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1.
J Chem Inf Model ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33190499

RESUMO

Ligand-similarity-based virtual screening is one of the most applicable computer-aided drug design techniques. The current methodology relies heavily on several descriptors of molecular features, including atoms (zero-dimensional, 0D), the presence or absence of structural features (one-dimensional, 1D), topological descriptors (two-dimensional, 2D), geometry and volume (three-dimensional, 3D), or stereoelectronic and stereodynamic properties (four-dimensional, 4D). These descriptors have been frequently used in virtual screening; however, they are usually used independently without integration, which may hinder effective and precise virtual screening. In this study, we developed a multifeature integration algorithm named LigMate, which employs a Hungarian algorithm-based matching and a machine learning-based nonlinear combination of various descriptors, including the new relevant descriptors focusing on the maximum common substructures (maximum common substructure score, MCSS), the relative distance of atoms from the ligand mass center (intraligand distance score, ILDS), as well as the ring differences (ring score, RS). In the benchmark tests, LigMate achieved an overall enrichment factor of the first percent (EF1) of 36.14 and an area under the curve (AUC) value of 0.81 on the DUD-E data set, as well as an EF1 of 15.44 and an AUC of 0.69 on the maximum unbiased validation (MUV) data set, outperforming the control methods that are based on single descriptors. Thus, our study provides a new framework for multiple feature integration, which can benefit ligand-similarity-based virtual screening. LigMate is freely available for noncommercial users at http://cao.labshare.cn/ligmate/.

2.
J Clin Microbiol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148709

RESUMO

Background: Bacterial vaginosis (BV) is caused by the excessive and imbalanced growth of bacteria in vagina, affecting 30-50% of women in their lives. Gram stain followed by Nugent scoring based on bacterial morphotypes under the microscope (NS) has been considered the golden standard for BV diagnosis, which is often labor-intensive, time-consuming, and variable results from person to person.Methods: We developed and optimized a convolutional neural networks (CNN) model, and evaluated its ability to automatically identify and classify three categories of Nugent scores from microscope images. The CNN model was first established with a panel of microscopic images with Nugent scores determined by experts. The model was trained by minimizing the cross entropy loss function and optimized by using a momentum optimizer. The separate test sets of images collected from three hospitals were evaluated by the CNN models.Results: The CNN model consisted of 25 convolutional layers, 2 pooling layers, and a fully connected layer. The model obtained 82.4% sensitivity and 96.6% specificity on the 5,815 validation images when considered altered vaginal flora and BV as the positive samples, which was better than the top-level technologists and obstetricians in China. The ability of generalization for our model was strong that it obtained 75.1% accuracy of three categories of Nugent scores on the independent test set of 1082 images, which was 6.6% higher than the average of three technologists, who are with a bachelor degree in medicine and eligible making diagnostic decisions. When three technologists ran one specimen in triplicate, the precision of three categories of Nugent scores was 54.0%. 103 samples diagnosed by two technologists at different days showed repeatability of 90.3%.Conclusion: The CNN model over-performed human healthcare practitioners on accuracy and stability for three categories of Nugent scores diagnosis. The deep learning model may offer translational applications in automating diagnosis of bacterial vaginosis with proper supporting hardware.

3.
J Exp Bot ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206180

RESUMO

The BES1/BZR1 transcription factors regulate the expression of brassinosteroid responsive genes and play pivotal roles in plant development. However, the function of BES1/BZR1 regulating kernel development remains unclear. In this study, maize ZmBES1/BZR1-5 is found to positively regulate kernel size. Candidate-gene association analysis showed that four and three SNPs related to ZmBES1/BZR1-5 were significantly associated with kernel width and 100-kernel weight in 513 diverse maize inbred lines, respectively. Overexpression of ZmBES1/BZR1-5 gene in Arabidopsis and rice both significantly increased seed size and weight, as well as smaller kernel produced in maize Mu transposon insertion and EMS mutants. The ZmBES1/BZR1-5 protein contains bHLH and BAM domains, shows no transcriptional activity as monomer but forms homodimer through BAM domain, and locates in nucleus. Chromatin immunoprecipitation sequencing (ChIP-seq), yeast one-hybrid (Y1H) and dual-luciferase assay demonstrate that ZmBES1/BZR1-5 protein binds to the promoter of AP2/EREBP genes (Zm00001d010676 and Zm00001d032077) and inhibits their transcription. cDNA library screening shows that ZmBES1/BZR1-5 interacts with casein kinase II subunit ß4 (ZmCKIIß4) and ferredoxin 2 (ZmFdx2) in vitro and vivo, respectively. Taken together, the study suggests that ZmBES1/BZR1-5 positively regulates kernel size and provides new insights into understanding the mechanism of kernel development in maize.

