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1.
Iran J Sci Technol Trans A Sci ; : 1-9, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34803335

RESUMO

To investigate the characteristic findings between laboratory-confirmed and clinically suspected patients with COVID-19. In this retrospective study, we included patients admitted to the Xiangya Hospital from Jan 24 to Feb 10, 2020. Two researchers separately collected and sorted out the patients' epidemiological, demographic, clinical, laboratory, and radiologic findings. SPSS was performed to analyze the collected data. 241 patients were admitted, including 28 (45.5; IQR, 34.0-52.5) confirmed and 213 (42.0; IQR, 30.0-57.0) suspected patients. The prevalence of COVID-19 disease in males was significantly higher than in females (64.3% vs. 35.7%, P = 0.033). Before admission of the confirmed and suspected undiagnosed cases, the onset of symptoms is often manifested as respiratory symptoms such as fever (35.7% vs. 27.7%) and cough (30.7% vs. 32.1%). Twenty patients (71.4%) had an exposure history to high-risk areas, and 14 patients (50.0%) traveled or lived in a high-risk area in the confirmed group, which was significantly different from the suspected group. The pulmonary imaging of the patients in the confirmed group was primarily manifested as ground-glass opacity (89.3%). A total of 499 nucleic acid testing (NAT) was performed to determine the 28 COVID-19 positive throat swabs among the 241 patients. Whether there is a history of high-risk area exposure in the epidemiological investigation is essential in distinguishing the suspected patients from the confirmed patients. Multiple nucleic acid tests were used as the basis for the diagnosis of COVID-19, and during CT examination, ground-glass opacity was used as a COVID-19 indicator. Trail registration Trail registration number. 202012195, Date of registration: 2020.12.22 "retrospectively registered".

2.
BMJ Open ; 11(11): e049807, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785549

RESUMO

OBJECTIVE: To clarify high-risk factors for adverse pregnancy outcomes (APOs) in systemic lupus erythaematosus (SLE). DESIGN: A retrospective chart review study. SETTING: Data were collected in a tertiary medical centre, Shanghai, China, from November 2010 to December 2018. PARTICIPANTS: A total of 513 pregnancies with SLE were retrospectively analysed. Twenty-seven patients who underwent artificial abortions due to personal reasons were excluded. PRIMARY OUTCOME MEASURES: APOs were primary outcomes, including foetal loss, premature birth, small for gestational age (SGA), asphyxia neonatorum, composite foetal APOs and hypertensive disorders of pregnancy (HDP). Multivariable logistic regression and Spearman correlation analysis were performed to determine the risk factors for APOs in SLE. RESULTS: Risk factors for foetal loss included prepregnancy hypertension, hypocomplementaemia-C3, anticardiolipin antibodies-IgM positivity and disease flares during pregnancy. Risk factors for premature birth included disease flares, use of immunosuppressive agents and HDP. Moreover, twin pregnancy, disease flares and HDP were risk factors for SGA, and prepregnancy hypertension was an independent risk factor for asphyxia neonatorum. Independent risk factors for composite foetal APOs included twin pregnancy, prepregnancy hypertension, disease flares during pregnancy, HDP, hypocomplementaemia-C3 and the use of immunosuppressive agents. Risk factors for SLE complicated with HDP included prepregnancy hypertension, renal disorders and thrombocytopaenia. Conversely, the use of aspirin was a protective factor against foetal loss and premature birth. The ds-DNA value had a low diagnostic value for APOs, whereas the extent of complement reduction may predict the incidence of composite foetal APOs and foetal loss. Proteinuria occurring in the first 20 gestational weeks may lead to APOs. CONCLUSION: Established risk factors for each APO were identified in this study. Indicators with more predictive significance have been screened out from conventional indicators, which may help clinicians predict the pregnancy outcome of patients with SLE more accurately and minimise the incidence of APOs.

