úlcera Duodenal/inducido químicamente , Antiulcerosos/efectos adversos , Método Doble CiegoRESUMEN
This study investigated the correlation between 3-Tesla magnetic resonance imaging (MRI) and 256 multiple-slice computed tomography (MSCT) or 2-dimensional echocardiography (ECHO) in evaluating left ventricle. Forty patients were retrospectively enrolled to undergo cardiac MSCT, 3-Tesla MRI and 2-dimensional ECHO within 1 week. The end-diastolic (EDV) and end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) were analyzed and compared. MSCT was highly significantly correlated with MRI. Compared with MRI, MSCT slightly overestimated ESV for about 8.7 mL, but slightly underestimated EF and SV for about 6.8% and 5.8 mL, respectively. A high consistency existed between MSCT and MRI, with the 95% limit of agreement (-19.6, 25.4) mL for EDV, (-2.6,20.1) mL for ESV, (-28.3,16.6) mL for SV, and (-18.8%,5.1) % for EF. ECHO was also significantly correlated with MRI. The ECHO slightly underestimated the left ventricular function compared with MRI, with an underestimation of 9.4 mL for EDV, 3.5 mL for ESV, 5.8 mL for SV and 1.0% for EF. A wider agreement limit existed between MRI and ECHO. MSCT has a better correlation and agreement relationship with MRI parameters than 2-dimensional ECHO in assessing the left ventricle and may serve as a possible alternative to MRI.
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Ventrículos Cardíacos , Tomografía Computarizada por Rayos X , Humanos , Ventrículos Cardíacos/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética , Función Ventricular Izquierda , Volumen Sistólico , EcocardiografíaRESUMEN
PURPOSE: Quantitative measurement of pericoronary adipose tissue volume (PCATV) and fat attenuation index (FAI) has mostly been used in the study of coronary artery related diseases but rarely in the relationship with atrial fibrillation (AF). This study was conducted to investigate the correlation of PCATV and FAI with the AF recurrence after ablation and the clinical significance. MATERIALS AND METHODS: Patients with continuous AF who underwent radiofrequency ablation and computed tomographic angiography (CTA) were retrospectively enrolled. The PCATV, FAI, epicardial adipose tissue volume (EATV) and EAT density (EATD) arround the three main branches of the coronary arteries (LAD, LCX, and RCA) were measured quantitatively with cardiac function software and analyzed. RESULTS: 189 patients with continuous AF who underwent radiofrequency ablation for the first time were enrolled. After 12-month follow-up with a mean follow-up time of 10.93 ± 0.16 months, 47 (24.9%) patients were confirmed to have AF recurrence. The 3 V-FAI (- 81.17 ± 4.27 vs. - 83.31 ± 4.59 HU, P = 0.005), LCX-FAI (median - 77 vs. median - 81HU, P < 0.001), EATV (median 141.14vs. median 125.39 ml, P = 0.010), and EATVI (median 70.77 vs. 66.73 ml/m2, P = 0.008) were significantly increased in the recurrence group. EATVI (OR 1.043, 95% CI 1.020-1.066) and LCX-FAI (OR 1.254, 95% CI 1.145-1.374) were two significant independent risk factors for AF recurrence. In the comparison of ROC, the predictive value of LCX-FAI (cut-off value of >- 81.5 HU, area under the curve (AUC) of 0.722) was higher than that of EATVI (cut-off value > 81.07 ml/m2, AUC of 0.630). CONCLUSION: EATVI and LCX-FAI were related to recurrence of AF after ablation and have important clinical value in predicting the AF recurrence.
