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1.
BMC Infect Dis ; 21(1): 328, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827456

RESUMO

BACKGROUND: The epidemiology on the human papillomavirus (HPV) among females in Southern China is not well-established. Baseline data on the prevalence of HPV infection in China prior to mass prophylactic HPV vaccination would be useful. Thus, this study aims to determine the type-specific HPV prevalence and distribution among females from Southern China prior to mass HPV vaccination. METHODS: A retrospective cross-sectional study employing 214,715 women attending ChenZhou NO.1 People's Hospital for cervical screening during 2012-2018 was conducted prior to widespread HPV vaccination. HPV genotype was detected using nucleic acid molecular diversion hybridization tests. The overall prevalence, age-specific prevalence, type distribution, and annual trend were analyzed. RESULTS: The overall HPV prevalence was 18.71% (95% confidence interval [CI], 18.55-18.88%) among Southern China females. During 2012-2018, the prevalence of HPV infection showed a downward tendency, from 21.63% (95% CI, 21.07-22.20%) in 2012 to 18.75% (95% CI, 18.35-19.16%) in 2018. Age-specific HPV distribution displayed a peak at young women aged less than 21 years (33.11, 95% CI, 31.13-35.15%), 20.07% (95% CI, 19.70-20.44%) among women aged 21-30 years, 17.29% (95% CI, 17.01-17.57%) among women aged 31-40 years, 17.23% (95% CI, 16.95-17.51%) among women aged 41-50 years, 21.65% (95% CI, 21.11-22.20%) among women aged 51-60 years, and 25.95% (95% CI, 24.86-27.07%) among women aged over 60 years. Of the 21 subtypes identified, the top three prevalent high-risk HPV (HR-HPV) genotypes were HPV52 (5.12%; 95% CI, 21.11-22.20%), - 16 (2.96%; 95% CI, 2.89-3.03%), and - 58 (2.51%; 95% CI, 2.44-2.58%); the predominant low-risk HPV (LR-HPV) genotypes were HPV81 (1.86%; 95%CI, 1.80-1.92%) and - 6 (0.69%; 95% CI, 0.66-0.73%) respectively. Incidence of HR-HPV only, LR-HPV only and mixed LR- and HR-HPV were 15.17, 2.07 and 1.47% respectively. Besides, single HPV infection accounted for 77.30% of all positive cases in this study. CONCLUSIONS: This study highlights 1) a high prevalence of HPV infection among females with a decreasing tendency towards 2012-2018, especially for young women under the age of 21 prior to mass HPV vaccination; 2) HPV52, - 16 and - 58 were the predominant HPV genotypes, suggesting potential use of HPV vaccine covering these HPV genotypes in Southern China.

2.
Heart Surg Forum ; 24(2): E311-E316, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798045

RESUMO

OBJECTIVES: To assess sex differences of clinical presentation and outcomes in propensity-matched patients with acute type A aortic dissection (AAAD). METHODS: We collected the clinical data of patients with AAAD from a single heart center between January 2009 and July 2014. After propensity score matching, we compared differences in clinical presentation and outcomes of patients with AAAD between men and women. RESULTS: There were 590 patients (295 men and 295 women) with AAAD through propensity matching on demographics and patients' history. We found that the presentation and diagnosis of AAAD often were more delayed in women. Severe signs of congestive heart failure (9.8% vs. 5.1%, P = 0.017), cardiac tamponade/shock (9.1% vs. 4.1%, P < 0.001), and periaortic hematoma (26.4% vs. 21.7%, P < 0.001) were more commonly presented in women. Surgery was more commonly performed in men than in women (95.4% (281/295) vs. 91.5% (270/295), P = 0.045), indicating the association of sex with surgical decision. To investigate the association of sex with outcomes after surgery, patients who underwent surgical treatment were re-matched (262 men and 262 women) by propensity score. Women suffered from greater in-hospital mortality than men (8.4% vs. 3.4%, P < 0.001). Postoperative complications of congestive heart failure (9.1% vs. 3.8%, P < 0.001), visceral ischemia (6.8% vs. 1.1%, P < 0.001), and limb ischemia (7.6% vs. 1.5%, P < 0.001) were more frequent in women. For women, prolonged operative time may increase in-hospital mortality, especially after 12 hours from the start of surgery (30.0% vs. 14.3%, P < 0.001). Kaplan-Meier survival analysis indicated worse late outcomes in women in the matched surgery group (log-rank P = 0.012). CONCLUSIONS: Our analysis provides new insights into sex differences in clinical presentation and outcomes of AAAD.