4.
J Hazard Mater ; : 124490, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33199140

RESUMO

A number of epigenetic modulating chemicals are known to affect multiple generations of a population from a single ancestral exposure, thus posing transgenerational hazards. The present study aimed to establish a high-throughput (HT) analytical workflow for cost-efficient concentration-response analysis of epigenetic and phenotypic effects, and to support the development of novel Adverse Outcome Pathway (AOP) networks for DNA methyltransferase (DNMT) inhibitor-mediated transgenerational effects on aquatic organisms. The model DNMT inhibitor 5-azacytidine (5AC) and the model freshwater crustacean Daphnia magna were used to generate new experimental data and served as prototypes to construct AOPs for aquatic organisms. Targeted HT bioassays (DNMT ELISA, MS-HRM and qPCR) in combination with multigenerational ecotoxicity tests revealed concentration-dependent transgenerational (F0-F3) effects of 5AC on total DNMT activity, DNA promoter methylation, gene body methylation, gene transcription and reproduction. Top sensitive toxicity pathways related to 5AC exposure, such as apoptosis and DNA damage responses were identified in both F0 and F3 using Gaussian Bayesian network modeling. Two novel epigenetic AOP networks on DNMT inhibitor mediated one-generational and transgenerational effects were developed for aquatic organisms and assessed for the weight of evidence. The new HT analytical workflow and AOPs can facilitate future ecological hazard assessment of epigenetic modulating chemicals.

5.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(5): 686-690, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33131525

RESUMO

Hereditary angioedema(HAE)is a rare,hereditary disease characterized by recurrent subcutaneous and submucosal edema.Known genes associated with the pathogenesis of HAE include C1 esterase inhibitor gene,FⅫ gene,plasminogen gene,and angiopoietin 1 gene.Based on the known gene mutations,this review analyzes the effects of these mutations on the functions of protein products to figure out the possible pathogenic mechanism,so as to provide references for further investigations on the pathogenesis of HAE and seeking new prevention and treatment approaches.

6.
Int J Environ Health Res ; : 1-10, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33164565

RESUMO

The aim of this study was to evaluate the impact of the COVID-19 pandemic on the psychological health and mental health-related lifestyles in Shanghai, China. In the cross-sectional study conducted in May 2020, participants were asked to complete a validated questionnaire including the impact of event scale (IES), social and family support, lifestyle changes, and indicators of negative mental health impact. A total of 430 participants (303 females and 127 males) completed the questionnaire. The overall mean of IES score was 32.3 ± 12.2, indicating a moderate-to-severe mental stress impact. Moreover, there were 68.4% of participant who had IES score ≥26. Females were more likely to get increased support from family and friends, share feeling with them and others, and care for family member's feeling (all P < 0.05). In conclusion, although the COVID-19 pandemic was correlated with high stressful impact, it had associated with some positive mental-health related changes in an urban environment.