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Fibrilación Atrial , Ablación por Catéter , Enfermedad de la Arteria Coronaria , Humanos , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Fibrilación Atrial/etiología , Estudios Retrospectivos , Tejido Adiposo/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Angiografía por Tomografía Computarizada , Angiografía , Recurrencia , Ablación por Catéter/métodos , Angiografía CoronariaRESUMEN
BACKGROUND: Bismuth-containing quadruple therapy is an effective regimen for Helicobacter pylori (H. pylori) treatment. No head-to-head comparison trials have been conducted to evaluate the efficacy of colloidal bismuth pectin (CBP) in quadruple therapy for eradicating H. pylori. We aimed to compare the efficacy and safety of CBP quadruple therapy and bismuth potassium citrate (BPC) quadruple therapy for 14 days in the first-line treatment of H. pylori. METHODS: In this multicenter, randomized, double-blind, non-inferiority clinical trial, H. pylori-infected subjects without eradication history were randomized to receive amoxicillin 1 g twice daily, tetracycline 500 mg three time daily, esomeprazole 20 mg twice daily in combination with CBP 200 mg three time daily or BPC 240 mg twice daily for 14 days. 13 C-urea breath tests were used to access the eradication rate at least 4 weeks after treatment. RESULTS: Between April 2021 and July 2022, 406 patients were assessed for eligibility and 339 subjects were randomized. The cure rates (primary outcome) of CBP and BPC quadruple therapy were 90.5% and 92.3% (p = 0.56) by intention-to-treat analysis, respectively, and 96.1% and 96.2% (p = 1.00) by per-protocol analysis, respectively. CBP quadruple therapy was non-inferior to BPC quadruple therapy in the intention-to-treat and per-protocol analysis (p < 0.025). The frequency of adverse events and compliance were not different among the two groups (p > 0.05). CONCLUSIONS: Both CBP and BPC quadruple therapy for 14 days provide high efficacy, good compliance, and safety in the first-line treatment of H. pylori in China.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Bismuto/efectos adversos , Antibacterianos/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Quimioterapia Combinada , Amoxicilina/efectos adversos , Pectinas , Resultado del TratamientoRESUMEN
2'-O-methylation (2OM) is an omnipresent post-transcriptional modification in RNAs. It is important for the regulation of RNA stability, mRNA splicing and translation, as well as innate immunity. With the increase in publicly available 2OM data, several computational tools have been developed for the identification of 2OM sites in human RNA. Unfortunately, these tools suffer from the low discriminative power of redundant features, unreasonable dataset construction or overfitting. To address those issues, based on four types of 2OM (2OM-adenine (A), cytosine (C), guanine (G), and uracil (U)) data, we developed a two-step feature selection model to identify 2OM. For each type, the one-way analysis of variance (ANOVA) combined with mutual information (MI) was proposed to rank sequence features for obtaining the optimal feature subset. Subsequently, four predictors based on eXtreme Gradient Boosting (XGBoost) or support vector machine (SVM) were presented to identify the four types of 2OM sites. Finally, the proposed model could produce an overall accuracy of 84.3 % on the independent set. To provide a convenience for users, an online tool called i2OM was constructed and can be freely access at i2om.lin-group.cn. The predictor may provide a reference for the study of the 2OM.
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Biología Computacional , ARN , Humanos , ARN/genética , Metilación , Máquina de Vectores de Soporte , CitosinaRESUMEN
Studies have shown that serum response factor is beneficial for axonal regeneration of peripheral nerves. However, its role after central nervous system injury remains unclear. In this study, we established a rat model of T9-T10 spinal cord transection injury. We found that the expression of serum response factor in injured spinal cord gray matter neurons gradually increased with time, reached its peak on the 7th day, and then gradually decreased. To investigate the role of serum response factor, we used lentivirus vectors to overexpress and silence serum response factor in spinal cord tissue. We found that overexpression of serum response factor promoted motor function recovery in rats with spinal cord injury. Qualitative observation of biotinylated dextran amine anterograde tracing showed that overexpression of serum response factor increased nerve fibers in the injured spinal cord. Additionally, transmission electron microscopy showed that axon and myelin sheath morphology was restored. Silencing serum response factor had the opposite effects of overexpression. These findings suggest that serum response factor plays a role in the recovery of motor function after spinal cord injury. The underlying mechanism may be related to the regulation of axonal regeneration.