3.
J Glob Health ; 11: 05006, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33828847

RESUMO

Background: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread throughout China. So far, it has caused ~ 4000 deaths in this country. We aimed to systematically characterize clinical features and determine risk factors of sudden death for COVID-19 patients. Methods: Deceased patients with COVID-19 in Tongji hospital from January 22 to March 23, 2020 were extracted. Patients who died within 24 hours after admission were identified as sudden deaths, and the others formed non-sudden deaths. The differences in clinical characteristics between the two groups were estimated. Risk factors associated with sudden deaths were explored by logistic regression. Results: 281 deceased patients were enrolled in this study. Sudden death occurred in 28 (10.0%) patients, including 4 (14.3%) admitted to the intensive care unit. Fatigue was more common in sudden deaths (11, 47.8%) than in non-sudden deaths (40, 17.2%). Both the count and percentage of eosinophils were lower in sudden deaths than that in non-sudden deaths (P = 0.006 and P = 0.004). Compared with non-sudden deaths, sudden deaths had higher plasma levels of procalcitonin, C-reactive protein, D-dimer, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, lactate dehydrogenase, alkaline phosphatase and N-terminal pro-brain natriuretic peptide. There were not significant differences in gender, age, chest CT image features and comorbidities observed. Conclusions: The differences between the two groups suggested more severe systemic inflammation, multi-organ dysfunction, especially impaired liver and heart function in COVID-19 patients who died suddenly after admission. More researches are needed to verify these points.

4.
Nanomaterials (Basel) ; 11(2)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669399

RESUMO

Driving signal reflection on traveling wave electrodes (TWEs) is a critical issue in Mach-Zehnder modulators. Fabrication variation often causes a random variation in the electrode impedance and the signal reflection, which induces modulation characteristics variation. The variation of reflection could be intertwined with the variation of other electrode characteristics, such as microwave signal attenuation, resulting in complexity. Here, we characterize the (partial) correlation coefficients between the reflection and modulation characteristics at different bit rates. Decreasing correlation at higher bit rates is observed. Device physics analysis shows how the observed variation can be related to nanoscale variation of material properties, particularly in the embedded diode responsible for electro-optic modulation. We develop a detailed theory to analyze two variation modes of the diode (P-i-N diode or overlapping P/N regions), which reveal insight beyond simplistic diode models. Microwave signal attenuation tends to reduce the correlation with on-electrode reflection, particularly at high bit rates. The theory shows the relative importance of conductor-induced attenuation and "dielectric"-induced attenuation, with different dependence on the frequency and fabrication variation. Strategies on how to mitigate the effect of variation for better fabrication tolerance are discussed by considering three key factors: pre-shift in structural design, bias condition, and fabrication control accuracy.

5.
Immunotherapy ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781095

RESUMO

Aim: This study explored new immunoadjuvants with stronger immune activity to enhance therapeutic effects against leukemia. Materials & methods: Whole blood and bone marrow of acute myeloid leukemia (AML) patients and healthy volunteers were collected. Isolated mononuclear cells were treated with two newly designed CpG oligodeoxynucleotides, CpG sequence 13 and 19, and known CpG oligodeoxynucleotides and analyzed via flow cytometry. Results: CpG Seq 13 and 19 possess strong immune activation and enhance the proliferation, degranulation and cytotoxicity of T cells. They also inhibit AML cell proliferation. When CpG Seq 13/19 are combined with anti-OX40 antibodies, the cytotoxicity of T cells on AML cells are further enhanced. Conclusion: CpG Seq 13 and 19 are strong immune adjuvant candidates for AML treatment.

