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1.
Clin Respir J ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33942518

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving pandemic, hypertension is one of the most common co-existing chronic conditions and a risk factor for mortality. Nearly one third of the adult population are hypertensive worldwide, it is urgent to identify the factors that determine the clinical course and outcomes of COVID-19 patients with hypertension. METHODS AND RESULTS: 148 COVID-19 patients with pre-existing hypertension with clarified outcomes (discharge or deceased) from a national cohort in China were included in this study, of whom 103 were discharged and 45 died in hospital. Multivariate regression showed higher odds of in-hospital death associated with high-sensitivity cardiac troponin (hs-cTn) > 28 pg/mL (hazard ratio [HR]: 3.27, 95% confidence interval [CI]: 1.55-6.91) and interleukin-6 (IL-6) > 7 pg/mL (HR: 3.63, 95% CI:1.54-8.55) at admission. Patients with uncontrolled blood pressure (BP) (n = 52) which were defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg for more than once (≥ 2 times) during hospitalization, were more likely to have ICU admission (P=0.037), invasive mechanical ventilation (P=0.028), and renal injury (P=0.005). A stricter BP control with the threshold of 130/80 mmHg was associated with lower mortality. Treatment with renin-angiotensin-aldosterone system (RAAS) suppressors, including angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB) and spironolactone, was associated with lower rate of ICU admission compared to other types of anti-hypertensive medications (8 (22.9%) Vs. 25 (43.1%), P=0.048). CONCLUSION: Among COVID-19 patients with pre-existing hypertension, elevated hs-cTn and IL-6 could help clinicians to identify patients with fatal outcomes at an early stage, blood pressure control is associated with better clinical outcomes, and RAAS suppressors do not increase mortality and may decrease the need of ICU admission.

2.
Brain Behav ; : e02133, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793085

RESUMO

BACKGROUND: Schizophrenia is characterized by several core behavioral features, in which the gastrointestinal symptoms are frequently reported. Maternal immune activation (MIA) has been developed in a rodent model to study neurodevelopmental disorders such as schizophrenia. However, the changes in the gut environment of MIA rats remain largely unknown. METHODS: 10 mg/kg of polyinosinic:polycytidylic acid (Poly I:C) on gestational day 9 was intravenously administered to rats to induce MIA in order to assess changes in behavior, the intestinal barrier and microbiota in offspring. RESULTS: Maternal immune activation offspring shown increased anxiety as indicated by reduced exploration of central area in open field test and decreased exploration of open arms in elevated plus test. Cognitive impairment of MIA offspring was confirmed by reduced exploration of novel arm in Y maze test and deficiency of PPI. Intestinal muscle thickness became thinner and some specific microbial anomalies previously identified clinically were observed in MIA offspring. In addition, an increase of inflammatory responses was found in the gut of MIA offspring. CONCLUSIONS: Maternal immune activation alters behavior, intestinal integrity, gut microbiota and the gut inflammation in adult offspring.

3.
Breastfeed Med ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33913745

RESUMO

Objective: To evaluate the effects of a baby-led self-attachment breastfeeding support intervention on the prevalence and duration of exclusive breastfeeding and nipple pain at 3 days, 6 weeks, 3 months, and 6 months postpartum among Chinese mothers. Materials and Methods: A randomized study was conducted with 504 mother-infant dyads allocated to the baby-led self-attachment breastfeeding support intervention (n = 251) and standard postpartum care (n = 253). Data on the prevalence and duration of exclusive breastfeeding and nipple pain were collected at 3 days, 6 weeks, 3 months and 6 months postpartum. Results: Mothers in the intervention group were significantly more likely exclusively breastfeeding at 3 days (mean difference = 12.1%, 95% confidence interval [CI]: 3.9-20.2%, p = 0.004) and 6 months postpartum (mean difference = 17.8%, 95% CI: 8.3-27.4%, p < 0.001). They were less likely to stop breastfeeding over the 6-month period, compared with the control group (Hazard ratio = 0.65; 95% CI: 0.49-0.87). They were also less likely to experience nipple pain at 3 days (mean difference = -8.1%, 95% CI: -15.9 to -0.4%, p = 0.04) and 3 months postpartum (mean difference = -4.9%, 95% CI: -8.7 to -1.2%, p = 0.01). Conclusions: The baby-led self-attachment breastfeeding support is clinically effective in increasing the prevalence and duration of exclusive breastfeeding and reducing nipple pain among Chinese mothers.

