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1.
Birth Defects Res ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030311

RESUMO

Mutations in the transforming growth factor ß-binding protein-like domain 5 (TB5) region of FBN1 can lead to autosomal acromelic dysplasia and Marfan syndrome, which are two diseases with apparently opposite phenotypes. We identified six patients with acromelic dysplasia carrying either the previously reported mutations c.5284G > A (p.Gly1762Ser) and c.5096A > G (p.Tyr1699Cys) or the novel mutation c.5260G > A (p.Gly1754Ser). A systematic review of patients with mutations in the FBN1-TB5 region showed that acromelic dysplasia is caused only by in-frame amino acid substitutions. In contrast, truncating mutations in the FBN1-TB5 have been reported only in Marfan syndrome. Acromelic dysplasia subtypes that share symptoms with Marfan syndrome are associated with FBN1-TB5 disulfide disruptions, which are also commonly found in Marfan syndrome. These results suggest that the type and location of mutations in the FBN1-TB5 region determine the clinical spectrum of fibrillinopathy.

2.
BMC Geriatr ; 20(1): 387, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023491

RESUMO

BACKGROUND: Postoperative cognitive dysfunction is a common postoperative complication in elderly patients. In elderly patients, the decline of organ function and neuromuscular junction function make them more sensitive to muscle relaxants. They are more likely to experience residual muscle relaxation after surgery, which may cause various adverse events. Neostigmine, a commonly used muscle relaxant antagonist, can reduce the expression of inflammatory factors, thereby reducing the pro-inflammatory response and neurodegeneration of the cerebral cortex and hippocampus after surgery. The study aimed at observing the effect of different doses of neostigmine on postoperative cognitive function and peripheral inflammatory factors in elderly patients. METHODS: One hundred thirty-two elderly patients who underwent a radical section of gastrointestinal cancer at First Affiliated Hospital of Dalian Medical University were divided into neostigmine and saline groups at a 2:1 ratio. Neostigmine was intravenously injected in the post-anesthesia care unit (PACU) according to the train-of-four ratio (TOFR) T4/T1. When TOFR was ≤0.5, 0.04 mg/kg neostigmine was administered, whereas when TOFR was > 0.5, 0.02 mg/kg neostigmine was injected. The main observation indexes were cognitive function, interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) in peripheral blood at the different times before and after the surgery. Secondary observation indicators include the number of atropine injection, extubating time, PACU residence time, incidence of hypoxemia, hypercapnia, and postoperative nausea and vomiting in PACU, time of exhaustion, and length of hospitalization. RESULTS: The extubating and PACU times in 0.04 mg/kg and 0.02 mg/kg groups were significantly shorter than those in the control group (P < 0.001). The incidence of early postoperative cognitive decline in 0.04 mg/kg and 0.02 mg/kg groups was 10 and 15.7%, respectively, which were significantly lower than those in the control group (P = 0.013). CONCLUSION: In elderly patients, 0.02-0.04 mg/kg neostigmine could significantly reduce the incidence of early postoperative cognitive decline without affecting peripheral inflammatory factors. TRIAL REGISTRATION: Trial registration: Chinese Clinical Trial Registry, ChiCTR2000031739. Registered 8 April 2020 - Retrospectively registered, http://www.medresman.org.cn .

3.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(10): 1233-1237, 2020 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-33063485