6.
FASEB J ; 35(4): e21360, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33749932

RESUMO

The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anti-cytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and in silico molecular docking. An orally available immunotherapeutic-berberine nanomedicine, named NIT-X, has been developed by our group and has shown significantly increased oral bioavailability of berberine, increased IFN-γ production by CD8+ T cells, and inhibition of mast cell histamine release in vivo, suggesting a protective immune response. We further validated the inhibition of replication of SARS-CoV-2 in lung epithelial cells line in vitro (Calu3 cells) by berberine. Moreover, the expression of targets including ACE2, TMPRSS2, IL-1α, IL-8, IL-6, and CCL-2 in SARS-CoV-2 infected Calu3 cells were significantly suppressed by NIT-X. By supporting protective immunity while inhibiting pro-inflammatory cytokines; inhibiting viral infection and replication; inducing apoptosis; and protecting against tissue damage, berberine is a promising candidate in preventing and treating COVID-19 and SARS. Given the high oral bioavailability and safety of berberine nanomedicine, the current study may lead to the development of berberine as an orally, active therapeutic against COVID-19 and SARS.


Assuntos
Antivirais/farmacologia , Berberina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Modelos Biológicos , Vírus da SARS/metabolismo , Síndrome Respiratória Aguda Grave , Administração Oral , /metabolismo , Linhagem Celular , Simulação por Computador , Humanos , Pandemias , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/metabolismo
7.
J Phys Chem Lett ; 12(13): 3335-3342, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33779169

RESUMO

We report the water-mediated charge separation of nitric acid upon incorporation into size-selected Cs+·(HNO3)(H2O)n=0-11 clusters at 20 K. Dramatic spectral changes are observed in the n = 7-9 range that are traced to the formation of many isomeric structures associated with intermediate transfer of the acidic proton to the water network. This transfer is complete by n = 10, which exhibits much simpler vibrational band patterns consistent with those expected for a tricoordinated hydronium ion (the Eigen motif) along with the NO stretching bands predicted for a hydrated NO3- anion that is directly complexed to the Cs+ cation. Theoretical analysis of the n = 10 spectrum indicates that the dissociated ions adopt a solvent-separated ion-pair configuration such that the Cs+ and H3O+ cations flank the NO3- anion in a microhydrated salt bridge. This charge separation motif is evidently assisted by the electrostatic stabilization of the product NO3-/H3O+ ion pair by the proximal metal ion.

8.
J Biochem Mol Toxicol ; : e22746, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661530

RESUMO

Globally, gastric cancer is one of the leading cause of death. Surgical and chemotherapy constitute an important treatment regimen. Unfortunately, less than 20 persons out of 100 patients are live on almost 5 years. Hence, a nontoxic, effective and significantly enhancing novel therapeutic agent is required. d-Carvone is a natural terpenoid present in the essential oils and abundant in the seeds of caraway, as well as known folk medication for diarrhea, acidity, and other gastric disorders. Nevertheless, the role of d-carvone on gastric cancer and its underlying molecular mechanism resides enigmatic. Cells were treated with d-carvone to find out the IC50 by MTT assay. This study shows that 20 and 25 µM d-carvone has induced the reactive oxygen species production and mitochondrial membrane potential in gastric cancer AGS cells, which were evaluated by 2,7-dichlorofluoresceindiacetate and Rh123 staining methods, respectively. The effect of d-carvone against the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway was studied through immunoblotting. Then, we found that it effectively inhibited the proliferation of cell, and the induction of cell apoptosis was scrutinized by dual, 4',6-diamidino-2-phenylindole, and also propidium iodide staining methods. We also explored the fundamental molecular signaling mechanism of the d-carvone and our data depicts that d-carvone induced apoptosis cell death by mitochondrial reactive oxygen species production and downregulation of the and JAK and STAT3 signaling molecules. These overall findings support that the d-carvone inhibits the JAK/STAT3 signaling pathway and induces cell death in the gastric cancer AGS cells.