3.
World J Pediatr ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738199

RESUMO

BACKGROUND: Fragile X syndrome (FXS), caused by CGG-repeat expansion in FMR1 promoter, is one of the most common causes of mental retardation. Individuals with full mutation and premutation alleles have a high risk of psychophysiological disorder and of having affected offspring. Frequencies of FMR1 alleles in general newborns have been reported in Caucasians but have not been investigated in the large-scale population in  the mainland of China. METHODS: The sizes of FMR1 CGG-repeats were analyzed in 51,661 newborns (28,114 males and 23,547 females) and also in a cohort of 33 children diagnosed with developmental delay using GC-rich polymerase chain reaction (PCR) and triple repeat primed PCR. RESULTS: The frequency of CGG repeats > 100 was 1/9371 in males and 1/5887 in females, and the frequency of CGG repeats > 54 was 1/1561 in males and 1/1624 in females. FMR1 full mutation and premutation were identified in 27.27% of children who had Ages and Stages Questionnaire scores less than two standard deviations from the cutoff value. CONCLUSIONS: Our study revealed the prevalence of FXS in China and improved the sample databases of FXS, suggesting that the prevalence of FXS in Chinese is higher than estimated previously and that FXS screening can be advised to high-risk families.

4.
Front Endocrinol (Lausanne) ; 12: 713192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744998

RESUMO

Background: Hypoglycemia is an important event that could be related to increased mortality in patients with diabetes. The risk of hypoglycemia is not clearly illustrated to increase when Sodiumglucose co-transporter 2 (SGLT-2) inhibitors are used concomitantly with sulfonylureas. The present study will assess the risk of hypoglycemia associated with the concomitant use of SGLT-2 inhibitors and sulfonylureas compared with placebo and sulfonylureas. Method: We searched Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov and identified the randomized trials comparing SGLT-2 inhibitors with placebo for type 2 diabetes treated with sulfonylureas. The risk of bias in each trial was assessed using the Cochrane tool. The risk ratio of hypoglycemia was measured using the Mantel Haenszel method. We also performed subgroup analysis to examine the dosage effects. The number needed to harm (NNH) was measured according to the duration of intervention. Results: A total of 12 studies, including 3761 participants, were enrolled in our systematic review and meta-analysis. The risk ratio of hypoglycemia was 1.67 (95% CI 1.42 to 1.97). The NNH was 13 (95% CI 9 to 21) for a treatment duration of 24 weeks or less, 11 (8 to 18) for 25 to 48 weeks, and 7 (5 to 10) for more than 48 weeks. Subgroup analysis showed that no difference was found between higher and lower doses of SGLT-2 inhibitors. The risk ratio related to lower dose SGLT-2 inhibitors was 1.56 (95% CI 1.30 to 1.88), and the risk ratio related to higher dose SGLT-2 inhibitors was 1.70 (95% CI 1.42 to 2.04). Conclusions: The risk of hypoglycemia was significantly increased in subjects treated with SGLT-2 inhibitors compared with placebo. Addition of SGLT-2 inhibitors to sulfonylureas would lead to one more case of hypoglycemia in every 13 patients with a treatment duration less than 24 weeks. This suggests that a decrease in sulfonylureas dose may be an important recommendation when adding SGLT-2 inhibitors to sulfonylureas.

5.
Front Oncol ; 11: 737497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745958

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumor in the world and its incidence is increasing in many countries. In recent years, with the deepening understanding of the immune and pathological mechanisms of HCC, immunotherapy based on the regulation of tumor immune microenvironment has become a new treatment choice for patients with HCC. Immune checkpoint inhibitors (ICIs) targeting programmed death protein-1, programmed death protein-ligand-1, or cytotoxic T-lymphocyte-associated antigen 4 are the most widely used. Instead of general immune-enhancing therapies, ICIs can reactivate anti-tumor immune responses by disrupting co-inhibitory T cell signaling. In this review, the research progress and existing problems of ICIs in the treatment of HCC in recent years are reviewed.

6.
Org Lett ; 23(20): 7910-7915, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34605653

RESUMO

A Pd(II)-catalyzed enantioselective C-H alkynylation of 2-(arylsulfinyl)pyridines via kinetic resolution using cheap and commercially available l-pGlu-OH as a chiral ligand is reported. A wide range of 2-(arylsulfinyl)pyridines were compatible with this protocol, giving the alkynylation products and recovered sulfoxides in high yields with high enantioselectivities (up to 99% ee). Furthermore, the enantioenriched products can be easily transformed to several other types of chiral sulfoxide scaffolds with the retention of enantiopurity.