7.
BMJ Open ; 10(11): e043560, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33148769

RESUMO

OBJECTIVE: To investigate the influence of demographic and socioeconomic factors on the COVID-19 case-fatality rate (CFR) globally. DESIGN: Publicly available register-based ecological study. SETTING: Two hundred and nine countries/territories in the world. PARTICIPANTS: Aggregated data including 10 445 656 confirmed COVID-19 cases. PRIMARY AND SECONDARY OUTCOME MEASURES: COVID-19 CFR and crude cause-specific death rate were calculated using country-level data from the Our World in Data website. RESULTS: The average of country/territory-specific COVID-19 CFR is about 2%-3% worldwide and higher than previously reported at 0.7%-1.3%. A doubling in size of a population is associated with a 0.48% (95% CI 0.25% to 0.70%) increase in COVID-19 CFR, and a doubling in the proportion of female smokers is associated with a 0.55% (95% CI 0.09% to 1.02%) increase in COVID-19 CFR. The open testing policies are associated with a 2.23% (95% CI 0.21% to 4.25%) decrease in CFR. The strictness of anti-COVID-19 measures was not statistically significantly associated with CFR overall, but the higher Stringency Index was associated with higher CFR in higher-income countries with active testing policies (regression coefficient beta=0.14, 95% CI 0.01 to 0.27). Inverse associations were found between cardiovascular disease death rate and diabetes prevalence and CFR. CONCLUSION: The association between population size and COVID-19 CFR may imply the healthcare strain and lower treatment efficiency in countries with large populations. The observed association between smoking in women and COVID-19 CFR might be due to the finding that the proportion of female smokers reflected broadly the income level of a country. When testing is warranted and healthcare resources are sufficient, strict quarantine and/or lockdown measures might result in excess deaths in underprivileged populations. Spatial dependence and temporal trends in the data should be taken into account in global joint strategy and/or policy making against the COVID-19 pandemic.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33210262

RESUMO

BACKGROUND AND OBJECTIVE: All oral direct-acting antivirals (DAAs) have shown excellent efficacy and safety in Chinese patients with chronic hepatitis C (CHC). However, the cost of DAAs used to be expensive; therefore, large numbers of patients had no access to DAAs in China. Recently, prices have been greatly reduced. The objective of this study was to evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/velpatasvir (SOF/VEL), elbasvir/grazoprevir (EBR/GZR) and glecaprevir/pibrentasvir (GLE/PIB) in Chinese CHC patients stratified by hepatitis C virus (HCV) genotype (GT), cirrhosis status, and treatment history. METHODS: On the basis of a Chinese healthcare perspective, a Markov model was constructed to estimate the lifetime costs and health outcomes of patients treated with different DAA regimens. Chinese-specific clinical, cost, and utility inputs were obtained or calculated from published sources and expert opinions. Costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were reported as primary outcomes. Base-case analysis and sensitivity analysis were conducted. RESULTS: At a willing-to-pay (WTP) threshold of US$30,081/QALY (calculated by three times the GDP per capita in China), SOF/VEL was cost-effective in patients with HCV GT 1, 3, and 6 infections, and the probabilities that SOF/VEL was cost-effective were 9.7-75.7%, 39.1-63.9%, and 35.6-88.0%, respectively. For GT2 patients, noncirrhotic patients, treatment-naïve patients, and treatment-experienced patients, LDV/SOF was the most cost-effective regimen, and the probabilities of cost-effectiveness for each of these groups was 92.1-99.8%, 89.9-99.0%, 61.6-91.2%, and 99.3-100.0%, respectively below the WTP threshold. The GLE/PIB regimen (12-week duration) was the most cost-effective in cirrhotic patients, whereas the probability of its cost-effectiveness varied with that of EBR/GZR (4.1-93.8% versus 6.2-93.3%) below the WTP threshold. CONCLUSIONS: Overall, SOF/VEL and LDV/SOF regimens are more likely to be cost-effective among various subgroups of Chinese patients with CHC.