RESUMO

Objective: To investigate the technique of optimizing the location of femoral attachment in medial patellofemoral ligament (MPFL) reconstruction assisted with arthroscopy and evaluate the effectiveness. Methods: Between January 2014 and September 2018, 35 patients with patellar dislocation were admitted. There were 14 males and 21 females with an average age of 22.6 years (range, 16-38 years). All patients had a history of knee sprain. The disease duration ranged from 1 to 7 days (mean, 2.8 days). Patellar dislocation occurred 2-4 times (mean, 2.5 times). The preoperative Lysholm score and Kujala score were 47.60±11.24 and 48.37±9.79, respectively. The patellar congruence angle was (31.40±6.81)°, the patellar tilt angle was (29.95±5.44)°, the lateral patellofemoral angle was (-11.46±5.18)°, and the tibial tubercle-trochlear groove distance was (16.66±1.28) mm. All patients were treated by MPFL reconstruction with the semitendinosus tendon under arthroscopy. During operation, the suture anchors were inserted into the midpoint and the 1/3 point of superomedial edge of the patella. Then, the femoral tunnels were created in medial femoral condyle through limited excision. For tendon fixation, the Kirschner wires were inserted into adductor tubercle, medial epicondyle of femur, and the midpoint between the two points, as well as the anteriorly and posteriorly. Afterwards, the changes of ligament length and tension, patellar tracking, and the relationship of patella and femoral trochlea were evaluated, thereby determining the optimized femoral attachment for MPFL reconstruction. Finally, the patellar congruence angle, patellar tilt angle, and lateral patellofemoral angle were measured by imaging to assess the relationship of patella and femoral trochlea. Moreover, Lysholm score and Kujala score were used to evaluate the knee joint function. Results: All incisions healed by first intention without infection. All patients were followed up 12-18 months (mean, 15.4 months). At 12 months, the Lysholm score was 94.40±3.99 and the Kujala score was 92.28±4.13, which were significant higher than those before operation ( P<0.05). No patellar dislocation occurred during follow-up. At 12 months, the patellar congruence angle was (6.57±4.59)°, the patellar tilt angle was (9.73±2.82)°, the lateral patellofemoral angle was (7.14±4.63)°, which were superior to those before operation ( P<0.05). Conclusion: During the MPFL reconstruction under arthroscopy, a higher positioning accuracy for the femoral attachment and satisfactory effectiveness can be obtained by evaluating MPFL length and tension, patellofemoral joint kinematics, and patellar tracking.


Assuntos
Luxação Patelar , Adolescente , Adulto , Artroscopia , Feminino , Humanos , Articulação do Joelho/cirurgia , Ligamentos Articulares/cirurgia , Masculino , Patela , Luxação Patelar/cirurgia , Adulto Jovem
4.
Comput Biol Chem ; 89: 107383, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33032037

RESUMO

RUNX family transcription factor 2 (RUNX2) overexpression has been found in various human malignancies. However, the expression levels of RUNX2 mRNA and protein in lung adenocarcinoma (LUAD) were not investigated. This study aims to thoroughly analysis the expression level and potential mechanisms of RUNX2 mRNA in LUAD. We applied in-house immunohistochemistry, high-throughput RNA-sequencing, and gene microarrays to comprehensively investigate the expression level of RUNX2 in LUAD. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to assess the integrated expression value of RUNX2 in LUAD. The hazard ratios (HRs) were integrated to evaluate the overall prognostic effect of RUNX2 on the LUAD patients. The differentially expressed genes (DEGs) of LUAD, the potential target genes of RUNX2, and its co-expressed genes were overlapped to obtain a set of specific genes for GO and KEGG enrichment analyses. RUNX2 overexpression in LUAD was validated using a large number of cases (2 418 LUAD and 1 574 non-tumor lung samples). The pooled SMD was 0.85 (95 % CI: 0.64-1.05) and the area under the curve (AUC) of the SROC was 0.86 (95 %CI: 0.83-0.89). The integrated HR was 1.20 [1.04-1.38], indicating that increased expression of RUNX2 was an independent risk factor for the poor survival of the LUAD patients. RUNX2 and its transcriptionally regulates potential target genes may promote cell proliferation and drug resistance of LUAD by modulating the cell cycle and MAPK signaling pathways. RUNX2 can provide new research directions for targeted drug therapy and drug resistance for LUAD treatment.