7.
Front Plant Sci ; 12: 727596, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646287

RESUMO

With increasing areas of direct sowing, low-temperature (LT) stress drastically affects global rice production. Exogenous applications of melatonin (MT) serve as one of the effective ways to improve seed germination under various stress conditions. In this study, we found that MT treatment greatly improved the LT stress-induced loss of germination percentage and the weak performance of seedlings under LT of constant 20°C (LT20). This was largely dependent on the activated antioxidant system and enhanced activities of storage substance utilization-associated enzymes. Moreover, we also detected that exogenous feeding of MT significantly increased the biosynthesis of gibberellin (GA) and endogenous MT but simultaneously inhibited the accumulation of abscisic acid (ABA) and hydrogen peroxide (H2O2) under LT20 stress. These results suggested that MT had antagonistic effects on ABA and H2O2. In addition, MT treatment also significantly enhanced the expression of CATALYSE 2 (OsCAT2), which was directly regulated by ABA-INSENSITIVE 5 (OsABI5), a core module of ABA-stressed signals, and thus promoting the H2O2 scavenging to reach reactive oxygen species (ROS) homeostasis, which consequently increased GA biosynthesis. However, in abi5 mutants, OsCAT2 failed in response to LT20 stress irrespective of MT treatment, indicating that OsABI5 is essential for MT-mediated seed germination under LT20 stress. Collectively, we now demonstrated that MT showed a synergistic interaction with an ABI5-mediated signal to mediate seed germination, partially through the direct regulation of OsCAT2.

8.
Eur Radiol ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34671832

RESUMO

OBJECTIVES: To develop and validate an ultrasound elastography radiomics nomogram for preoperative evaluation of the axillary lymph node (ALN) burden in early-stage breast cancer. METHODS: Data of 303 patients from hospital #1 (training cohort) and 130 cases from hospital #2 (external validation cohort) between Jun 2016 and May 2019 were enrolled. Radiomics features were extracted from shear-wave elastography (SWE) and corresponding B-mode ultrasound (BMUS) images. The minimum redundancy maximum relevance and least absolute shrinkage and selection operator algorithms were used to select ALN status-related features. Proportional odds ordinal logistic regression was performed using the radiomics signature together with clinical data, and an ordinal nomogram was subsequently developed. We evaluated its performance using C-index and calibration. RESULTS: SWE signature, US-reported LN status, and molecular subtype were independent risk factors associated with ALN status. The nomogram based on these variables showed good discrimination in the training (overall C-index: 0.842; 95%CI, 0.773-0.879) and the validation set (overall C-index: 0.822; 95%CI, 0.765-0.838). For discriminating between disease-free axilla (N0) and any axillary metastasis (N + (≥ 1)), it achieved a C-index of 0.845 (95%CI, 0.777-0.914) for the training cohort and 0.817 (95%CI, 0.769-0.865) for the validation cohort. The tool could also discriminate between low (N + (1-2)) and heavy metastatic ALN burden (N + (≥ 3)), with a C-index of 0.827 (95%CI, 0.742-0.913) in the training cohort and 0.810 (95%CI, 0.755-0.864) in the validation cohort. CONCLUSION: The radiomics model shows favourable predictive ability for ALN staging in patients with early-stage breast cancer, which could provide incremental information for decision-making. KEY POINTS: • Radiomics analysis helps radiologists to evaluate the axillary lymph node status of breast cancer with accuracy. • This multicentre retrospective study showed that radiomics nomogram based on shear-wave elastography provides incremental information for risk stratification. • Treatment can be given with more precision based on the model.

9.
Mol Med Rep ; 24(6)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34676879

RESUMO

Intervertebral disc degeneration (IDD) is a major cause of lower back pain. The high morbidity associated with this disease diminishes the quality of life of those who are affected. MicroRNAs (miRs) play crucial roles in various diseases, including IDD. However, the mechanism via which miR­200c­3p plays a role in the development of IDD remains unknown. The present study aimed to investigate the effect of miR­200c­3p on the progression of IDD and the underlying mechanism. The expression level of miR­200c­3p was evaluated in intervertebral disc tissues from patients with IDD. To construct the IDD cell model, the nucleus pulposus (NP) cells were treated with lipopolysaccharide (LPS) 24 h following transfection with miR­200c­3p mimic or inhibitor. A luciferase activity assay was performed, while reverse transcription­quantitative PCR and western blotting were conducted to determine the RNA and protein expression levels, respectively. The expression level of miR­200c­3p in the intervertebral disc tissues of patients with IDD was lower than that of normal subjects. LPS treatment reduced the expression level of miR­200c­3p in NP cells. Moreover, miR­200c­3p mimic inhibited LPS­induced NP cell apoptosis. It was found that miR­200c­3p attenuated inflammatory cytokine levels and extracellular matrix (ECM) degradation in NP cells. Furthermore, miR­200c­3p targeted Ras­related protein 2C (RAP2C) in NP cells. RAP2C promoted apoptosis, inflammatory cytokine levels and ECM degradation by activating ERK signaling. Knockdown of RAP2C and inhibition of ERK signaling by SCH772984 partially reversed the proinflammatory effect of the miR­200c­3p inhibitor on LPS­treated NP cells. Thus, miR­200c­3p inhibits NP cell apoptosis, inflammatory cytokine levels and ECM degradation in IDD by targeting RAP2C/ERK signaling.