9.
Front Immunol ; 11: 1933, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072067

RESUMO

Background: Limited treatment strategies are available for squamous-cell lung cancer (SQLC) patients. Few studies have addressed whether immune-related genes (IRGs) or the tumor immune microenvironment can predict the prognosis for SQLC patients. Our study aimed to construct a signature predict prognosis for SQLC patients based on IRGs. Methods: We constructed and validated a signature from SQLC patients in The Cancer Genome Atlas (TCGA) using bioinformatics analysis. The underlying mechanisms of the signature were also explored with immune cells and mutation profiles. Results: A total of 464 eligible SQLC patients from TCGA dataset were enrolled and were randomly divided into the training cohort (n = 232) and the testing cohort (n = 232). Eight differentially expressed IRGs were identified and applied to construct the immune signature in the training cohort. The signature showed a significant difference in overall survival (OS) between low-risk and high-risk cohorts (P < 0.001), with an area under the curve of 0.76. The predictive capability was verified with the testing and total cohorts. Multivariate analysis revealed that the 8-IRG signature served as an independent prognostic factor for OS in SQLC patients. Naive B cells, resting memory CD4 T cells, follicular helper T cells, and M2 macrophages were found to significantly associate with OS. There was no statistical difference in terms of tumor mutational burden between the high-risk and low-risk cohorts. Conclusion: Our study constructed and validated an 8-IRG signature prognostic model that predicts clinical outcomes for SQLC patients. However, this signature model needs further validation with a larger number of patients.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33075026

RESUMO

BACKGROUND: Clinical equipoise exists regarding optimal sequencing in the definitive management of choledocholithiasis. Our current study compares sequential biliary ductal clearance and cholecystectomy at an interval to simultaneous laparoendoscopic management on index admission in a pragmatic retrospective manner. METHODS: Records were reviewed for all patients admitted between January 2015-December 2018 to a Swedish and an Irish university hospital. Both hospitals differ in their practice patterns for definitive management of choledocholithiasis. At the Swedish hospital, patients with choledocholithiasis underwent laparoscopic cholecystectomy with intra-operative rendezvous ERCP at index admission (one-stage). In contrast, interval day-case laparoscopic cholecystectomy followed index admission ERCP (two-stage) at the Irish hospital. Clinical characteristics, post-procedural complications, and inpatient duration were compared between cohorts. RESULTS: Three hundred and fifty-seven patients underwent treatment for choledocholithiasis during the study period, of whom 222(62.2%) underwent a one-stage procedure in Sweden, while 135(37.8%) underwent treatment in two stages in Ireland. Patients in both cohorts were closely matched in terms of age, sex, and pre-operative serum total bilirubin. Patients in the one-stage group exhibited a greater inflammatory reaction on index admission (peak C-reactive protein = 136±137 vs. 95±102mg/L,p=0.024), had higher incidence of co-morbidities (age-adjusted Charlson Comorbidity Index ≥3:37.8% vs 20.0%,p=0.003), and overall were less fit for surgery (ASA ≥3: 11.7% vs. 3.7%,p < 0.001). Despite this, a significantly-shorter mean time to definitive treatment, i.e., cholecystectomy (3.1±2.5 vs. 40.3±127 days,p=0.017), without excess morbidity, was seen in the one-stage compared to the two-stage cohort. Patients in the one-stage cohort experienced shorter mean post-procedure length of stay(3.0±4.7 vs 5.0±4.6 days,p < 0.001) and total length of hospital stay(6.5±4.6 vs 9.0±7.3 days,p=0.002). The only significant difference in postoperative complications between the cohorts was urinary retention, with a higher incidence in the one-stage cohort (19% vs. 1%, p=0.004). CONCLUSION: Where appropriate expertise and logistics exist within developing models of Acute Care Surgery worldwide, consideration should be given to index-admission laparoscopic cholecystectomy with intraoperative ERCP for the treatment of choledocholithiasis. Our data suggest this strategy significantly shortens the time to definitive treatment, decreases total hospital stay without any excess in adverse outcomes.Original Research; Retrospective Cohort Study (Level III).

