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1.
Acta Cardiol Sin ; 38(1): 47-55, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35068883

RESUMO

Background: A well-functioning cardiopulmonary system, which works as a pump, should generate adequate stroke volume with as little stroke work as possible. We propose a new composite parameter, right ventricular (RV) pump efficiency (η) = left ventricular stroke volume / right ventricular stroke work, to describe this idea in a volume overload population with secundum-type atrial septal defect (ASD). Methods: We consecutively enrolled 50 patients with secundum-type ASD to investigate the relationship between right-sided volume overload and RV pump efficiency. Sixteen patients with a pulmonary to systemic flow ratio (Qp/Qs) > 1.5 underwent implantation of an occluder. The paired t test was used to compare RV pump efficiency before and after ASD closure. Results: RV pump efficiency was inversely correlated with Qp/Qs and was 60 ± 20‰ · mmHg-1 at Qp/Qs = 1. After ASD closure, RV volume, ejection fraction and free wall strain all significantly decreased, while RV pump efficiency significantly increased from 27.4 ± 13.6 to 63.9 ± 20.4‰ · mmHg-1. Conclusions: RV pump efficiency can superiorly reflect the chronicity and severity of secundum-type ASD.

3.
Eur Spine J ; 2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35066683

RESUMO

PURPOSE: To compare the perioperative outcome and operative cost of posterior spinal fusion (PSF) surgery between severe and non-severe Lenke 1 and 2 adolescent idiopathic scoliosis (AIS) patients. METHODS: A total of 509 AIS patients who underwent single-staged PSF between 2013 and 2020 were reviewed. Fifty-four severe scoliosis patients (Cobb angle ≥ 90°) were categorized into Gp1, and 455 non-severe scoliosis (Cobb angle < 90°) patients into Gp2. Propensity score matching (PSM) analysis using one-to-one nearest neighbor matching and match tolerance of 0.001 were performed. Outcome measures were operative time, intraoperative blood loss (IBL), allogeneic transfusion rate, perioperative complication, length of stay, fusion level, number of screws used, postoperative Cobb angle, correction rate (CR), side bending correction index (SBCI) and operative cost. RESULTS: From the PSM analysis, 35 patients from each group were matched. The operative time was 155.9 ± 41.4 and 130.0 ± 30.3 min for Gp1 and Gp2, respectively (p = 0.004). The IBL was 1349.2 ± 1019.0 and 781.9 ± 325.1 mLs for Gp1 and Gp2, respectively (p = 0.003). Fusion level (12.5 ± 0.8 vs. 11.2 ± 1.3, p < 0.001) and number of screws used (16.4 ± 1.6 vs. 14.6 ± 1.4, p < 0.001) were higher in Gp1. Four perioperative complications were observed in Gp1 compared to none in Gp2 (p < 0.039). Gp1 had larger postoperative Cobb angle (p < 0.001), lower CR (p = 0.005) and higher SBCI (p < 0.001). The operative cost was higher in Gp1 (p < 0.001). CONCLUSIONS: Severe Lenke 1 and 2 AIS patients had poorer perioperative outcome, higher complication rate, longer fusion and higher operative cost than non-severe AIS.

4.
Cancer Cell Int ; 22(1): 5, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986865

RESUMO

BACKGROUND: Alternative splicing (AS) plays important roles in transcriptome and proteome diversity. Its dysregulation has a close affiliation with oncogenic processes. This study aimed to evaluate AS-based biomarkers by machine learning algorithms for lung squamous cell carcinoma (LUSC) patients. METHOD: The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database were utilized. After data composition balancing, Boruta feature selection and Spearman correlation analysis were used for differentially expressed AS events. Random forests and a nested fivefold cross-validation were applied for lymph node metastasis (LNM) classifier building. Random survival forest combined with Cox regression model was performed for a prognostic model, based on which a nomogram was developed. Functional enrichment analysis and Spearman correlation analysis were also conducted to explore underlying mechanisms. The expression of some switch-involved AS events along with parent genes was verified by qRT-PCR with 20 pairs of normal and LUSC tissues. RESULTS: We found 16 pairs of splicing events from same parent genes which were strongly related to the splicing switch (intrapair correlation coefficient = - 1). Next, we built a reliable LNM classifier based on 13 AS events as well as a nice prognostic model, in which switched AS events behaved prominently. The qRT-PCR presented consistent results with previous bioinformatics analysis, and some AS events like ITIH5-10715-AT and QKI-78404-AT showed remarkable detection efficiency for LUSC. CONCLUSION: AS events, especially switched ones from the same parent genes, could provide new insights into the molecular diagnosis and therapeutic drug design of LUSC.