10.
Front Big Data ; 4: 699070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34514380

RESUMO

To improve consumer engagement and satisfaction, online news services employ strategies for personalizing and recommending articles to their users based on their interests. In addition to news agencies' own digital platforms, they also leverage social media to reach out to a broad user base. These engagement efforts are often disconnected with each other, but present a compelling opportunity to incorporate engagement data from social media to inform their digital news platform and vice-versa, leading to a more personalized experience for users. While this idea seems intuitive, there are several challenges due to the disparate nature of the two sources. In this paper, we propose a model to build a generalized graph of news articles and tweets that can be used for different downstream tasks such as identifying sentiment, trending topics, and misinformation, as well as sharing relevant articles on social media in a timely fashion. We evaluate our framework on a downstream task of identifying related pairs of news articles and tweets with promising results. The content unification problem addressed by our model is not unique to the domain of news, and thus can be applicable to other problems linking different content platforms.

11.
IUBMB Life ; 73(12): 1406-1422, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34590407

RESUMO

Deficiency of G protein-coupled receptor kinase 2 (GRK2) was found to protect mice from dextran sulfate sodium (DSS)-induced colitis. Paeoniflorin-6'-O-benzene sulfonate (CP-25) has been shown to exert anti-inflammatory immune regulatory effects in animal models of inflammatory autoimmune disease. This study aimed to investigate the of GRK2 in the pathogenesis of ulcerative colitis (UC) and its effects on macrophage polarization, macrophage subtype regulation of intestinal barrier function, and therapeutic effects of CP-25 in mice with DSS-induced colitis. We found imbalanced macrophage polarization, intestinal barrier dysfunction, and abnormal activation of GRK2 and TLR4-NF-κB-NLRP3 inflammasome signaling pathway in the colonic mucosa of patients with UC. CP-25, restored the damaged intestinal barrier function by inhibiting the transmembrane region of GRK2 in macrophages stimulated by lipopolysaccharides. CP-25 exerted therapeutic effects by ameliorating clinical manifestation, regulating macrophage polarization, and restoring abnormally activated TLR4-NF-κB-NLRP3 inflammasome signaling pathway by inhibiting GRK2. These data suggest the pathogenesis of UC may be related to the imbalance of macrophage polarization, which leads to abnormal activation of TLR4-NF-κB-NLRP3 inflammasome signaling pathway mediated by GRK2 and destruction of the intestinal mucosal barrier. CP-25 confers therapeutic effects on colitis by inhibiting GRK2 translocation to induce the downregulation of TLR4-NF-κB-NLRP3 inflammasome signaling in macrophages.

12.
J Cancer ; 12(17): 5206-5219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335937

RESUMO

Circular RNAs (circRNAs) are a unique family of noncoding RNAs that could regulate multiple biological processes, which play a crucial role in carcinogenesis, progression and chemotherapy resistance of cancers. Growing studies have demonstrated that circRNAs act as novel biomarkers and therapeutic targets for cancers by sponging microRNAs (miRNAs). Up to date, another function of circRNAs, combining with RNA-binding proteins (RBPs), was uncovered. However, there is limit studies illustrating the underlying mechanism of circRNAs-RBPs interactions, as well as showing its roles in diverse types of cancers. In this review, we collected the biogenesis, properties of circRNAs, and then synthesize the connection between circRNAs and RBPs, and try to clarify its molecular mechanisms involving in the pathogenesis and progression of several common cancers, aiming to provide a brand-new insight to the prognosis and treatment strategy for cancers.