11.
Am J Case Rep ; 21: e925151, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021971

RESUMO

BACKGROUND Although the V617F mutation in the Janus kinase 2 (JAK2) gene and the breakpoint cluster region-abl1 (BCR-ABL1) oncogene fusion have been considered mutually exclusive in most myeloproliferative neoplasms (MPNs), many recent studies have described patients with both. This report describes a patient with chronic myelogenous leukemia (CML) and the unusual JAK2 R795S mutation and reviews 23 additional patients with JAK2 gene mutations coexisting with myelofibrosis (MF) and CML. CASE REPORT A 50-year-old woman with MF experienced rapid disease progression 3 weeks later, accompanied by severe abdominal pain and a white blood cell count of 257.45×109/l. Karyotype analysis indicated that she was 46, XY, Philadelphia (Ph) (+) and BCR-ABL1 positive. Bone marrow aspiration after 1 cycle of chemotherapy and treatment with dasatinib showed that her marrow was hypercellular, with an increased number of megakaryocytes and 48.5% myeloblasts expressing the myeloid antigens CD33, CD13, CD34, CD117, and CD71. Next-generation sequencing identified a rare JAK2 R795S mutation. She was diagnosed with CML in blast phase, and was successfully treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). CONCLUSIONS JAK2 gene mutations, including the rare JAK2 R795S mutation, can coexist with BCR-ABL1 in patients with MPNs. The clinical course of MPN in patients with both BCR-ABL1 and JAK2 mutations may be different from that in patients with classical MPNs.

12.
BMC Bioinformatics ; 21(Suppl 14): 408, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998723

RESUMO

BACKGROUND: Second messengers, c-di-GMP and (p)ppGpp, are vital regulatory molecules in bacteria, influencing cellular processes such as biofilm formation, transcription, virulence, quorum sensing, and proliferation. While c-di-GMP and (p)ppGpp are both synthesized from GTP molecules, they play antagonistic roles in regulating the cell cycle. In C. crescentus, c-di-GMP works as a major regulator of pole morphogenesis and cell development. It inhibits cell motility and promotes S-phase entry by inhibiting the activity of the master regulator, CtrA. Intracellular (p)ppGpp accumulates under starvation, which helps bacteria to survive under stressful conditions through regulating nucleotide levels and halting proliferation. (p)ppGpp responds to nitrogen levels through RelA-SpoT homolog enzymes, detecting glutamine concentration using a nitrogen phosphotransferase system (PTS Ntr). This work relates the guanine nucleotide-based second messenger regulatory network with the bacterial PTS Ntr system and investigates how bacteria respond to nutrient availability. RESULTS: We propose a mathematical model for the dynamics of c-di-GMP and (p)ppGpp in C. crescentus and analyze how the guanine nucleotide-based second messenger system responds to certain environmental changes communicated through the PTS Ntr system. Our mathematical model consists of seven ODEs describing the dynamics of nucleotides and PTS Ntr enzymes. Our simulations are consistent with experimental observations and suggest, among other predictions, that SpoT can effectively decrease c-di-GMP levels in response to nitrogen starvation just as well as it increases (p)ppGpp levels. Thus, the activity of SpoT (or its homologues in other bacterial species) can likely influence the cell cycle by influencing both c-di-GMP and (p)ppGpp. CONCLUSIONS: In this work, we integrate current knowledge and experimental observations from the literature to formulate a novel mathematical model. We analyze the model and demonstrate how the PTS Ntr system influences (p)ppGpp, c-di-GMP, GMP and GTP concentrations. While this model does not consider all aspects of PTS Ntr signaling, such as cross-talk with the carbon PTS system, here we present our first effort to develop a model of nutrient signaling in C. crescentus.


Assuntos
Caulobacter crescentus/fisiologia , Modelos Teóricos , Sistemas do Segundo Mensageiro , Pontos de Checagem do Ciclo Celular , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Nitrogênio/metabolismo , Fosfotransferases/metabolismo , Sistemas do Segundo Mensageiro/fisiologia
13.
Biomater Sci ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33108411

RESUMO

Insufficient drug release and poor drug penetration compromise the efficacy of chemotherapy and hinder clinical translations in nanoparticle-based drug delivery systems. Inspired by the excretion process of exosomes, herein, silk fibroin-based doxorubicin preloaded calcium carbonates (CCs-SF/DOX) that integrate tumor-derived extracellular vesicle (EV) generation attributes are constructed for triple therapies of "local chemotherapy-therapeutic EVs-synergistic immunotherapy" (CT-EVs-IT). Assisted by low-intensity focused ultrasound, increased intracellular influx of CCs-SF/DOX can be achieved through acoustic pertubation-facilitated delivery or endocytic uptake. The acidic endosome or lysosome accelerates the release of DOX in the cancer cells for efficient cytotoxicity. Residual CCs-SF/DOX or uploaded DOX from dead/dying cells are encapsulated in vesicles and fuse with the plasma membrane of cells, triggering excretion of vesicles to extracellular space and responding to the acidic environment in the ECM, repeating the process infecting neighboring cancer cells, and exerting deep drug penetration based EV therapy. Meanwhile, CCs-SF/DOX scavenging of H+ promotes M1-like macrophage polarization, reversing immunosuppressive TME, and locally released chemotherapeutics potentiate antitumor immune response; both facilitate PD1/PD-L1 checkpoint blockade combined immunotherapy. Taken together, therapies of CT-EVs-IT assisted by LIFU contribute to achieve amplified antitumor benefits.