9.
Int J Cancer ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33751565

RESUMO

Myeloid-derived suppressor cells (MDSCs) play an important role in tumor immune escape. Recent studies have shown that MDSCs contribute to tumor progression under psychological stress, but the underlying mechanism of MDSCs mobilization and recruitment remains largely unknown. In the present study, a chronic restraint stress paradigm was applied to the H22 hepatocellular carcinoma (HCC) bearing mice to mimic the psychological stress. We observed that chronic restraint stress significantly promoted HCC growth, as well as the mobilization of MDSCs to spleen and tumor sites from bone marrow. Meanwhile, chronic restraint stress enhanced the expression of C-X-C motif chemokine receptor 2 (CXCR2) and pErk1/2 in bone marrow MDSCs, together with elevated chemokine (C-X-C motif) ligand 5 (CXCL5) expression in tumor tissues. In vitro, the treatments of MDSCs with epinephrine (EPI) and norepinephrine (NE) but not corticosterone (CORT)-treated H22 conditioned medium obviously inhibited T-cell proliferation, as well as enhanced CXCR2 expression and extracellular signal-regulated kinase (Erk) phosphorylation. In vivo, ß-adrenergic blockade with propranolol almost completely reversed the accelerated tumor growth induced by chronic restraint stress and inactivated CXCL5-CXCR2-Erk signaling pathway. Our findings support the crucial role of ß-adrenergic signaling cascade in the mobilization and recruitment of MDSCs under chronic restraint stress.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33571026

RESUMO

Objective: To evaluate the long-term cost-effectiveness of ginkgolide plus aspirin compared with placebo plus aspirin treatment of ischemic stroke. Background: Stroke is the leading cause of death and long-term disability in China, with high incidence, high mortality, and heavy disease burden. In addition to Western medicines, Chinese clinical guidelines for diagnosis and treatment of acute ischemic stroke recommend application of Chinese patent medicines. Ginkgolide injection is commonly used in the clinical treatment of stroke in China to promote blood circulation and remove blood stasis. The economy of ginkgolide injection needs to be evaluated. Methods: A Markov model was constructed consisting of four disease states: no significant disability, disability, stroke recurrence, and death. Therapeutic data were taken from the Ginkgolide in Ischemic Stroke Patients with Large Artery Atherosclerosis (GISAA) study. Utilities and transition probabilities were extracted from the literature. Cost data were obtained from the China Health Statistics Yearbook and hospital record survey. Expected costs and quality-adjusted life-years (QALYs) of 13 years of cycles (calculated by average age of subjects and Chinese life expectancy) were calculated through TreeAge Pro11 software. The willingness-to-pay (WTP) threshold was set as the Chinese per capita Gross Domestic Product (GDP) in 2019, CN¥70,892/QALY. The results were analyzed by single factor and probability sensitivity analyses. Results: Ginkgolide plus aspirin had a higher expected per-patient cost than placebo plus aspirin but a higher QALYs. Compared with placebo plus aspirin, ginkgolide plus aspirin produced an incremental cost-effectiveness ratio of CN¥14,866.06/QALY, which is below the WTP threshold. Probabilistic sensitivity analysis suggested the acceptability of ginkgolide plus aspirin was higher than that of placebo plus aspirin. Conclusions: The present cost-effectiveness analysis showed that addition of ginkgolides to conventional treatment is cost-effective at a threshold the Chinese per capita GDP.

11.
Neural Plast ; 2021: 8815144, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603780

RESUMO

Purpose: This study is aimed at investigating brain structural changes and structural network properties in complete spinal cord injury (SCI) patients, as well as their relationship with clinical variables. Materials and Methods: Structural MRI of brain was acquired in 24 complete thoracic SCI patients (38.50 ± 11.19 years, 22 males) within the first postinjury year, while 26 age- and gender-matched healthy participants (38.38 ± 10.63 years, 24 males) were enrolled as control. The voxel-based morphometry (VBM) approach and graph theoretical network analysis based on cross-subject grey matter volume- (GMV-) based structural covariance networks (SCNs) were conducted to investigate the impact of SCI on brain structure. Partial correlation analysis was performed to explore the relationship between the GMV of structurally changed brain regions and SCI patients' clinical variables, including injury duration, injury level, Visual Analog Scale (VAS), American Spinal Injury Association Impairment Scale (AIS), International Classification of Functioning, Disability and Health (ICF) scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), after removing the effects of age and gender. Results: Compared with healthy controls, SCI patients showed higher SDS score (t = 4.392 and p < 0.001). In the VBM analysis, significant GMV reduction was found in the left middle frontal cortex, right superior orbital frontal cortex (OFC), and left inferior OFC. No significant difference was found in global network properties between SCI patients and healthy controls. In the regional network properties, significantly higher betweenness centrality (BC) was noted in the right anterior cingulum cortex (ACC) and left inferior OFC and higher nodal degree and efficiency in bilateral middle OFCs, while decreased BC was noted in the right putamen in SCI patients. Only negative correlation was found between GMV of right middle OFC and SDS score in SCI patients (r = -0.503 and p = 0.017), while no significant correlation between other abnormal brain regions and any of the clinical variables (all p > 0.05). Conclusions: SCI patients would experience depressive and/or anxious feelings at the early stage. Their GMV reduction mainly involved psychology-cognition related rather than sensorimotor brain regions. The efficiency of regional information transmission in psychology-cognition regions increased. Greater GMV reduction in psychology region was related with more severe depressive feelings. Therefore, early neuropsychological intervention is suggested to prevent psychological and cognitive dysfunction as well as irreversible brain structure damage.