4.
Cell Death Differ ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742136

RESUMO

Small nucleolar RNA SNORD50A and SNORD50B (SNORD50A/B) has been reported to be recurrently deleted and function as a putative tumor suppressor in different types of cancer by binding to and suppressing the activity of the KRAS oncoproteins. Its deletion correlates with poorer patient survival. However, in this study, we surprisingly found that SNORD50A/B loss predicted a better survival in breast cancer patients carrying wild-type p53. Functional studies showed that SNORD50A/B deletion strongly inhibited the proliferation, migration, invasion and tumorigenic potential, and induced cell cycle arrest and apoptosis in p53 wild-type breast cancer cells, while exerted the opposite effects in p53 mutated breast cancer cells. This was also supported by ectopically expressing SNORD50A/B in both p53 wild-type and mutated breast cancer cells. Mechanistically, SNORD50A/B clearly enhances the interaction between E3 ubiquitin ligase TRIM21 and its substrate GMPS by forming a complex among them, thereby promoting GMPS ubiquitination and its subsequent cytoplasmic sequestration. SNORD50A/B deletion in p53 wild-type breast cancer cells will release GMPS and induce the translocation of GMPS into the nucleus, where GMPS can recruit USP7 and form a complex with p53, thereby decreasing p53 ubiquitination, stabilizing p53 proteins, and inhibiting malignant phenotypes of cancer cells. Altogether, the present study first reports that SNORD50A/B plays an oncogenic role in p53 wild-type breast cancers by mediating TRIM21-GMPS interaction.

6.
Front Public Health ; 9: 648172, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681139

RESUMO

Background: Dyslipidemia is a common comorbidity and an important risk factor for myocardial infarction (MI). This study aimed to examine the economic burden of MI combined with dyslipidemia in China. Methods: Patients who were hospitalized due to MI combined with dyslipidemia in 2016 were enrolled. Costs were measured based on electronic medical records and questionnaires. The annual costs were analyzed by conducting descriptive statistics, univariable, and multivariable analyses. Results: Data of 900 patients were analyzed, and 144 patients were dead during the follow-up. The majority of patients were aged 51-70 years (n = 563, 62.55%) and males (n = 706, 78.44%). For all-cause costs, the median annual direct medical costs, direct non-medical costs, indirect costs, and total costs were RMB 13,168 (5,212-29,369), RMB 600 (0-1,750), RMB 676 (0-1,787), RMB 15,361 (6,440-33,943), respectively; while for cardiovascular-related costs, the corresponding costs were RMB 12,233 (3,795-23,746), RMB 515 (0-1,680), RMB 587 (0-1,655), and RMB 14,223 (4,914-28,975), respectively. Lifestyle and complications significantly affected both all-cause costs and cardiovascular-related costs. Conclusions: Increasing attention should be paid to encourage healthy lifestyle, and evidence-based medicine should focus on optimal precautions and treatments for complications, to reduce the economic burden among MI patients with a comorbid dyslipidemia.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33666825

RESUMO

Up to now we have had few evidences on the Non-vitamin K Antagonist Oral Anticoagulants (NOACs)' efficacy and safety in preventing device-related thrombosis (DRT) after percutaneous left atrial appendage closure (LAAC). After LAAC implantation, short-term anticoagulation (NOACs or warfarin) was prescribed. Baseline clinical characteristics, procedural parameters and postoperative follow up data were collected and compared between the two groups. From May 2014 to June 2018, 361 consecutive patients underwent LAAC implantation in our center. 170 patients received warfarin for 45 days at least after LAAC implantation, who were compared with 170 age-matched patients on NOACs. The basic clinical characteristics, as well as procedural parameters were comparable between the two groups, while the NOACs group had higher average CHA2DS2-VASc score (3.3  ±  1.6 vs. 2.9  ±  1.5, P = 0.022*). At 45 days follow up, 289 (86.5%) patients received transoesophageal echocardiography (TEE), and the overall incidence of DRT was 2.4%. The DRT rate was not significantly different between the NOACs and warfarin groups (2.7% vs. 2.1%, P > 0.05), while the NOACs group showed lower all bleeding rate (1.2% vs. 9.0%, P < 0.01). The rates of ischemic stroke as well as major bleeding were comparable between the two groups. Except for 7 DRTs and 1 major peri-device leakage (> 5 mm), anticoagulation was terminated in all other patients. During the follow-up thereafter (mean 868 days), the rates of all-cause death, ischemic stroke and bleeding were comparable between the two groups. Short-term NOACs after LAAC appear to be as effective as warfarin in preventing DRT, with lower bleeding rate.