5.
Sci Rep ; 12(1): 804, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039542

RESUMO

Obesity is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, 'obesity paradox' is observed in patients with coronary artery disease while defining obesity by body mass index (BMI). The purpose of this study is to identify a better anthropometric parameter to predict cardiovascular events in patients with ASCVD. The study was conducted using the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. A total of 6,920 adult patients with stable ASCVD, enrolled from January 2010 to November 2014, were included, with a mean age of 65.9 years, 73.9% males, and a mean BMI of 26.3 kg/m2 at baseline. These patients were followed up for a median of 2.5 years. The study endpoint was the composite major adverse cardiovascular event (MACE), defined as cardiovascular death, nonfatal myocardial infarction or stroke, or cardiac arrest with resuscitation. Multivariable Cox proportional hazards regression showed a significant positive association between waist-to-BMI ratio and MACE (adjusted hazard ratio 1.69 per cm‧m2/kg increase in waist-to-BMI ratio, 95% CI 1.12-2.49, p = 0.01) after adjusting for potential risk factors and confounders. Traditional anthropometric parameters, such as BMI, weight, waist and waist-hip ratio, or newer waist-based indices, such as body roundness index and a body shape index, did not show any significant linear associations (p = 0.09, 0.30, 0.89, 0.54, 0.79 and 0.06, respectively). In the restricted cubic spline regression analysis, the positive dose-response association between waist-to-BMI ratio and MACE persisted across all the range of waist-to-BMI ratio. The positive dose-response association was non-linear with a much steeper increase in the risk of MACE for waist-to-BMI ratio > 3.6 cm‧m2/kg. In conclusion, waist-to-BMI ratio may function as a positive predictor for the risk of MACE in established ASCVD patients.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35049284

RESUMO

Compartmentalized bioreactions are vital for living cells to regulate biological events since they facilitate isolated yet orchestrated reactions and releases of biological molecules. Engineering bioreactions in compartmentalized droplet bioreactors not only promotes understanding of biological cells but also enhances control in synthetic biology systems. A typical droplet bioreactor is enclosed by impermeable water-in-oil interfaces, which inhibit the reaction rate with the accumulation of aqueous products. This work constructs aqueous two-phase system (ATPS) droplet bioreactors featuring selectively permeable interfaces, which are capable of sequestering reagents in aqueous droplets while constantly releasing products into the aqueous surroundings. Benefiting from this selective permeability, the proposed droplet bioreactor achieves a conversion rate up to 63.2% compared to the 17.9% from the impermeable aqueous-in-oil droplet reactor via coupled reaction-separation. More importantly, it is revealed that uniform aqueous-in-aqueous droplet clusters by microfluidics exhibit an up to 6-fold reaction rate enhancement compared to non-microfluidic ATPS reactors, indicating a unique flow interface effect in droplet clusters. This work offers a new route to allow enzymatic reactions to benefit from efficient flow chemistry via optimized aqueous-aqueous interfaces.