12.
DNA Cell Biol ; 40(2): 293-302, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33605798

RESUMO

Olfaction is a complicated process that begins with the specific binding of volatile odorant molecules to dedicated olfactory receptors (ORs) in the olfactory epithelium and plays a pivotal role in the survival of mammals. The OR subgenome of the snow leopard has remained largely unexplored, and thus, investigation of the OR system would shed light on the evolutionary dynamics of the snow leopard OR repertoires and genetic evidence for environmental adaptation. In this study, we conducted genome-wide identification and characterization of OR genes in the snow leopard and compared them to all other Panthera species. A total of 213, 294, 624, 305, and 253 functional OR genes were identified in the snow leopard, lion, jaguar, leopard, and tiger, respectively. The phylogenetic relationships of functional Panthera OR genes were illustrated, which comprised 69 families and 350 subfamilies distributed in two classes (Class I and Class II). Comparative analysis of the five Panthera species indicated 115 shared and 5 snow leopard-specific clusters. The potential odorant specificity of certain snow leopard OR genes was identified by similarities to human protein sequences and we identified odorants such as eugenol methyl ether that had the most OR genes. Since our references for odorants were from human studies, possible odorants from snow leopard-specific OR genes need further investigation. The lowest number of OR genes for the snow leopard among Panthera species possibly revealed the association between OR gene family contraction and high-altitude adaptation, which needed further and deeper investigation. This systematic study of OR genes in the snow leopard will provide a solid foundation for further study of olfactory function and variation in the snow leopard.


Assuntos
Cromossomos/genética , Espécies em Perigo de Extinção , Genômica , Panthera , Receptores Odorantes/genética , Sequência de Aminoácidos , Animais , Filogenia , Receptores Odorantes/química
13.
Respir Res ; 22(1): 65, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622325

RESUMO

BACKGROUND: Airway inflammation is a key feature of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroids (ICS) remain the main treatment for airway inflammation. Studies have noted the increased efficacy of ICS and long-acting beta 2 agonist (LABA) combination therapy in controlling exacerbations and improving airway inflammation than either monotherapy. Further studies have suggested that LABAs may have inherent anti-inflammatory potential, but this has not been well-studied. OBJECTIVE: We hypothesize that the LABA olodaterol can inhibit airway inflammation resulting from exposure to respiratory syncytial virus (RSV) via its binding receptor, the ß2-adrenergic receptor. METHODS: Human bronchial epithelial brushing from patients with and without COPD were cultured into air-liquid interface (ALI) cultures and treated with or without olodaterol and RSV infection to examine the effect on markers of inflammation including interleukin-8 (IL-8) and mucus secretion. The cell line NCI-H292 was utilized for gene silencing of the ß2-adrenergic receptor via siRNA as well as receptor blocking via ICI 118,551 and butaxamine. RESULTS: At baseline, COPD-ALIs produced greater amounts of IL-8 than control ALIs. Olodaterol reduced RSV-mediated IL-8 secretion in both COPD and control ALIs and also significantly reduced Muc5AC staining in COPD-ALIs infected with RSV. A non-significant reduction was seen in control ALIs. Gene silencing of the ß2-adrenergic receptor in NCI-H292 negated the ability of olodaterol to inhibit IL-8 secretion from both RSV infection and lipopolysaccharide stimulus, as did blocking of the receptor with ICI 118,551 and butaxamine. CONCLUSIONS: Olodaterol exhibits inherent anti-inflammatory properties on the airway epithelium, in addition to its bronchodilation properties, that is mediated through the ß2-adrenergic receptor and independent of ICS usage.