5.
Environ Pollut ; 268(Pt B): 115676, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33038572

RESUMO

Little is known about interactive effects of pH-aluminum (Al) on reactive oxygen species (ROS) and methylglyoxal (MG) metabolisms in plants. Citrus sinensis seedlings were fertilized with nutrient solution at an Al concentration of 1 or 0 mM and a pH of 4.0, 3.5, 3.0 or 2.5 for 18 weeks. Thereafter, gas exchange and chlorophylls in leaves, H2O2 generation, electrolyte leakage, total soluble proteins, MG, malondialdehyde (MDA), antioxidants, sulfur-containing compounds, enzymes [viz., antioxidant enzymes, sulfur metabolism-related enzymes, ascorbate oxidase, phosphomannose isomerase, glyoxalase I and glyoxalase II] involved in ROS and MG detoxification in leaves and roots were measured. Effects of low pH and Al-toxicity on these parameters displayed obvious synergism. Without Al-toxicity, low pH increased H2O2 production, electrolyte leakage, MDA and MG concentrations by 45.7%-90.3% (52.4%-73.6%), 24.3%-74.5% (26.7%-86.2%), 18.6%-44.8% (35.6%-53.7%) and 16.3%-47.1% (13.8%-51.7%) in leaves (roots) relative to pH 4, respectively; low pH-induced upregulation of enzymes involved in ROS and MG detoxification and sulfur-containing compounds in leaves and/or roots could not protect them against oxidative damage. At pH 2.5-3.0, Al-toxicity increased H2O2 production, electrolyte leakage, MDA and MG concentrations by 34.2%-35.5% (23.9%-72.7%), 10.2%-29.5% (23.7%-56.8%), 15.6%-35.7% (27.5%-33.9%) and 21.5%-26.8% (21.0%-49.2%) in leaves (roots), respectively, and decreased total soluble protein concentration by 46.2%-47.4% (18.8%-20.8%) in leaves (roots); at pH 3.5-4.0, Al-toxicity did not affect significantly the five parameters in leaves and roots except for Al-induced increases in root MDA concentration at pH 3.5-4.0 and root electrolyte leakage at pH 3.5, and Al-induced decrease in root total soluble protein concentration at pH 4.0. Raised pH conferred the ability to maintain a balance between production and detoxification of ROS and MG in leaves and roots, thus protecting them against oxidative damage, and hence alleviating Al-induced increase in electrolyte leakage and decrease in total soluble protein level.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1496-1503, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067944

RESUMO

OBJECTIVE: To explore the correlation of SOCS1 gene methylation with the activity of JAK2/STAT signaling pathway, genesis and progress of acute myeloid leukemia. METHODS: Several techniques, such as cell culture, qPCR, MS-PCR, Western bolt, CCK-8 assay, flow cytometry and gene transfection were used to analyze the relation of expression and methylation statues of SOCS1 gene with the genesis and progression of AML in 120 AML patients and leukemia cell lines U937 and THP-1, at the same time to analyze the changes of downstream protein expression in JAK2/STAT signaling pathway and their effect on the growth and apoptosis of leukemia cell lines. RESULTS: The positive rate of WT1/ABL in SOCS1 methylated group was significantly higher than that in SOCS1 non-methylated group, and the complete remission rate of one course treatment in SOCS1-methylated group was significantly lower than that in SOCS1 non-methylated group. The expression level of SOCS1 gene in low methylation rate group was higher, and the expression of down-stream proteins p-JAK2, p-STAT3 and p-STAT5 in JAK2/STAT signaling pathway decreased, while the expression of t-JAK2,t-STAT3 and t-STAT5 was not changed statistically significantly. The growth rate of leukemia cells graduated decreased, and the apoptosis rate of leukemia cells graduated increased along with the enhancement of methylation drug concentration. CONCLUSION: The methylation of SOCS1 gene results in the gene silencing, thereby declines its inhibition on the down-stream proteins in JAK2/STAT signaling pathway, and finally promotes the growth and proliferation of AML cells.