7.
J Environ Sci (China) ; 113: 281-290, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34963537

RESUMO

As the biggest inter-basin water transfer scheme in the world, the South-to-North Water Diversion Project (SNWD) was designed to alleviate the water crisis in North China. The main channel of the middle route of the SNWD is of great concern in terms of the drinking water quality. In this study, we tested the hypothesis that the dissolved organic matter (DOM) derived from the planktonic algae causes the rising levels of CODMn along the middle route by monitoring data on water quality (2015-2019, monthly resolution). The results showed that algal density in the main channel increased along the channel and was significantly correlated with CODMn (p < 0.01). Five fluorescent components of DOM, including tyrosine-like (14.85%), tryptophan-like (22.48%), microbial byproduct-like (26.34%), fulvic acid-like (11.41%), and humic acid-like (24.92%) components, were detected. The level of tyrosine-like components increased along the channel and was significantly correlated with algal density (p<0.01), indicating that algae significantly changed the level of DOM in the channel. Algal decomposition and metabolism were found to be the main mechanisms that drive the changes in CODMn. Therefore, controlling algal density would be an important measure to prevent further increase in CODMn and for the guarantee of excellent water quality.


Assuntos
Qualidade da Água , China , Substâncias Húmicas , Plâncton , Plantas , Espectrometria de Fluorescência
8.
Pathol Res Pract ; 229: 153739, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34920294

RESUMO

OBJECTIVES: To evaluate the expression and differential diagnostic significance of CyclinD1 and D2-40 in follicular neoplasm (FN) and other thyroid adenomatoid lesions. METHODS: A total of 144 cases of thyroid adenomatoid lesions were enrolled. Immunohistochemistry for CyclinD1 and D2-40 was performed. RESULTS: We found two patterns of CyclinD1 expression: nuclear (N) and cytoplasmic (C). The expression of N-CyclinD1 / C-CyclinD1 in FN (77.4%, 48/62; 50.0%, 31/62) was much higher than that in multinodular goiters with dominant nodules (MNG-DN) (16.4%, 10/61; 4.9%, 3/61) (p < 0.05). In contrast, the expression of D2-40 in MNG-DN (82.0%,50/61) was much higher than that in FN (4.8%, 3/62) (p < 0.05). In addition, unique staining patterns were observed: CyclinD1 showed no immunostaining only in all 8 cases of oncocytic cell tumors (OCT); D2-40 staining showed the characteristic wide distribution of lymphatic vessels in all 8 cases of poorly differentiated thyroid carcinoma (PDTC). Finally, the expression of CyclinD1 and D2-40 did not differ among follicular thyroid adenoma and follicular thyroid carcinoma / noninvasive follicular thyroid neoplasm with papillary-like nuclear features (p > 0.05). CONCLUSIONS: CyclinD1 and D2-40 are helpful diagnostic markers of FN, which can assist to discern FN from MNG-DN / OCT / PDTC.

9.
Front Plant Sci ; 12: 740177, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887884

RESUMO

Peach bacterial spot caused by Xanthomonas arboricola pv. pruni (Xap) is a devastating disease worldwide and frequently causes massive economic losses. In recent years, it has become a pandemic outbreak in most peach production areas of China, especially on precocious peaches in the middle reach of the Yangtze River. Rapid, user-friendly detection is extremely important to make the correct diagnosis and develop suitable control strategies. In this study, we described a recombinase polymerase amplification (RPA)/Cas12a-based system that combines RPA and CRISPR/Cas12a for Xap identification. A total of three crRNAs were designed to target a highly conserved ABC transporter ATP-binding protein-encoding gene ftsX to make specific detection of Xap. Results showed that crRNA 2 and crRNA 3 could get consistent detection for Xap. To realize the visualization of detection results, we additionally introduced FQ-reporter and FB-reporter. The developed method was highly sensitive and could detect as low as 10-18 M Xap gDNA with a mini-UV torch, corresponding to 1.63 copies/µl or 8.855 fg/µl gDNA of Xap, while with lateral flow strips, the sensitivity was 10-17 M. In addition, this method could specifically detect Xap from other closely related bacteria or pathogens associated with peach diseases. Furthermore, this method could make correct identification for Xap with crude DNA using NaOH-based extraction (3 min) directly from diseased peach samples. Considering that the developed method could get results within 2 h and could be performed at 37°C (body temperature), it is promising to be applied for Xap diagnosis and monitoring in fields.