13.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3487-3493, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402270

RESUMO

Nano-LC-MS/MS was used to analyze trypsin digested deer-horn gelatin( DCG) and deer-hide gelatin( DHG) samples.The glycopeptides in DCG and DHG were quantified by Label-free quantitative( LFQ) peptidomics,on the basis of which the glycopeptides with significant difference in DCG and DHG were determined. As a result,5 736 peptides were identified from DCG samples,including 213 galactosyl-hydroxylysine containing peptides( Gal-Hyl-peptides) and 102 glucosyl-galactosyl-hydroxylysine containing peptides( Glc-Gal-Hyl-peptides),while 6 836 peptides were identified from DHG samples,among which there were 250 Gal-Hyl-peptides and 98 Glc-Gal-Hyl-peptides. With over 3-fold peak area difference and highly significant intergroup difference( P < 0. 01) as the screening criteria,444 differential peptides were determined in DCG and DHG,including 16 Gal-Hyl-peptides and 5 Glc-Gal-Hyl-peptides. Then XIC peak shapes,standard deviation of peak area,and fold change were applied for further screening and 5 glycopeptides with significant differences in DCG and DHG were confirmed,which could serve as potential biomarkers for distinguishing DCG and DHG. The present study provided ideas and strategies for the in-depth investigation on the discrimination of DCG and DHG and is of good theoretical significance and application value for the further research on chemical constituents and quality control of gelatin derived Chinese medicinals.


Assuntos
Cervos , Gelatina , Animais , Cromatografia Líquida , Glicopeptídeos , Espectrometria de Massas em Tandem
14.
Bioelectrochemistry ; 142: 107928, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34428614

RESUMO

Prostate cancer is one of the most common cancers in the world, and its early detection is vital to saving the lives of patients. In this research, a novel label-free photoelectrochemical immunosensor was designed for sensitive detection of prostate specific antigen (PSA). Ag2S sensitized on Ag/AgBr/BiOBr heterojunction could effectively inhibit photogenic holes recombination and improve photocurrent response and sensitivity. Ascorbic acid was an effective electron donor, which can effectively eliminate photo-generated holes. The photocurrent reduced linearly with the logarithm of PSA concentration ranged from 0.001 to 50 ng·mL-1 and the limit of detection was 0.25 pg·mL-1. The designed sensor had the advantages of wide linear range, good stability, high reproducibility, and good selectivity. This study not only provided a method for efficient and sensitive detection of PSA, but also provided valuable reference ideas for the detection of other tumor markers.

15.
BMC Gastroenterol ; 21(1): 332, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433418

RESUMO

BACKGROUND: Acute pancreatitis is a common and potentially lethal gastrointestinal disease, but literatures for the disease burden are scarce for many countries. Understanding the current burden of acute pancreatitis and the different trends across various countries is essential for formulating effective preventive intervenes. We aimed to report the incidence, mortality, and disability-adjusted life-years (DALYs) caused by acute pancreatitis in 204 countries and territories between 1990 and 2019. METHODS: Estimates from the Global Burden of Disease Study 2019 (GBD 2019) were used to analyze the epidemiology of acute pancreatitis at the global, regional, and national levels. We also reported the correlation between development status and acute pancreatitis' age-standardized DALY rates, and calculated DALYs attributable to alcohol etiology that had evidence of causation with acute pancreatitis. All of the estimates were shown as counts and age-standardized rates per 100,000 person-years. RESULTS: There were 2,814,972.3 (95% UI 2,414,361.3-3,293,591.8) incident cases of acute pancreatitis occurred in 2019 globally; 1,273,955.2 (1,098,304.6-1,478,594.1) in women and 1,541,017.1 (1,307,264.4-1,814,454.3) in men. The global age-standardized incidence rate declined from 37.9/100,000 to 34.8/100,000 during 1990-2019, an annual decrease of 8.4% (5.9-10.4%). In 2019, there were 115,053.2 (104,304.4-128,173.4) deaths and 3,641,105.7 (3,282,952.5-4,026,948.1) DALYs due to acute pancreatitis. The global age-standardized mortality rate decreased by 17.2% (6.6-27.1%) annually from 1.7/100,000 in 1990 to 1.4/100,000 in 2019; over the same period, the age-standardized DALY rate declined by 17.6% (7.8-27.0%) annually. There were substantial differences in the incidence, mortality and DALYs across regions. Alcohol etiology attributed to a sizable fraction of acute pancreatitis-related deaths, especially in the high and high-middle SDI regions. CONCLUSION: Substantial variation existed in the burden of acute pancreatitis worldwide, and the overall burden remains high with aging population. Geographically targeted considerations are needed to tailor future intervenes to relieve the burden of acute pancreatitis in specific countries, especially for Eastern Europe.