14.
Soft Matter ; 17(10): 2973-2984, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33595572

RESUMO

During processing, proteins are easily self-assembled into different aggregates, such as nanoparticles and fibrils. Protein aggregates exhibit a strong interfacial activity due to their morphologies and functional groups on the surface. Their interfacial structure and rheological properties at the oil-water interface have a significant effect on the stability and fat digestion of emulsions in food. In this study, ß-lactoglobulin (ß-lg) aggregates including ß-lg nanoparticles (ß-lg NP) and ß-lg fibrils (ß-lg F) were prepared in solution by controlling the heating temperature and pH, and their surface properties including the electric potential, hydrophobicity, and density of free thiol groups were characterized. The adsorption kinetics, interfacial rheology, and displacement by bile salts (BSs) of native ß-lg and its aggregates at the oil (decane)/water interfaces were studied using particle tracking microrheology and dilatational rheology. From the movement of tracer particles at the interface, ß-lg NP and ß-lg F were found to adsorb faster than native ß-lg, and they were found to form interfacial films with a marginally higher elasticity. During the process of protein adsorption, the films of ß-lg and its aggregates are not uniform. In the process of protein displacement, ß-lg NP has the strongest ability while native ß-lg has the weakest ability to resist BS substitution, which is consistent with the results from in vitro digestion experiments. The present study reveals the microrheological behaviour of protein aggregates at the oil-water interface and demonstrates that ß-lg thermal aggregates exhibit an excellent emulsification ability and can be used to control fat digestion. The study also illustrates the applicability of microrheological methods to the study of interfacial rheology and its complementarity with dilatational rheological methods.

16.
J Neurol ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33555418

RESUMO

OBJECTIVE: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. METHODS: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. RESULTS: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). CONCLUSION: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.

17.
Arch Toxicol ; 95(3): 1117-1128, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33474615

RESUMO

N6-Methyladenosine (m6A) is the most prevalent modification of RNA in eukaryotes, and is associated with many cellular processes and even the development of cancers. We hypothesized that single-nucleotide polymorphisms (SNPs) in m6A modification genes, including its "writers", "erasers" and "readers", might affect the m6A functions and associate with the susceptibility to pancreatic ductal adenocarcinoma (PDAC). We first conducted a two-stage case-control study in Chinese population to interrogate all SNPs in 22 m6A modification genes. In the discovery stage, a total of 2735 SNPs were genotyped in 980 patients and 1991 controls. Then, the promising SNP was replicated in another independent population consisting of 858 cases and 2084 controls. As a result, we found the rs7495 in 3'UTR of hnRNPC was significantly associated with increased risk of PDAC in both stages (combined odds ratio = 1.22, 95% confidence interval = 1.12-1.32, P = 2.39 × 10-6). To further reveal the biological function of rs7495 and hnRNPC, we performed a series of biochemical experiments. Luciferase reporter assays indicated that rs7495G allele promoted hnRNPC expression through disrupting a putative binding site for has-miR-183-3p. Cell viability assay demonstrated that knockdown of hnRNPC suppressed the proliferation of PDAC cells. RNA-seq analysis suggested that as an m6A "reader", hnRNPC played an important role in RNA biological processes. In conclusion, our findings elucidated that rs7495G could confer higher risk of PDAC via promoting the expression of hnRNPC through a miRNA-mediated manner. These results provided a novel insight into the critical role of m6A modification in tumorigenesis.