Assuntos
Leucemia Mieloide Aguda , Apoptose , Humanos , Janus Quinase 2 , Leucemia Mieloide Aguda/genética , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3823-3826, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018834

RESUMO

the purpose of targeted muscle reinnervation (TMR) surgery is to provide more electromyography information for prosthetic control by reconstructing the deconstructed structure between the distal nerve and the stump muscle. Functional electrical stimulation (FES) of denervated muscles or proximal nerve stump after peripheral nerve surgery can effectively promote nerve regeneration and muscle function recovery. This pilot divided SD adult male rats into normal control group, denervation group, TMR group, and FES group according to whether they received TMR surgery and whether they received FES after surgery. The results showed that low-frequency electrical stimulation treatment could effectively promote transplanted nerve regeneration and significantly enhances motor function of target muscles.Clinical Relevance-This experiment successfully established TMR rat models, and explored the recovery of injured neuromuscular function by using electrodes implanted intramuscularly and analyzing myoelectric signals, and the use of low-frequency electrical stimulation treatment had a positive effect on the regeneration of the transplanted nerve.


Assuntos
Fenômenos Fisiológicos Musculoesqueléticos , Procedimentos Cirúrgicos Reconstrutivos , Animais , Estimulação Elétrica , Masculino , Regeneração Nervosa , Procedimentos Neurocirúrgicos , Ratos
8.
Lancet Psychiatry ; 7(11): 955-970, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33069318

RESUMO

BACKGROUND: Many potential environmental risk factors, environmental protective factors, and peripheral biomarkers for ADHD have been investigated, but the consistency and magnitude of their effects are unclear. We aimed to systematically appraise the published evidence of association between potential risk factors, protective factors, or peripheral biomarkers, and ADHD. METHODS: In this umbrella review of meta-analyses, we searched PubMed including MEDLINE, Embase, and the Cochrane Database of Systematic Reviews, from database inception to Oct 31, 2019, and screened the references of relevant articles. We included systematic reviews that provided meta-analyses of observational studies that examined associations of potential environmental risk factors, environmental protective factors, or peripheral biomarkers with diagnosis of ADHD. We included meta-analyses that used categorical ADHD diagnosis criteria according to DSM, hyperkinetic disorder according to ICD, or criteria that were less rigorous than DSM or ICD, such as self-report. We excluded articles that did not examine environmental risk factors, environmental protective factors, or peripheral biomarkers of ADHD; articles that did not include a meta-analysis; and articles that did not present enough data for re-analysis. We excluded non-human studies, primary studies, genetic studies, and conference abstracts. We calculated summary effect estimates (odds ratio [OR], relative risk [RR], weighted mean difference [WMD], Cohen's d, and Hedges' g), 95% CI, heterogeneity I2 statistic, 95% prediction interval, small study effects, and excess significance biases. We did analyses under credibility ceilings, and assessed the quality of the meta-analyses with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). This study is registered with PROSPERO, number CRD42019145032. FINDINGS: We identified 1839 articles, of which 35 were eligible for inclusion. These 35 articles yielded 63 meta-analyses encompassing 40 environmental risk factors and environmental protective factors (median cases 16 850, median population 91 954) and 23 peripheral biomarkers (median cases 175, median controls 187). Evidence of association was convincing (class I) for maternal pre-pregnancy obesity (OR 1·63, 95% CI 1·49 to 1·77), childhood eczema (1·31, 1·20 to 1·44), hypertensive disorders during pregnancy (1·29, 1·22 to 1·36), pre-eclampsia (1·28, 1·21 to 1·35), and maternal acetaminophen exposure during pregnancy (RR 1·25, 95% CI 1·17 to 1·34). Evidence of association was highly suggestive (class II) for maternal smoking during pregnancy (OR 1·6, 95% CI 1·45 to 1·76), childhood asthma (1·51, 1·4 to 1·63), maternal pre-pregnancy overweight (1·28, 1·21 to 1·35), and serum vitamin D (WMD -6·93, 95% CI -9·34 to -4·51). INTERPRETATION: Maternal pre-pregnancy obesity and overweight; pre-eclampsia, hypertension, acetaminophen exposure, and smoking during pregnancy; and childhood atopic diseases were strongly associated with ADHD. Previous familial studies suggest that maternal pre-pregnancy obesity, overweight, and smoking during pregnancy are confounded by familial or genetic factors, and further high-quality studies are therefore required to establish causality. FUNDING: None.