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PURPOSE: To investigate the relationship between filling defects in the left atrial appendage restricted to the early phase of cardiac computed tomography (CCT), and ischemic stroke in patients with atrial fibrillation (AF). MATERIALS AND METHODS: A total of 152 patients with non-valvular AF were retrospectively enrolled and divided into two groups according to the stroke history, as confirmed by brain computed tomography (CT) or magnetic resonance imaging (MRI), as the non-stroke group (n = 89) and stroke group (n = 63), respectively. The numbers of patients with filling defects in the early phase of CCT images without thrombi were recorded. Morphological parameters of the LAA were measured for all participants. All patients with early-phase filling defects (n = 44) were assigned to two groups according to ischemic stroke history: the filling defects with stroke group (n = 28) and the filling defects without stroke group (n = 16). The clinical characteristics and LAA morphological parameters were compared. RESULTS: Univariate analysis showed that compared with the non-stroke groupï¼LAA volume index and age were higher in the stroke group, and the ratio of early phase filling defect in LAA, hypertension and diabetes were also higher, in the meanwhile the LVEF and BMI were lower (P < 0.05).After adjusting confounding factors by the multivariate logistic regression analysis, filling defect was significantly related with stroke [odds ratio (OR): 4.339, 95% confidence interval (CI): 1.951-9.653, P = 0.000]. LAA morphological parameters were not significantly different between the filling defects with stroke group and the group without stroke. CONCLUSION: AF patients with LAA non-thrombotic filling defects in the early-phase of CCT had an increased risk of ischemic stroke compared to those without filling defects. This finding may help to optimize stroke risk stratification in patients with AF.
Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Trombosis , Humanos , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/complicaciones , Apéndice Atrial/diagnóstico por imagen , Estudios Retrospectivos , Accidente Cerebrovascular/etiología , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Tomografía Computarizada Multidetector/métodos , Trombosis/etiología , Ecocardiografía Transesofágica/efectos adversosRESUMEN
Background: The significance of left atrial appendage (LAA) filling defects on early-phase cardiac computed tomography (CCT) remains uncertain. This study retrospectively investigated predictive factors of LAA filling defects on early-phase CCT. Methods: A total of 68 patients with nonvalvular atrial fibrillation (AF) and early filling defect on CCT who underwent transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were enrolled [48 males, 20 females; mean ± standard deviation (SD) age 62.72±8.13 years]. Additionally 68 sex- and age-matched patients with normal LAA filling were included as the control group. CCT, ultrasound, clinical and laboratory data were analyzed. Baseline data between groups were analyzed using t-, Mann-Whitney, and chi-squared tests. Multivariable logistic regression analysis was used to adjust for confounders. Pearson correlation analysis was used to confirm correlations between variables. Results: Decreased LAA flow velocity [LAAFV; odds ratio (OR) =0.918; 95% confidence interval (CI): 0.883-0.954; P<0.001] and increased left atrial volume index (LAVI; OR =1.055; 95% CI: 1.012-1.099; P=0.011) were significantly associated with early-phase CCT LAA filling defects. The LAAFV threshold for predicting early LAA filling defects was 40.5 cm/s, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.905 (sensitivity 82.4%, specificity 91.2%); the LAVI predictive threshold was 58.77 mL/m2 (AUC =0.840, sensitivity 85.3%, specificity 72.1%). A significant positive correlation was detected between LAAFV and the Hounsfield unit (HU) ratio of the LAA to ascending aorta on early-phase CCT (r=0.614; P<0.001), as well as the HU difference in LAA between early and delayed phase CCT (r=0.591; P<0.001). There were significant (P<0.05) differences in LAAFV between different filling defects. Conclusions: Decreased LAAFV and increased LAVI are independent factors associated with LAA filling defects only on early-phase CCT. Early-phase CCT LAA filling defect is associated with LAA emptying dysfunction. These findings contribute to thrombosis risk stratification in patients with AF.