Assuntos
Saúde Global , Pancreatite , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Carga Global da Doença , Humanos , Incidência , Masculino , Pancreatite/epidemiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-34460385

RESUMO

Detecting anomalies on graph data has two types of methods. One is pattern mining that discovers strange structures globally such as quasi-cliques, bipartite cores, or dense blocks in the graph's adjacency matrix. The other is feature learning that mainly uses graph neural networks (GNNs) to aggregate information from local neighborhood into node representations. However, there is a lack of study that utilizes both the global and local information for graph anomaly detection. In this article, we propose a synergistic approach that leverages pattern mining to inform the GNN algorithms on how to aggregate local information through connections to capture the global patterns. Specifically, it uses a GNN encoder to perform feature aggregation, and the pattern mining algorithms supervise the GNN training process through a novel loss function. We provide theoretical analysis on the effectiveness of the loss function, as well as empirical analysis on the proposed approach across a variety of GNN algorithms and pattern mining methods. Experiments on real-world data show that the synergistic approach performs significantly better than existing graph anomaly detection methods.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34461299

RESUMO

BACKGROUND & AIMS: Cirrhotic cardiomyopathy is a major complication and cause of morbidity in end-stage primary biliary cholangitis (PBC). However, it is unclear whether there is clinically silent myocardial involvement at the early stage of PBC before cirrhosis and cardiac manifestations. This prospective, three-center, multi-modality cardiac imaging study on the early identification of myocardial impairment in PBC (EARLY-MYO-PBC) was designed to identify silent myocardial impairment in PBC patients without cardiac manifestations. METHODS: A total of 112 subjects (56 with PBC and 56 age- and sex-matched controls) undergoing cardiovascular magnetic resonance (CMR) were enrolled. Demographic, serologic, and cardiac imaging data were prospectively collected. All participants had no cardiac discomfort or previous heart disease and had normal electrocardiographic findings. RESULTS: Subclinical myocardial involvement, as evidenced by cardiac morphologic, functional, and tissue characterization changes on CMR, including hyperdynamic left ventricular (LV) ejection fraction (median, 75% in PBC patients vs 69% in controls, P = .029), subclinical myocardial edema by T2-short tau inversion recovery (21% vs 2% in controls, P = .001), elevated extracellular matrix indices (30% vs 26% in controls, P < .001), and impaired myocardial viability by positive late gadolinium enhancement (LGE) (36%), was detected in PBC patients. Importantly, a mid-wall "stripe" at the LV septum was identified as a PBC-specific LGE pattern that differs from other known cardiomyopathies. In multivariate analysis, gp210 positivity (odds ratio [OR] = 9.909, P = .010), lower hemoglobin (OR = 0.919, P = .004), and body mass index (OR = 0.638, P = .005) were independent predictors of cardiac abnormalities in PBC. CONCLUSIONS: This study demonstrates clinically silent cardiac impairment with specific CMR patterns in PBC, allowing optimal screening for early myocardial impairment and potentially timely therapies. (Trial registration no.: NCT03545672).

18.
Sci Rep ; 11(1): 15610, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341433

RESUMO

As a highly prevalent disease among women worldwide, breast cancer remains in urgent need of further elucidation its molecular mechanisms to improve the patient outcomes. Identifying hub genes involved in the pathogenesis and progression of breast cancer can potentially help to unveil mechanism and also provide novel diagnostic and prognostic markers. In this study, we integrated multiple bioinformatic methods and RNA in situ detection technology to identify and validate hub genes. EZH2 was recognized as a key gene by PPI network analysis. CENPL, ISG20L2, LSM4, MRPL3 were identified as four novel hub genes through the WGCNA analysis and literate search. Among these, many studies on EZH2 in breast cancer have been reported, but no studies are related to the roles of CENPL, ISG20L2, MRPL3 and LSM4 in breast cancer. These four novel hub genes were up-regulated in tumor tissues and associated with cancer progression. The receiver operating characteristic analysis and Kaplan-Meier survival analysis indicated that these four hub genes are promising candidate genes that can serve as diagnostic and prognostic biomarkers for breast cancer. Moreover, these four newly identified hub genes as aberrant molecules in the maintenance of breast cancer development, their exact functional mechanisms deserve further in-depth study.