10.
Small Methods ; 5(9): e2100747, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34928049

RESUMO

The cellular atlas of the stroma is not well understood. Here, the cell populations in human dental pulp through single-cell RNA sequencing are profiled. Dental pulp stem cells, pulp cells, T cells, macrophages, endothelial cells, and glial cells are identified in human dental pulp. These cells support each other through sending growth signals. Based on the appearance of ligand-receptor pairs between two cell populations, pulp cells have the greatest communication with other cell types, while T cells have the least communication. In addition, T cells expressing TLR1, TLR2, and TLR4, and endothelial cells expressing TLR4, monitor bacterial invasion. These findings provide the census of normal dental pulp.

11.
Ying Yong Sheng Tai Xue Bao ; 32(12): 4212-4222, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951262

RESUMO

There are abundant germplasm resources of drought resistant trees in China. It is difficult for foresters to evaluate and screen excellent germplasm that is suitable for various drought adverse circumstances. In this study, four tree species from different provenances, namely Amygdalus davi-diana, Prunus sibirica, Salix gordejevii, and Caryopteris mongolica, were used as test materials. Four soil regions, namely Dalad Banner, Siziwang Banner, Kouhezi town and Liujiazi town of Kulun Banner in the Central and Eastern Inner Mongolia Autonomous Region were selected as multi-point experiment sites to analyze the growth and physiological status of different tree species and provenances. The additive main effects and multiplicative interaction model was used to evaluate the regional adaptability and stability of the germplasm. The growth and physiological indices of four tree species differed between provenances and locations. Soil conditions (potassium content, nitrogen content, and pH) and climate conditions (annual average temperature, precipitation, and potential evaportranspiration) in different locations all influenced the growth of different provenance species. Concerning tree species, S. gordejevii and C. mongolica are more adapted to the sandy loam and chestnut soil of Dalad Banner and Siziwang Banner. A. davidiana and P. sibirica L. are more adapted to the loess and aeolian sandy soil of Kouhezi town and Liujiazi town. Concerning tree provenances, A. davidiana of Tuzuo, P. sibirica of Ningcheng and Yuanzhou, S. gordejevii of Lanqi, and C. mongolica of Jingbian displayed higher regional stability and better growth adaptability, indicating their suitability for afforestation in similar areas.


Assuntos
Secas , Árvores , Adaptação Fisiológica , China , Clima , Solo
12.
AsiaIntervention ; 7(1): 54-59, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34913003

RESUMO

Aims: The aim of the study was to report the clinical experience, 30-day mortality and acute outcomes of patients undergoing transcatheter aortic valve implantation (TAVI) in the Asia Pacific region. Methods and results: The Asia Pacific TAVI registry is an international, multicentre, prospective, observational registry managed under the auspices of the Asian Pacific Society of Interventional Cardiology (APSIC). Patients undergoing TAVI in seven centres from Hong Kong, Japan, Philippines, Singapore and Taiwan, treated with TAVI devices for severe symptomatic aortic stenosis, were assessed. This first review presents the acute results and 30-day mortality. A multivariable analysis was also performed to identify independent predictors of early all-cause mortality. The enrolment was from 2009 to 2017 and a total of 1,125 patients were recruited. The 30-day mortality rate was 2.5%. Baseline logistic EuroSCORE more than 16 was independently associated with a 2.8-times increased risk of 30-day all-cause mortality (p=0.016). Post-procedural stroke (HR 4.9, p=0.008) was also associated with increased mortality. Conclusions: This initial report of the Asia Pacific TAVI registry demonstrated good acute success and low 30-day mortality. The preprocedural logistic EuroSCORE and post-procedural stroke incidence were strongly associated with acute mortality. Further attempts to reduce post-procedural stroke should be explored.