9.
BMC Public Health ; 20(1): 1558, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066755

RESUMO

The individual infectiousness of coronavirus disease 2019 (COVID-19), quantified by the number of secondary cases of a typical index case, is conventionally modelled by a negative-binomial (NB) distribution. Based on patient data of 9120 confirmed cases in China, we calculated the variation of the individual infectiousness, i.e., the dispersion parameter k of the NB distribution, at 0.70 (95% confidence interval: 0.59, 0.98). This suggests that the dispersion in the individual infectiousness is probably low, thus COVID-19 infection is relatively easy to sustain in the population and more challenging to control. Instead of focusing on the much fewer super spreading events, we also need to focus on almost every case to effectively reduce transmission.


Assuntos
Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Distribuição Binomial , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/epidemiologia
10.
Aquat Toxicol ; 229: 105579, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33075615

RESUMO

Effective phytoremediation by aquatic plant such as duckweed could be applied to solve Cd pollution. In the present study, the impact of Graphene oxide (GO) on the accumulation of Cd in duckweed has been studied. The response of duckweed was also investigated, concluding growth, Cd2+ flux, and gene expression response. Results showed that GO promoted the accumulation of Cd in duckweed. After 6 h of Cd enrichment in duckweed, Cd content was about 1.4 times that of the control group at fronds and 1.25 times that of the control group at roots, meanwhile, Cd content in the water system was 0.67 times that of the control group. The Cd2+ influx increased significantly. 4471 genes were up-regulated and 3230 genes were down-regulated significantly as duckweed treated with GO under Cd treatment. Moreover, phagosome pathway was downregulated, some key proteins: Stx7, Rab7 and Tubastatin B (TUBB) were significantly downregulated with GO addition under Cd stress. Scanning electron microscope (SEM) observation showed that GO and Cd were attached on the cell surface of duckweed as white crystal. GO could be applied in phytoremediation by duckweed of Cd in aquatic system.

11.
Circ Res ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33086983

RESUMO

Rationale: Changing activity of cardiac CaV1.2 channels under basal conditions, during sympathetic activation, and in heart failure is a major determinant of cardiac physiology and pathophysiology. Although cardiac CaV1.2 channels are prominently up-regulated via activation of protein kinase A, essential molecular details remained stubbornly enigmatic. Objective: The primary goal of this study was to determine how various factors converging at the CaV1.2 I-II loop interact to regulate channel activity under basal conditions, during ß-adrenergic stimulation, and in heart failure. Methods and Results: We generated transgenic mice with expression of CaV1.2 α1C subunits with: 1) mutations ablating interaction between α1C and ß subunits; 2) flexibility-inducing polyglycine substitutions in the I-II loop (GGG-α1C); or 3) introduction of the alternatively spliced 25-amino acid exon 9* mimicking a splice variant of α1C up-regulated in the hypertrophied heart. Introducing three glycine residues that disrupt a rigid IS6-AID helix markedly reduced basal open probability despite intact binding of CaVß to α1C I-II loop, and eliminated ß-adrenergic agonist stimulation of CaV1.2 current. In contrast, introduction of the exon 9* splice variant in α1C I-II loop, which is increased in ventricles of patients with end-stage heart failure, increased basal open probability but did not attenuate stimulatory response to ß-adrenergic agonists when reconstituted heterologously with ß2B and Rad or transgenically expressed in cardiomyocytes. Conclusions: Ca2+ channel activity is dynamically modulated under basal conditions, during ß-adrenergic stimulation, and in heart failure by mechanisms converging at the α1C I-II loop. CaVß binding to α1C stabilizes an increased channel open probability gating mode by a mechanism that requires an intact rigid linker between the ß subunit binding site in the I-II loop and the channel pore. Release of Rad-mediated inhibition of Ca2+ channel activity by ß-adrenergic agonists/PKA also requires this rigid linker and ß binding to α1C.