Assuntos
Neoplasias da Mama , Biomarcadores Tumorais/genética , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Prognóstico
19.
Int J Mol Sci ; 22(14)2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34299293

RESUMO

Brassinosteroids (BRs) are growth-promoting phytohormones that can efficiently function by exogenous application at micromolar concentrations or by endogenous fine-tuning of BR-related gene expression, thus, precisely controlling BR signal strength is a key factor in exploring the agricultural potential of BRs. BRASSINOSTEROID INSENSITIVE1 (BRI1), a BR receptor, is the rate-limiting enzyme in BR signal transduction, and the phosphorylation of each phosphorylation site of SlBRI1 has a distinct effect on BR signal strength and botanic characteristics. We recently demonstrated that modifying the phosphorylation sites of tomato SlBRI1 could improve the agronomic traits of tomato to different extents; however, the associated agronomic potential of SlBRI1 phosphorylation sites in tomato has not been fully exploited. In this research, the biological functions of the phosphorylation site threonine-825 (Thr-825) of SlBRI1 in tomato were investigated. Phenotypic analysis showed that, compared with a tomato line harboring SlBRI1, transgenic tomato lines expressing SlBRI1 with a nonphosphorylated Thr-825 (T825A) exhibited a larger plant size due to a larger cell size and higher yield, including a greater plant height, thicker stems, longer internodal lengths, greater plant expansion, a heavier fruit weight, and larger fruits. Molecular analyses further indicated that the autophosphorylation level of SlBRI1, BR signaling, and gibberellic acid (GA) signaling were elevated when SlBRI1 was dephosphorylated at Thr-825. Taken together, the results demonstrated that dephosphorylation of Thr-825 can enhance the functions of SlBRI1 in BR signaling, which subsequently activates and cooperates with GA signaling to stimulate cell elongation and then leads to larger plants and higher yields per plant. These results also highlight the agricultural potential of SlBRI1 phosphorylation sites for breeding high-yielding tomato varieties through precise control of BR signaling.


Assuntos
Brassinosteroides/metabolismo , Lycopersicon esculentum/genética , Proteínas Serina-Treonina Quinases/genética , Tamanho Celular , Frutas/metabolismo , Lycopersicon esculentum/crescimento & desenvolvimento , Lycopersicon esculentum/metabolismo , Fosforilação , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/genética , Treonina/metabolismo
20.
Int J Clin Pharmacol Ther ; 59(10): 674-683, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34308834

RESUMO

OBJECTIVE: The present study evaluated the bioequivalence of the test preparation (5 mg generic solifenacin succinate tablet, produced by Jiangsu Deyuan Pharmaceutical Co., Ltd.) or the reference preparation (5 mg solifenacin succinate tablets with the trade name Vesicare, produced by Astellas Pharma Europe B.V.) in either fasting or postprandial states in healthy Chinese subjects. MATERIALS AND METHODS: The present study was designed as an open-label, randomized, single-center, single-dose, dual-cycle, dual-crossover, fasting/postprandial study. 56 healthy Chinese subjects (28 each in the fasting and postprandial groups) were enrolled. WinNolin software (version 7.0 or above) was used to calculate the pharmacokinetic parameters. RESULTS: In the fasting and postprandial group, pharmacokinetic analysis and bioequivalence analysis were carried out based on the blood concentration-time data. The 90% confidence interval of the geometric mean ratio of Cmax, AUC0-t, and AUC0-∞ of the test preparation and the reference preparation were both within the acceptance range of 80.00 - 125.00%. CONCLUSION: A single administration of a 5-mg tablet of either the test preparation, generic solifenacin succinate, or the reference preparation, solifenacin succinate with the brand-name Vesicare, was safe and bioequivalent in healthy Chinese subjects in either fasting or postprandial states according to the criteria of bioequivalence of the State Drug Administration of China.


Assuntos
Jejum , Succinato de Solifenacina , Adulto , Área Sob a Curva , China , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Comprimidos , Equivalência Terapêutica
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