13.
J Sci Food Agric ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741310

RESUMO

BACKGROUND: Garlic (Allium sativum L.), whose bioactive components are mainly organosulfur compounds (OSCs), is a herbaceous perennial widely consumed as a green vegetable and a condiment. Yet, the metabolic enzymes involved in the biosynthesis of OSCs are not identified in garlic. RESULTS: Here, a full-length transcriptome of purple garlic was generated via PacBio and Illumina sequencing, to characterize the garlic transcriptome and identify key proteins mediating the biosynthesis of OSCs. Overall, 22.56 Gb of clean data were generated, resulting in 454 698 circular consensus sequence (CCS) reads, of which 83.4% (379 206) were identified as being full-length non-chimeric reads - their further transcript clustering facilitated identification of 36 571 high-quality consensus reads. Once corrected, their genome-wide mapping revealed that 6140 reads were novel isoforms of known genes, and 2186 reads were novel isoforms from novel genes. We detected 1677 alternative splicing events, finding 2902 genes possessing either two or more poly(A) sites. Given the importance of serine O-acetyltransferase (SERAT) in cysteine biosynthesis, we investigated the five SERAT homologs in garlic. Phylogenetic analysis revealed a three-tier classification of SERAT proteins, each featuring a serine acetyltransferase domain (N-terminal) and one or two hexapeptide transferase motifs. Template-based modeling showed that garlic SERATs shared a common homo-trimeric structure with homologs from bacteria and other plants. The residues responsible for substrate recognition and catalysis were highly conserved, implying a similar reaction mechanism. In profiling the five SERAT genes' transcript levels, their expression pattern varied significantly among different tissues. CONCLUSION: This study's findings deepen our knowledge of SERAT proteins, and provide timely genetic resources that could advance future exploration into garlic's genetic improvement and breeding. © 2021 Society of Chemical Industry.

14.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1867(2): 159071, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748972

RESUMO

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced and secreted mainly by endothelial cells. Recent studies indicate that ET-1 can regulate lipid metabolism, which may increase the risk of insulin resistance. Our previous studies revealed that ET-1 induced lipolysis in adipocytes, but the underlying mechanisms were unclear. 3T3-L1 adipocytes were used to investigate the effect of ET-1 on lipolysis and the underlying mechanisms. Glycerol levels in the incubation medium and hormone-sensitive lipase (HSL) phosphorylation were used as indices for lipolysis. ET-1 significantly increased HSL phosphorylation and lipolysis, which were completely inhibited by ERK inhibitor (PD98059) and guanylyl cyclase (GC) inhibitor (LY83583). LY83583 reduced ET-1-induced ERK phosphorylation. A Ca2+-free medium and PLC inhibitor caused significant decreases in ET-1-induced lipolysis as well as ERK and HSL phosphorylation, and IP3 receptor activator (D-IP3) increased lipolysis. ET-1 increased cGMP production, which was not affected by depletion of extracellular Ca2+. On the other hand, LY83583 diminished the ET-1-induced Ca2+ influx. Transient receptor potential vanilloid-1 (TRPV-1) antagonist and shRNA partially inhibited ET-1-induced lipolysis. ET-1-induced lipolysis was completely suppressed by CaMKIII inhibitor (NH-125). These results indicate that ET-1 stimulates extracellular Ca2+ entry and activates the intracellular PLC/IP3/Ca2+ pathway through a cGMP-dependent pathway. The increased cytosolic Ca2+ that results from ET-1 treatment stimulates ERK and HSL phosphorylation, which subsequently induces lipolysis. ET-1 induces HSL phosphorylation and lipolysis via the GC/cGMP/Ca2+/ERK/CaMKIII signaling pathway in 3T3-L1 adipocytes.