12.
Aging Clin Exp Res ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025301

RESUMO

Previous studies have reported incidence and mortality declines for colorectal cancer (CRC). We evaluated recent temporal trends of colorectal cancer in the United States for the last 4 decades. Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified primary CRCs diagnosed between 1973 and 2015. Temporal changes were evaluated by 6-year time periods. Age-adjusted incidence rates and annual percentage change (APC) for CRC were calculated by site and gender. Age-standardized relative survival rates were also evaluated. We identified 878,632 CRC patients, 51% of whom were men. For both genders, the proportions of new diagnoses of right-sided colon cancer (RCC) remained relatively stable, with the APC of - 0.8 and - 0.6 for the male and the female, respectively. There was a relative increase in RCC for the younger aged group (< 49 years). In contrast, the proportions of left-sided colon cancer (LCC) and rectosigmoid-cancer (RSC) decreased significantly over time. For those aged 0-49, the age adjusted incidence rates showed a small increase (in both genders), whereas age-adjusted incidence rates declined for those aged 50-64 and > 65 (in both genders). Our study showed near significance in the decline of CRC mortality rates in this population, except the 1-year age-standardized survival of LCC and RSC, and the 5-year age-standardized RCC in females. There was a significant increase in RCC for the younger aged group (< 49 years). In contrast, the proportions of LCC and RSC decreased significantly over time.

13.
Br J Clin Pharmacol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025649

RESUMO

AIMS: Tacrolimus is a critical dose drug and to avoid under-and overexposure, therapeutic drug monitoring is standard practice. However, rejection and drug-related toxicity occur despite whole-blood tacrolimus pre-dose concentrations ([Tac]blood ) being on target. Monitoring tacrolimus concentrations at the target site (within peripheral blood mononuclear cells; [Tac]cells ) may better correlate with drug-efficacy. The aim of this study was to 1) investigate the relationship between [Tac]blood and [Tac]cells , 2) identify factors affecting the tacrolimus distribution in cells and whole-blood, and 3) study the relationship between [Tac]cells and clinical outcomes after kidney transplantation. METHODS: 175 renal transplant recipients were prospectively followed. [Tac]blood and [Tac]cells were determined at month three, six and twelve post-transplantation. Patients were genotyped for ABCB1 1199G>A and 3435C>T, CYP3A4 15389C>T, and CYP3A5 6986G>A. Data on rejection and tacrolimus-related nephrotoxicity and post-transplant diabetes mellitus were collected. RESULTS: Correlations between [Tac]blood and [Tac]cells were moderate to poor (Spearman's r = 0.31; r = 0.41; r = 0.61 at month three, six and twelve, respectively). The [Tac]cells /[Tac]blood ratio was stable over time in most patients (median intra-patient variability 39.0%; range 3.5%-173.2%). Age, albumin and hematocrit correlated with the [Tac]cells /[Tac]blood ratio. CYP3A5 and CYP3A4 genotype combined affected both dose-corrected-[Tac]blood and [Tac]cells . ABCB1 was not significantly related to tacrolimus distribution. Neither [Tac]blood nor [Tac]cells correlated with clinical outcomes. CONCLUSIONS: The correlation between [Tac]blood and [Tac]cells is poor. Age, albumin, and hematocrit correlate with the [Tac]cells /[Tac]blood ratio, whereas genetic variation in ABCB1, CYP3A4 and CYP3A5 do not. Neither [Tac]blood nor [Tac]cells correlated with clinical outcomes.

14.
Int J Infect Dis ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011280

RESUMO

OBJECTIVE: The COVID-19 outbreak in Wuhan, Hubei, China followed the seasonal influenza epidemic. Since COVID-19 may be misdiagnosed as influenza in January 2020, before testing capacity was adequate, it is of significance to study the ratio of influenza cases and COVID-19 cases among influenza-illness-like patients and its temporal pattern. RESULTS: In this study we analyzed the record of the influenza-illness-like patients with a recent travel history to Wuhan arrived in Hong Kong between December 31, 2019 and January 21, 2020. We found that the ratio COVID-19 and influenza is much smaller than a study among ILI in Wuhan. This difference could be due to the difference in sampling. We argue that it is important to consider both samples when inferring number of COVID-19 cases from ILI patients.