8.
Am Heart J ; 234: 101-110, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33465369

RESUMO

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.


Assuntos
Angiografia Coronária/métodos , Doença das Coronárias/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Ultrassonografia de Intervenção/métodos , Causas de Morte , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/mortalidade , Doença das Coronárias/patologia , Reestenose Coronária/etiologia , Trombose Coronária/etiologia , Stents Farmacológicos/efeitos adversos , Humanos , Infarto do Miocárdio/etiologia , Revascularização Miocárdica , Estudos Prospectivos
9.
Biosens Bioelectron ; 176: 112931, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33385804

RESUMO

As the urgent need for rapid detection of airborne microbes in a specific environment, a biochip which was integrated with the functions of enrichment and detection was designed and developed. It was composed of cover plate, copper microelectrodes modified with poly-dopamine-co-chitosan (PDA-co-CS) composite gel, sealing washer and substrate containing copper sheet electrode. The microbes were enriched due to the good ventilation efficiency and adhesion of the PDA-co-CS composite gel. The enrichment efficiency of microbes was 99.9%. The electrical impedance spectrum (EIS) test system which was composed of the copper electrodes and the copper sheet electrode were used to detect the concentrated microbes and establish the quantitative detection method of single microbe (S. aureus ATCC 6538) and mixed microbes (S. aureus ATCC 6538, E. coli JM109, and Candida albicans). It was shown that the biochip could respond to the aerosol with 1.26 × 103 cfu/m3S. aureus ATCC 6538, which was 25 times as high as the detection limit of natural deposition method. Meanwhile, the Surface-enhanced Raman Spectrum (SERS) of different microbes were detected in-situ with the help of the silver sol. The SERS data of S. aureus, E. coli and Candida albicans had been analyzed to establish recognition model by the principal component analysis (PCA) method and the three microbes were successfully identified. It was demonstrated that the designed biochip could be applied for separation, enrichment and detection of microbes in the aerosol.

10.
Nanoscale Res Lett ; 16(1): 8, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411061

RESUMO

Periodical silver nanoparticle (NP) arrays were fabricated by magnetron sputtering method with anodic aluminum oxide templates to enhance the UV light emission from ZnO by the surface plasmon resonance effect. Theoretical simulations indicated that the surface plasmon resonance wavelength depended on the diameter and space of Ag NP arrays. By introducing Ag NP arrays with the diameter of 40 nm and space of 100 nm, the photoluminescence intensity of the near band-edge emission from ZnO was twofold enhanced. Time-resolved photoluminescence measurement and energy band analysis indicated that the UV light emission enhancement was attributed to the coupling between the surface plasmons in Ag NP arrays and the excitons in ZnO with the improved spontaneous emission rate and enhanced local electromagnetic fields.