14.
Atherosclerosis ; 313: 150-155, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33059161

RESUMO

BACKGROUND AND AIMS: We aimed to identify plasma protein biomarkers related to inflammation that correlated with physiological measurements of vascular function and structure in healthy individuals. METHODS: We used the OLINK proteomics panel, which measures 92 inflammatory proteins, in 834 young, healthy non-smokers (ages 18-26). Principal component analysis (PCA) was employed to identify patterns of proteins. The following measurements were used: pulse-wave velocity (PWV), carotid intima-media thickness (cIMT) and augmentation index (AIX). Established cardiovascular risk factors were included in multivariable models. RESULTS: PCA showed four principal components (PC 1, PC 2, PC 3, PC 4). PC 3, comprising proteins related to hemostasis, was significantly and inversely correlated with PWV. Among the proteins with the highest factor loadings on PC 3, uPA was negatively correlated with PWV in multivariable regression models. AIX was significantly correlated with PC 2, comprising inflammatory cytokines. Among the proteins with the highest factor loadings on PC 2, interleukin-6 was significantly correlated with AIX in the multivariable model. cIMT was significantly correlated with PC 4, comprising proteins related to chemotaxis. Among the proteins with the highest factor loadings on PC 4, fractalkine was significantly correlated with cIMT in the multivariable model. CONCLUSIONS: In young, healthy individuals, OLINK inflammatory proteins correlated with measures of vascular status. Each of the three measures PWV, AIX, and cIMT, which target different parts of the vasculature, correlated with its own specific protein signature, indicating that different subsets of inflammatory mediators affect different parts of the vasculature and are detectable already in young healthy adults.

15.
PLoS One ; 15(10): e0241202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33108375

RESUMO

BACKGROUND: Banxia Xiexin decoction (BXD), a classical formula of traditional Chinese medicine (TCM), has been wildly used for chronic atrophic gastritis (CAG) patients with the cold-heat complex syndrome in China, and achieved satisfied effects. However, the clinical effects of it remains unclear. PURPOSE: The purpose of this article is to evaluate the clinical efficacy and safety of BXD for CAG treatment. METHODS: We searched seven electronic databases including Ovid, Embase, PubMed, Cochrane Library, Wan-fang database, VIP (Chinese Scientific Journals Database) and CNKI (China National Knowledge Infrastructure) from their inception to September 21, 2020. We used Jadad scale and Cochrane Collaboration's risk of bias tool to make evaluation of methodological quality. Revman 5.3 statistical software was used for statistical processing to evaluate the clinical efficacy and safety of BXD. RESULTS: 26 randomized controlled trials (RCTs) totaling 1985 patients were identified for analysis. Meta-analysis showed that BXD treatment was more effective (RR 1.29; 95%CI 1.24, 1.35; P<0.00001) and safe (MD 0.33; 95%CI 0.18, 0.58; P = 0.0002) than Chinese patent medicine + western medicine. Furthermore, BXD had improvement on symptoms scores such as stomach distending pain, and belching. Besides, BXD was more effective in inhibiting Helicobacter Pylori (HP), improving HP-related inflammation, and relieving the degree of glandular atrophy, intestinal metaplasia (IM), and dysplasia of gastric mucosa (GM). CONCLUSIONS: The meta-analysis showed that BXD was more effective and safer for CAG patients than the control group. However, due to limitations of methodological quality and small sample size of the included studies, further standardized research of rigorous design should be needed.