15.
Org Lett ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064005

RESUMO

A robust six-membered rhodamine spirocyclic probe 1 containing a versatile 2-aminoimidazolyl moiety was elaborately designed and synthesized via an attractive C-C and C-N coupling strategy to improve the performance in the detection of ultralow transition metal ions. Probe 1 allowed the highly hypersensitive detection of Cu2+ with a superior picomolar limit of detection (35 pM) and nanomolar naked-eye performance (80 nM) via the switching of C-C and C-N cleavage by a catalytic hydrolysis mode.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33048769

RESUMO

Clustering is a fundamental problem that frequently arises in many fields, such as pattern recognition, data mining, and machine learning. Although various clustering algorithms have been developed in the past, traditional clustering algorithms with shallow structures cannot excavate the interdependence of complex data features in latent space. Recently, deep generative models, such as autoencoder (AE), variational AE (VAE), and generative adversarial network (GAN), have achieved remarkable success in many unsupervised applications thanks to their capabilities for learning promising latent representations from original data. In this work, first we propose a novel clustering approach based on both Wasserstein GAN with gradient penalty (WGAN-GP) and VAE with a Gaussian mixture prior. By combining the WGAN-GP with VAE, the generator of WGAN-GP is formulated by drawing samples from the probabilistic decoder of VAE. Moreover, to provide more robust clustering and generation performance when outliers are encountered in data, a variant of the proposed deep generative model is developed based on a Student's-t mixture prior. The effectiveness of our deep generative models is validated though experiments on both clustering analysis and samples generation. Through the comparison with other state-of-art clustering approaches based on deep generative models, the proposed approach can provide more stable training of the model, improve the accuracy of clustering, and generate realistic samples.

17.
J Diabetes Investig ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064907

RESUMO

AIMS/INTRODUCTION: Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease. However, the determination of the autoimmune status of T1DM relies on islet autoantibodies (Abs) as T cell assay is not routinely performed. This study aimed to investigate the diagnostic value of combined assay of islet antigen specific T cells and Abs in T1DM. MATERIALS AND METHODS: Fifty-four patients with T1DM and 56 healthy controls were enrolled. Abs against glutamic acid decarboxylase (GAD), islet antigen-2 and zinc transporter 8 were detected by radioligand assay. Interferon-γ-secreting T cells responding to GAD65 and C-peptide (CP) were measured by enzyme-linked immunospot (ELISPOT). RESULTS: The positive rate for T cell responses was significantly higher in patients with T1DM than that in controls (P<0.001). The combined positive rate of Abs and T cell assay was significantly higher than that of Abs assay alone (85.2% vs. 64.8%, P =0.015). Significant difference in fasting C peptide (FCP) level was found between T+ and T- groups (0.07±0.05 vs. 0.11±0.09 nmol/L, P=0.033). Moreover, levels of FCP and postprandial C peptide (PCP) were both lower in Ab- T+ group than Ab- T- groups (FCP: 0.06±0.05 vs. 0.16±0.12 nmol/L, P=0.041; PCP: 0.12±0.13 vs. 0.27±0.12 nmol/L, P=0.024). CONCLUSIONS: ELISPOT assays in combination with Abs detection could improve the diagnostic sensitivity of autoimmune diabetes.

18.
Materials (Basel) ; 13(20)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066117

RESUMO

In this paper, a series of shear specimens with or without groove were manufactured to mainly analyze the effects of grooves (or shear section height) and steel fibers on the shear properties of concrete with recycled coarse aggregate through double-side direct shear test. In addition, the relationship between the shear strength and the compressive strength and splitting tensile strength of steel fiber reinforced concrete with recycled coarse aggregate (SFRCAC) was also discussed. The experimental results showed that the peak load, deformation corresponding to the peak load and calculated shear strength of the specimens with grooves were lower than those of the specimens without grooves. The steel fiber and recycled coarse aggregate (RCA) had a significant effect on the shear properties of SFRCAC. As the volume content of steel fibers increased, the shear strength of SFRCAC and the corresponding deformation increased gradually. With the replacement ratio of RCA increasing, the shear strength of SFRCAC decreased but the corresponding deformation increased gradually. Finally, the formula for calculating the shear strength of SFRCAC was proposed by analyzing and fitting the test results and the data of related literature.