11.
J Exp Clin Cancer Res ; 40(1): 34, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468157

RESUMO

BACKGROUND: BRAFV600E mutation is the most common mutation in thyroid cancer. It strongly activates MAPK/ERK pathway and indicates an invasive subtype of thyroid cancer. PLX4032 is a selective oral inhibitor of the BRAFV600 kinase although with limited effect in treating this panel of thyroid cancer, due to the feedback activation of MAPK/ERK as well as PI3K/AKT pathways. It was investigated that Vitamin C plays a positive role in inhibiting these pathways in thyroid cancer. However, whether Vitamin C could enhance the antitumor effect of PLX4032 remains largely unclear. METHODS: The antitumor efficacy of combination therapy with PLX4032 and Vitamin C on BRAFMT thyroid cancer cell was assessed by the MTT assay, EdU assay and colony formation, Chou-Talalay way was employed to analyze the synergistic effect. Flow cytometry were employed to assess cells' apoptosis and cell cycle arrest in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Western blot and IHC were applied to investigate the mechanism underlying synergistic effect. RESULTS: PLX4032 or Vitamin C monotherapy was mildly effective in treating BRAFMT thyroid cancer cell and xenografts model. The combination therapy significantly inhibited cancer cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest compared to either monotherapy. PLX4032 monotherapy induced feedback activation of MAPK/ERK as well as PI3K/AKT pathway; while combination therapy significantly relieved this feedback. CONCLUSION: Vitamin C promotes the antitumor effect of PLX4032 in BRAFMT thyroid cancer cell and xenografts model via relieving the feedback activation of MAPK/ERK as well as PI3K/AKT pathway. PLX4032/Vitamin C combination may be a potential therapeutic approach to treat BRAFMT thyroid cancer.

12.
Medicine (Baltimore) ; 99(51): e23696, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371113

RESUMO

BACKGROUND: In clinical practices, postoperative fracture patients are often treated with analgesics. As one of the alternative therapies for nondrug analgesia, auricular point pressing has advantages of simple operation, easy to use, no injury and adverse reactions, and great potential for development. In this study, the effect of auricular point pressing therapy on postoperative pain of fracture was objectively evaluated through the method of meta-analysis, so as to provide evidence for clinical applications. METHODS: PubMed, Web of Science, Cochrane Library, EMBASE, Wan fang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, and Chinese Biomedical Literature Database were systematically searched and randomized controlled trials on auricular point pressing in the treatment of postoperative pain after fracture were includes. After independent literature screening, data extraction and quality evaluation by 2 researchers, the original data was retrieved, merged, and analyzed. RevMan 5.3 software was adopted for meta-analysis. RESULTS: This study could provide high-quality evidence to evaluate the effect of auricular point pressing therapy on postoperative pain of fracture. CONCLUSION: This systematic review explored whether auricular point pressing therapy is effective on the intervention of postoperative pain after fracture. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/AZ4JQ.


Assuntos
Auriculoterapia , Fixação Interna de Fraturas , Dor Pós-Operatória/prevenção & controle , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
13.
Coron Artery Dis ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33229940

RESUMO

BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging in contemporary clinical applications. Drug-coated balloon (DCB) angioplasty offers an effective treatment for ISR. Shenqi is a novel iopromide-based paclitaxel-coated balloon and its clinical safety, effectiveness and angiographic efficacy in patients with ISR have not been investigated. METHODS: A total of 216 subjects with the first occurrence of ISR at 11 investigational sites in China were randomly allocated in a 1:1 fashion to treatment with DCB SeQuent Please or Shenqi. Clinical follow-up was planned at 1, 6, 9 and 12 months, and angiographic follow-up was planned at 9 months. The study was powered for the primary endpoint of 9-month in-segment late loss. RESULTS: At 9-month follow-up, the in-segment late loss was 0.29 ± 0.43 mm with Shenqi versus 0.30 ± 0.46 mm with SeQuent Please, and the one-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of Shenqi compared with SeQuent Please (P = 0.002). In total, 12 patients developed target lesion failure (TLF) in the Shenqi group compared with 16 patients in the SeQuent Please group (10.91% versus 15.09%; P = 0.42) within 1 year. TLF was mainly driven by target lesion revascularization (9.09%) followed by target vessel-related myocardial infarction (1.82%) and cardiovascular death (0.91%) in the Shenqi group. CONCLUSIONS: Shenqi DCB was noninferior to SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. Shenqi DCB may become an attractive alternative treatment for patients with coronary ISR, withholding the need for additional stent implantation.

14.
BMC Cardiovasc Disord ; 20(1): 497, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238890

RESUMO

BACKGROUND: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). METHODS: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. RESULTS: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. CONCLUSION: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.