16.
J Mol Diagn ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33122141

RESUMO

The prevalence and clinical relevance of viremia in patients with coronavirus disease 2019 (COVID-19) are not well-studied. A prospective cohort study was designed to investigate blood viral load and clearance kinetics in 52 patients (median age, 62 years; 31 [59.6%] male) and explore their association with clinical features and outcomes based on a novel one-step reverse-transcription droplet digital PCR (RT-ddPCR). By using one-step RT-ddPCR, 92.3% (48/52) of this cohort was quantitatively detected with viremia. The concordance between the blood and oropharyngeal swab tests was 60.92% (53/87). One-step RT-ddPCR was tested with a 3.03% of false positive rate and lower 50% confidence interval of detection (LOD50) at 54.026 copies/ml plasma. In all critical patients, the blood viral load was not eliminated, while the general and severe patients showed similar ability to clear the viral load. The viral loads in critical patients were significantly higher than those in general and severe counterparts. Among the 52 patients, 30 (58%) were discharged from hospital. Among half of 30 discharged patients, blood viral load remained positive, of which 76.9% (10/13) completely cleared their blood viral load at follow-up. Meanwhile, none of their close contacts had the evidence of infection. Quantitative determination of blood viral test is of great clinical significance to the management of COVID-19 patients.

17.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(10): 1390-1398, 2020 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-33118509

RESUMO

OBJECTIVE: To investigate the effect of miR-133b on cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion (I/R) and explore the mechanism. METHODS: Thirty-six adult SD rats were randomized into sham-operated group, I/R group, AdmiR-NC group and AdmiR-133b group, and rat models of myocardial I/R were established in the latter 3 groups with myocardial injections of saline or recombinant adenoviruses in the left ventricle. The expression of MiR-133b was detected using RT-qPCR, and cardiac function of the rats was determined using FDP 1 HRV and BRS analysis system. Serum CK-MB and cTnI levels were determined by ELISA, myocardial injury was evaluated with HE staining, cardiomocyte apoptosis was detected by flow cytometry, and ROS content was determined using a DCFH-DA probe. In the in vitro experiment, H9C2 myocardial cells with hypoxia/reoxygenation (H/R) treatment were transfected with Mir-NC or MiR-133b mimic, and the cellular expression of MiR-133b, cell apoptosis, and ROS content were determined. Dual luciferase reporter assay was performed to verify the targeting relationship between miR-133b and YES1. The effects of pc-YES1 or miR-133b mimic transfection on YES1 expression, apoptosis, and ROS content in H9C2 cells were evaluated. RESULTS: Compared with those in I/R group, miR-133b expression was obviously up-regulated, LVEDP, cTnI and CK-MB levels were significantly decreased, and LVSP, +dp/dt, -dp/dt, HR and CF levels were increased in admiR-133b group (P < 0.01). The rats in admiR-133b group showed obviously reduced pathological damage, cell apoptosis and ROS content compared with those in I/ R group (P < 0.01). In H9C2 cells exposed to H/R, transfection with miR-133b mimic significantly up-regulated miR-133b expression and decreased cell apoptosis and ROS content (P < 0.01). The results of dual luciferase reporter assay suggested a direct targeting relationship between miR-133b and YES1, and MiR-133b mimic transfection significantly down-regulated YES1 protein expression in cells with H/R exposure (P < 0.01). Co-transfection with pc-YES1 reversed the effect of miR-133b overexpression on myocardial cell apoptosis and ROS accumulation. CONCLUSIONS: miR-133b can inhibit I/R-induced myocardial cell apoptosis and ROS accumulation by targeting YES1 to reduce myocardial I/R injury in rats.