18.
Chemosphere ; 269: 129403, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33385664

RESUMO

Disposal of dredged river sediment requires decreases in both water content for reduction in disposal area, and the amount of eutrophication pollutants at risking of leaching. The effects of CaCl2, polyferric sulfate (PFS) and calcified polyferric sulfate (CaPFS) on dewatering and phosphorus immobilization were examined. Upon CaPFS dosage of 1.88 mg Ca + Fe kg-1 raw sediment (RS) the moisture content of the sediment was 41.1 wt% after pressure filtration, with filtrate dissolved inorganic phosphorus (DIP) of 6.1 mg L-1; better outcomes than for equivalent dosages of CaCl2 or PFS. On CaPFS dosage of 4.98 mg Ca + Fe kg-1 RS, DIP in the filtrate was <0.5 mg L-1. Dosages of CaCl2 and PFS required to achieve <0.5 mg L-1 DIP were 6.79 mg Ca kg-1 RS and 5.64 mg Fe kg-1 RS. CaPFS aids particle surface charge neutralization and sweep flocculation by polymeric iron, improving dehydration efficiency. Synergistic effects of aqueous Ca and Fe promote P stability reducing DIP mobility. For treatment of 10000 m3 of this dredged sediment, CaPFS has the potential to reduce the discharge of eutrophicated water by 74 ± 6% compared with PAC + PAM conditioning, demonstrating the promising application of CaPFS conditioning.


Assuntos
Rios , Poluentes Químicos da Água , Desidratação , Compostos Férricos , Sedimentos Geológicos , Humanos , Fósforo , Poluentes Químicos da Água/análise
19.
BMC Gastroenterol ; 21(1): 43, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509116

RESUMO

BACKGROUND: A series of evidence revealed that body mass index was an important confounding factor in the research of uric acid and ischemic heart disease/hypertension. The objective of this study was to investigate whether obesity status can modify the association between serum uric acid and the severity of liver damage in NAFLD, and the possible interactive effect of hyperuricemia and obesity. METHODS: We conducted a cross-sectional study in a total of 557 ultrasound diagnosed-NAFLD. The hepatic steatosis and liver fibrosis were quantitatively evaluated by transient elastography. Hyperuricemia was defined as serum uric acid > 420 µmol/L in men, > 360 µmol/L in women and obesity was defined as body mass index ≥ 25 kg/m2. The adjusted OR values of hyperuricemia and obesity were analyzed by multivariate logistic regression analysis, and the additive model was used to investigate the possible interactive effect. RESULTS: Multivariate regression analysis showed that hyperuricemia was associated with serious hepatic steatosis (1.74[1.09-2.79]) and elevated ALT (2.17[1.38-3.41]), but not with advanced fibrosis (1.61[0.91-2.85]). The association was further investigated in different BMI group. Hyperuricemia was associated with higher odds of serious hepatic steatosis (2.02[1.14-3.57]) and elevated ALT (2.27[1.37-3.76]) only in obese NAFLD, not in non-obese subjects. Similarly, patients with hyperuricemia had higher odds of advanced fibrosis in obese subjects (2.17[1.13-4.18]), not in non-obese subjects (0.60[0.14-2.70]). Furthermore, there was an additive interaction between hyperuricemia and obesity on the odds of serious hepatic steatosis (AP: 0.39[0.01-0.77]) and advanced fibrosis. (AP: 0.60[0.26-0.95]). CONCLUSIONS: Hyperuricemia and obesity had a significantly synergistic effect on the hepatic steatosis and fibrosis. Thus, management of uric acid may need to be targeted in obese NAFLD.

20.
Soc Sci Med ; 270: 113656, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33401218

RESUMO

Spatial accessibility to medical services (SAMS) is one of the most important indicators to examine the convenience for people to get access to medical services. In China, the difficulty in getting access to medical services is a commonly appreciated social problem. To mitigate this problem, Chinese government established the hierarchical diagnosis and treatment system (HDTS) in 2005. However, there is no existing study to examine the HDTS from the perspective of SAMS. This paper therefore introduces an integrative method to analyze SAMS in adopting HDTS. The introduced integrative method is developed by referring to the existing 2SFCA method, a commonly applied method for analyzing SAMS, and the characteristics of HDTS are taken into consideration. The application of the integrative method is demonstrated with reference to a Chongqing case. The research findings suggest that: 1) A new method to evaluate SAMS in the context of HDTS is needed; 2) The integrative method developed in this study is proven effective for analyzing SAMS in the context of HDTS through the case study; 3) The case results reveal that the implementation of HDTS can significantly improve the overall SAMS performance in Chongqing; 4) The desirable referral rate of HDTS is 1.24% in the case study by comparing the SAMS performance between different referral rates.

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