15.
Onco Targets Ther ; 13: 11183-11192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173310

RESUMO

Purpose: Anaplastic thyroid cancer (ATC) is a kind of rare thyroid cancer with very poor prognosis. Doxorubicin has been approved in ATC treatment as a single agent, but monotherapy still shows no improvement of the total survival in advanced ATC. Lenvatinib was investigated with encouraging results in treating patients with radioiodine-refractory differentiated thyroid cancer (DTC). However, antitumor efficacy of combination therapy with lenvatinib and doxorubicin remains largely unclear. Materials and Methods: The antitumor efficacy of combination therapy with lenvatinib and doxorubicin on ATC cell proliferation was assessed by the MTT assay and colony formation. Flow cytometry was employed to assess ATC cells' apoptosis and cell cycle arrest in response to combination therapy. Transwell assay was used to test the migration and invasion in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Results: Lenvatinib monotherapy was less effective than doxorubicin in treating ATC cell lines and xenograft model. The combination therapy of lenvatinib and doxorubicin significantly inhibited ATC cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest as compared to lenvatinib or doxorubicin monotherapy. Conclusion: Lenvatinib promotes the antitumor effect of doxorubicin in ATC cell and xenograft model. The lenvatinib/doxorubicin combination may be a potential candidate therapeutic approach for anaplastic thyroid cancer.

16.
Front Psychiatry ; 11: 559210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173509

RESUMO

Objective: Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamate hypothesis describes one possible pathogenesis of SZ. The solute carrier family 1 gene (SLC1A1) is one of several genes thought to play a critical role in regulating the glutamatergic system and is strongly implicated in the pathophysiology of SZ. In this study, we identify polymorphisms of the SLC1A1 gene that may confer susceptibility to SZ in the Han Chinese population. Methods: We genotyped 36 single-nucleotide polymorphisms (SNPs) using Illumina GoldenGate assays on a BeadStation 500G Genotyping System in 528 paranoid SZ patients and 528 healthy controls. Psychopathology was rated by the Positive and Negative Symptom Scale. Results: Significant associations were found in genotype and allele frequencies for SNPs rs10815017 (p = 0.002, 0.030, respectively) and rs2026828 (p = 0.020, 0.005, respectively) between SZ and healthy controls. There were significant associations in genotype frequency at rs6476875 (p = 0.020) and rs7024664 (p = 0.021) and allele frequency at rs3780412 (p = 0.026) and rs10974573 (p = 0.047) between SZ and healthy controls. Meanwhile, significant differences were found in genotype frequency at rs10815017 (p = 0.015), rs2026828 (p = 0.011), and rs3780411 (p = 0.040) in males, and rs7021569 in females (p = 0.020) between cases and controls when subdivided by gender. Also, significant differences were found in allele frequency at rs2026828 (p = 0.003), and rs7021569 (p = 0.045) in males, and rs10974619 in females (p = 0.044). However, those associations disappeared after Bonferroni's correction (p's > 0.05). Significant associations were found in the frequencies of four haplotypes (AA, CA, AGA, and GG) between SZ and healthy controls (χ 2 = 3.974, 7.433, 4.699, 4.526, p = 0.046, 0.006, 0.030, 0.033, respectively). There were significant associations between rs7032326 genotypes and PANSS total, positive symptoms, negative symptoms, and general psychopathology in SZ (p = 0.002, 0.011, 0.028, 0.008, respectively). Conclusion: The present study provides further evidence that SLC1A1 may be not a susceptibility gene for SZ. However, the genetic variations of SLC1A1 may affect psychopathology symptoms.

17.
Zool Res ; 41(6): 632-643, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-32987454

RESUMO

Accumulating studies have been conducted to identify risk genes and relevant biological mechanisms underlying major depressive disorder (MDD). In particular, transcriptomic analyses in brain regions engaged in cognitive and emotional processes, e.g., the dorsolateral prefrontal cortex (DLPFC), have provided essential insights. Based on three independent DLPFC RNA-seq datasets of 79 MDD patients and 75 healthy controls, we performed differential expression analyses using two alternative approaches for cross-validation. We also conducted transcriptomic analyses in mice undergoing chronic variable stress (CVS) and chronic social defeat stress (CSDS). We identified 12 differentially expressed genes (DEGs) through both analytical methods in MDD patients, the majority of which were also dysregulated in stressed mice. Notably, the mRNA level of the immediate early gene FOS ( Fos proto-oncogene) was significantly decreased in both MDD patients and CVS-exposed mice, and CSDS-susceptible mice exhibited a greater reduction in Fos expression compared to resilient mice. These findings suggest the potential key roles of this gene in the pathogenesis of MDD related to stress exposure. Altered transcriptomes in the DLPFC of MDD patients might be, at least partially, the result of stress exposure, supporting that stress is a primary risk factor for MDD.