19.
J Clin Invest ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016929

RESUMO

ARID1A, a component of the chromatin-remodeling complex SWI/SNF, is one of the most frequently mutated genes in human cancer. We sought to develop rational combination therapy to potentiate the efficacy of immune checkpoint blockade in ARID1A-deficient tumors. In a proteomic analysis of a data set from The Cancer Genomic Atlas, we found enhanced expression of Chk2, a DNA damage checkpoint kinase, in ARID1A-mutated/deficient tumors. Surprisingly, we found that ARID1A targets the nonchromatin substrate Chk2 for ubiquitination. Loss of ARID1A increased the Chk2 level through modulating autoubiquitination of the E3-ligase RNF8 and thereby reducing RNF8-mediated Chk2 degradation. Inhibition of the ATM/Chk2 DNA damage checkpoint axis led to replication stress and accumulation of cytosolic DNA, which subsequently activated the DNA sensor STING-mediated innate immune response in ARID1A-deficient tumors. As expected, tumors with mutation or low expression of both ARID1A and ATM/Chk2 exhibited increased tumor-infiltrating lymphocytes and were associated with longer patient survival. Notably, an ATM inhibitor selectively potentiated the efficacy of immune checkpoint blockade in ARID1A-depleted tumors but not in WT tumors. Together, these results suggest that ARID1A's targeting of the nonchromatin substrate Chk2 for ubiquitination makes it possible to selectively modulate cancer cell-intrinsic innate immunity to enhance the antitumor activity of immune checkpoint blockade.

20.
Orthop Surg ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33094562

RESUMO

OBJECTIVE: To explore the hemostatic effect of intra-articular administration of tranexamic acid (TXA) combined with knee flexion in total knee arthroplasty (TKA). METHODS: This randomized controlled trial was conducted at the Third Affiliated Hospital of Southern Medical University (Guangzhou, China) from January 2017 to February 2018. The patients were randomized 1:1 to the TXA group (TXA 500 mg into the joint after closure, knee, and hip flexed at 45° for 4 h) or the control group (physiological saline, with limb fully extended). The primary endpoint was postoperative hemoglobin reduction. The postoperative levels of hemoglobin were measured at four time points: 6 h after operation, and on the first, second, and third postoperative days. Calculated blood loss (CBL) at 3 days, transfusion rate, range of motion (ROM), VAS pain score, and knee circumference increment were the secondary endpoints. Ninety-four (47/group) patients were analyzed. RESULTS: Postoperatively, there were statistically significant differences between the TXA and control groups in CBL (791 ± 212 mL vs 1175 ± 273 mL, P < 0.05). Hemoglobin reduction was significantly lower in the TXA group (2.0 ± 0.9 g/dL vs 4.5 ± 0.7 g/dL, P < 0.05). Based on the transfusion criteria, 3 out of 47 (6.4%) patients in the TXA group and 13 out of 47 (27.6%) patients in the control group received blood transfusions (P = 0.006). ROM (90.8° ± 6.2° vs 87.6° ± 6.4°, P = 0.004), VAS pain score (4.1 ± 1.1 vs 4.8 ± 1.3, P = 0.004), and KCI (2.4 ± 0.9 cm vs 3.2 ± 1.0 cm, P = 0.01) were better in the TXA group compared with thecontrols. There was no deep venous thrombosis (DVT), wound infection or other adverse events in either group. In the control group, 2 patients had a fever after blood transfusion. CONCLUSION: Intra-articular injection of TXA combined with knee and hip flexion at 45° can effectively attenuate CBL and hemoglobin reduction during primary TKA, without an additional adverse event.

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