Assuntos
Traumatismo por Reperfusão Miocárdica , Animais , Apoptose , MicroRNAs/genética , Miócitos Cardíacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio
18.
ACS Appl Mater Interfaces ; 12(43): 48420-48431, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33073973

RESUMO

Photothermal therapy (PTT) as a noninvasive and effective thermal therapeutic approach has attracted tremendously increasing interest because it can effectively eliminate the primary tumor and generate tumor-associated antigens, which could elicit antitumor immune responses. Herein, we report on the rational design and fabrication of copper sulfide (CuS)-based nanoplatform for cancer photothermal immunotherapy. The as-prepared core-shell CuS@mSiO2-PFP-PEG (CPPs) nanocomposites possess high biocompatibility, photoacoustic (PA)/ultrasound (US) imaging, and strong PTT effect upon 808 nm laser irradiation, indicating that the nanocomposites have a promising application in diagnosis and treatment of breast cancer with molecular classification. Importantly, we also elucidated that the CPP-triggered PTT in combination with anti-PD-1 checkpoint blockade therapy can not only obliterate primary tumor but also inhibit metastatic tumor in tumor-bearing mice. We believe that the CPPs have a good probability to serve as a useful nanoplatform for PTT, and this approach may provide a promising strategy for tumor-therapeutic modality with immunotherapy.

19.
Cancer Epidemiol Biomarkers Prev ; 29(11): 2230-2234, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33087343

RESUMO

BACKGROUND: Highly increased risk of injuries has been noted around the time of cancer diagnosis. Whether there is a similar increase in risk around the diagnosis of cervical cancer and its precursor lesions was unknown. METHODS: We performed a cohort study including 3,016,307 Swedish women that participated in cervical screening during 2001 to 2012. We calculated the incidence rates (IR) of hospitalized iatrogenic or noniatrogenic injuries during the diagnostic workup, and the time interval from smear or punch biopsy until surgical treatment or 2 months after the last smear or biopsy, among women with invasive cervical cancer (ICC) or its precursor lesions. We calculated the IRs of injuries during the 2 months after a normal smear among the other women as reference. IR ratios (IRR) and 95% confidence intervals (CI) were calculated using Poisson regression. RESULTS: Compared with other women, there was an increased rate of iatrogenic injuries during the diagnostic workup of women with ICC (IR, 0.58 per 1,000 person-months; IRR, 8.55; 95% CI, 3.69-19.80) as well as of women with cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ (IR, 0.09 per 1,000 person-months; IRR, 3.04; 95% CI, 1.73-5.34). We also found an increased rate of noniatrogenic injuries during the diagnostic workup of women with invasive cancer (IR, 0.65 per 1,000 person-months; IRR, 2.48; 95% CI, 1.30-4.47). CONCLUSIONS: Although rare, there was an increased risk of inpatient care for iatrogenic and noniatrogenic injuries during the diagnostic workup of women with ICC. IMPACT: Women experienced burden of medical complications and psychologic distress around diagnosis of a potential cervical cancer.

20.
Orphanet J Rare Dis ; 15(1): 257, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962702

RESUMO

BACKGROUND: Hereditary angioedema (HAE) is a rare disease with potential life-threatening risks. To study the natural course of HAE under therapy-free conditions throughout patient life is essential for practitioners and patients to avoid possible risk factors and guide treatment. OBJECTIVES: Describe the natural course of HAE and explore possible risk factors, providing new clues for guiding clinical prevention and treatment. METHODS: A web-based survey was conducted in 103 Chinese patients with type 1 HAE. Disease progression at different age stages was provided by each participant. The data for exploring the natural course of HAE composed of two parts: one came from the participants who had never adopted any prophylactic drug for HAE; the other was from the patients with a history of medication, but only the periods before they got confirmed diagnosis and received medications were analyzed. The demographic characteristics, lifestyles, disease severity, and family history were also collected. RESULTS: Among 103 patients, 14 (13.6%) had their first HAE attack before 10 years old and 51 (49.5%) between 10 and 19. The disease worsened in 83.3% of the patients in their twenties. The proportion of patients with symptoms alleviated increased after the age of 30 years old, but the disease maintained relatively severe in most cases before 50. The participants also reported 233 members shared similar symptoms of angioedema in their family and 30 had died of laryngeal edema with the median death age of 46 years old. The disease severity was not observed to be affected significantly by gender, BMI, alcohol or smoking. CONCLUSIONS: We summarized HAE progression patterns under therapy-free conditions, showing the natural course of HAE development along with aging. Long-term prophylaxis and symptomatic treatment are recommended for all HAE patients, especially young and middle-aged and might be adjusted depending on the disease progression.

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