18.
Environ Res ; 189: 109919, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32980010

RESUMO

Ionic liquids (ILs) are commonly known as "green" solvents and have been widely used in various fields. However, the ecotoxicity of ILs in aquatic environment has received considerable attention from scientific researchers. This study investigated the toxic effects of different concentrations of 1-octyl-3-methylimidazolium hexafluorophosphate ([C8mim][PF6]) (0, 1.35, 2.70 and 5.40 mg/L) on intestinal physical barrier, immunological barrier, and intestinal microbiome in common carp on days 30 and 60. The results showed that ([C8mim][PF6]) exposure could reduce the intestinal villus height, decrease the mRNA expression of tight junction genes (occludin, claudin-2 and zonula occludens-1), and increase the levels of D-lactic and diamine oxidase, and reduce acid phosphatase and lysozyme activities, complement 3 and 4 contents, and anti-inflammatory cytokine TGF-ß protein level, while increase pro-inflammatory cytokines TNF-α and IL-1ß protein levels in common carp. Moreover, ([C8mim][PF6]) exposure was also found to significantly reduce gut microbial diversity and alter microbial community structure in common carp. Collectively, our study highlighted that exposure to ([C8mim][PF6]) could disrupt intestinal physical barrier, impair immunological barrier and alter intestinal microbiome in common carp, suggesting that ILs exert a negative effect on fish intestinal health status and may pose serious health risks in fish. The results of this study may be helpful to illuminate the toxicity mechanisms of the ILs on fish.

19.
J Geriatr Cardiol ; 17(8): 519-524, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32952527

RESUMO

Previous studies have shown that nicorandil has a protective effect on cardiomyocytes. However, there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction (STEMI) compared to the current standard of percutaneous coronary intervention (PCI) regimen. The CHANGE (China-Admini stration of Nicorandil Group) study is a multicenter, prospective, randomized, double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China, aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocar dial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients.

20.
Signal Transduct Target Ther ; 5(1): 191, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32913191

RESUMO

BRAFV600E is the most common genetic alteration and has become a major therapeutic target in thyroid cancers; however, intrinsic feedback mechanism limited clinical use of BRAFV600E specific inhibitors. Synthetic lethal is a kind of interaction between two genes, where only simultaneously perturbing both of the genes can lead to lethality. Here, we identified CYP2S1 as a synthetic lethal partner of BRAFV600E in thyroid cancers. First, we found that CYP2S1 was highly expressed in papillary thyroid cancers (PTCs) compared to normal thyroid tissues, particularly in conventional PTCs (CPTCs) and tall-cell PTCs (TCPTCs), and its expression was positively associated with BRAFV600E mutation. CYP2S1 knockdown selectively inhibited cell proliferation, migration, invasion and tumorigenic potential in nude mice, and promoted cell apoptosis in BRAFV600E mutated thyroid cancer cells, but not in BRAF wild-type ones. Mechanistically, BRAFV600E-mediated MAPK/ERK cascade upregulated CYP2S1 expression by an AHR-dependent pathway, while CYP2S1 in turn enhanced transcriptional activity of AHR through its metabolites. This AHR/CYP2S1 feedback loop strongly amplified oncogenic role of BRAFV600E in thyroid cancer cells, thereby causing synthetic lethal interaction between CYP2S1 and BRAFV600E. Finally, we demonstrated CYP2S1 as a potential therapeutic target in both BRAFV600E-drived xenograft and transgenic mouse models by targetedly delivering CYP2S1-specific siRNA. Altogether, our data demonstrate CYP2S1 as a synthetic lethal partner of BRAFV600E in thyroid cancers, and indicate that targeting CYP2S1 will provide a new therapeutic strategy for BRAFV600E mutated thyroid cancers.

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