15.
Bioengineered ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738874

RESUMO

AZD3759 is a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) on the basis of gefitinib and has been proven to enter the central nervous system. Although the promising antitumor effects of AZD3759 on non-small cell lung cancer (NSCLC) have been demonstrated in clinical trials, the regulatory effects of this inhibitor on the antitumor efficacy of radiation (RA) are unclear. The present study aimed to compare the effects of AZD3759 and osimertinib on RA efficacy in NSCLC and explore the potential mechanism of action of AZD3759. We found that the survival in RA-treated NSCLC cells was significantly decreased by treatment with 500 nM AZD3759 and osimertinib at the RA dosage of 8 Gy. The apoptotic rate, cell cycle arrest, and DNA damage in RA-treated NSCLC cells and brain metastasis in RA-treated xenograft nude mice were significantly enhanced by the co-administration of AZD3759 and osimertinib, respectively. In addition, AZD3759 showed a significantly stronger efficacy than osimertinib did. Mechanistically, the receptor tyrosine kinase signaling antibody array revealed that Janus kinase-1 (JAK1) was specifically inhibited by AZD3759, but not by osimertinib. The effects of AZD3759 on RA efficacy in PC-9 cells and in a brain metastasis animal model were significantly abolished by the overexpression of JAK1. Collectively, our results suggested that AZD3759 promoted RA antitumor effects in NSCLC by synergistic blockade of EGFR and JAK1.

16.
Front Immunol ; 12: 767347, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804054

RESUMO

Infection with SARS-CoV-2 triggers the simultaneous activation of innate inflammatory pathways including the complement system and the kallikrein-kinin system (KKS) generating in the process potent vasoactive peptides that contribute to severe acute respiratory syndrome (SARS) and multi-organ failure. The genome of SARS-CoV-2 encodes four major structural proteins - the spike (S) protein, nucleocapsid (N) protein, membrane (M) protein, and the envelope (E) protein. However, the role of these proteins in either binding to or activation of the complement system and/or the KKS is still incompletely understood. In these studies, we used: solid phase ELISA, hemolytic assay and surface plasmon resonance (SPR) techniques to examine if recombinant proteins corresponding to S1, N, M and E: (a) bind to C1q, gC1qR, FXII and high molecular weight kininogen (HK), and (b) activate complement and/or the KKS. Our data show that the viral proteins: (a) bind C1q and activate the classical pathway of complement, (b) bind FXII and HK, and activate the KKS in normal human plasma to generate bradykinin and (c) bind to gC1qR, the receptor for the globular heads of C1q (gC1q) which in turn could serve as a platform for the activation of both the complement system and KKS. Collectively, our data indicate that the SARS-CoV-2 viral particle can independently activate major innate inflammatory pathways for maximal damage and efficiency. Therefore, if efficient therapeutic modalities for the treatment of COVID-19 are to be designed, a strategy that includes blockade of the four major structural proteins may provide the best option.


Assuntos
Antígenos Virais/imunologia , COVID-19/imunologia , Proteínas do Sistema Complemento/imunologia , Sistema Calicreína-Cinina , SARS-CoV-2/imunologia , Proteínas Estruturais Virais/imunologia , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Hemólise , Humanos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/imunologia , Proteínas Recombinantes/imunologia , Proteínas Estruturais Virais/genética
17.
Adv Colloid Interface Sci ; 298: 102562, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34768137

RESUMO

Metal-organic frameworks (MOFs) are as a category of crystalline porous materials. Extensive interest has been devoted to energy storage and energy conversion applications owing to their unique advantages of periodic architecture, high specific surface area, high adsorption, high conductivity, high specific capacitance, and high porosity. One-dimensional (1D) nanostructures have unique surface effects, easily regulated size, good agglutination of the substrate, and other distinct properties amenable to the field of energy storage and conversion. Therefore, 1D nanostructures could further improve the characteristic properties of MOFs, and it is of great importance for practical applications to control the size and morphological characteristics of MOFs. The electrochemical application of 1D MOFs is mainly discussed in this review, including energy storage applications in supercapacitors and batteries and energy conversion applications in catalysis. In addition, various synthesis strategies for 1D MOFs and their architectures are presented.

18.
Cell Mol Biol (Noisy-le-grand) ; 67(2): 132-137, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817327

RESUMO

The objective of this experiment was to observe the allele frequency and genotype distribution of some 9p21 SNPs in the Anhui Han population, and to study its relationship with the susceptibility to ischemic stroke. For this purpose, a collection of 992 patients with ischemic stroke confirmed and hospitalized in our hospital from October 2017 to October 2020 were used as the IS case group, and 951 normal people who had a healthy physical examination in the physical examination center of our hospital during the same period were selected as the control group. After informed consent, cubital venous blood of all subjects was collected, and epidemiological data of the subjects were collected; the rs2383206, rs2383207, rs10757274, and rs1333049 on chromosome 9p21 as the sites to be tested, using Sequenom Mass Array system for genotyping, using Haploview4.2 software to calculate whether the genotype distribution meets Hardy-Weinberg equilibrium. Results showed that there were no significant differences between the two groups in gender, age, and smoking history. There are significant differences in the levels of hypertension, diabetes and hyperlipidemia, total cholesterol, triglycerides, HDL-C and apolipoprotein A1 between the two groups of study subjects. The genotype frequencies of the participating populations were in a balanced state. The results of the association analysis between SNPs and IS susceptibility showed that rs2383207, rs10757274, rs1333049 and rs2383206 are the susceptibility sites of ischemic stroke. It concluded that in Anhui, China, the inheritance of chromosome 9p21 region is associated with ischemic stroke.

19.
Transl Androl Urol ; 10(9): 3620-3627, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733657

RESUMO

Background: To investigate the significance of simultaneous urography of the upper and lower urinary tract of transplanted kidneys combined with computed tomography urography (CTU), computed tomography arteriography (CTA), and computed tomography venography imaging in the planning of open surgery performed to treat any ureteral complications of a transplanted kidney. Methods: In all, 24 patients with ureteral complications after renal transplantation were admitted, 12 of whom had renal graft ostomy during open surgery. Simultaneous antegrade urography of the upper urinary tract and retrograde cystography of the transplanted kidneys were performed on the patients. With the use of computed tomography imaging results, surgical planning was carried out. Results: All surgeries were successfully completed according to preoperative planning. Three patients underwent end-to-end anastomosis of the ureter and bladder muscle flap, 8 patients underwent ureterocystostomy, and 1 patient underwent an end-to-end ureteral anastomosis. After the follow-up up to now, all the patients had stable renal function, and no complications such as ureteral stenosis or urine leakage have thus far reoccurred in the transplanted kidneys. Conclusions: When open surgery is required to treat any ureteral complications following renal transplantation, preoperative multiangle imaging can be used to better understand the condition of the transplanted urinary tract and thus aid considerably in surgical planning.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34675381

RESUMO

The use of positron emission tomography (PET) in early-phase development of novel drugs targeting the central nervous system, is well established for the evaluation of brain penetration and target engagement. However, when novel targets are involved a suitable PET ligand is not always available. We demonstrate an alternative approach that evaluates the attenuation of amphetamine-induced synaptic dopamine release by a novel agonist of the orphan G-protein-coupled receptor GPR139 (TAK-041). GPR139 agonism is a novel candidate mechanism for the treatment of schizophrenia and other disorders associated with social and cognitive dysfunction. Ten healthy volunteers underwent [11C]PHNO PET at baseline, and twice after receiving an oral dose of d-amphetamine (0.5 mg/kg). One of the post-d-amphetamine scans for each subject was preceded by a single oral dose of TAK-041 (20 mg in five; 40 mg in the other five participants). D-amphetamine induced a significant decrease in [11C]PHNO binding potential relative to the non-displaceable component (BPND) in all regions examined (16-28%), consistent with increased synaptic dopamine release. Pre-treatment with TAK-041 significantly attenuated the d-amphetamine-induced reduction in BPND in the a priori defined regions (putamen and ventral striatum: 26% and 18%, respectively). The reduction in BPND was generally higher after the 40 mg than the 20 mg TAK-041 dose, with the difference between doses reaching statistical significance in the putamen. Our findings suggest that TAK-041 enters the human brain and interacts with GPR139 to affect endogenous dopamine release. [11C]PHNO PET is a practical method to detect the effects of novel drugs on the brain dopaminergic system in healthy volunteers, in the early stages of drug development.

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