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1.
Bioorg Chem ; 109: 104717, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33647744

RESUMO

Efforts toward finding potent CDK4 inhibitor for cancer therapy, a series of fluorine substituted pyrrolo[2,3-d]pyrimidine derivatives were designed, synthesized, and evaluated. Among them, the optimal lead compound 18i was discovered with potent activity against CDK4 at the nanomolar level (IC50 = 2.5 nM) and exquisite selectivity which demonstrated only modest activity against 3 out of the 394 protein kinases. 18i exhibited a much greater in vitro antiproliferative activity against several human cancer cell lines than that of the approved drug ribociclib. Further mechanism studies revealed that 18i effectively stimulated cancer cell cycle arrest in G1 phase and induced tumor cell apoptosis. In the comparison of in vivo therapeutic effects in xenograft mouse models of breast cancer, oral administration of 18i showed a significantly better degree of inhibitory effect to ribociclib without obvious toxicity. All of the results indicated that 18i could be a promising CDK4 inhibitor for treating malignancies.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33587716

RESUMO

In this article, we study the leader-following practical attitude consensus problem of a group of multiple uncertain rigid spacecraft systems over jointly connected networks by a distributed event-triggered control law. We first establish a lemma that allows the problem to be converted to a distributed practical stabilization problem of a well-defined uncertain dynamical system. Then, we combine the adaptive distributed observer technique and the adaptive control technique to design an event-triggered adaptive control law and an event-triggered mechanism to solve our problem. The effectiveness of our design is illustrated by a numerical example.

3.
Phytomedicine ; : 153498, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33640247

RESUMO

BACKGROUND: The incidence of nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), has significantly increased in recent years and has become an important public health issue. However, no U.S. Food and Drug Administration (FDA)-approved first-line drug is currently available for the treatment of NAFLD and NASH; therefore, research on new drugs is currently a hot topic. Oroxylum indicum (Linn.) Kurz is extensively distributed in South China and South Asia and has many biological activities. However, its effects on NAFLD or even NASH and the corresponding mechanisms are still not clear. PURPOSE: To investigate the effect and mechanism of O. indicum seed extract (OISE) on preventing anti-inflammatory action in the progression from simple nonalcoholic fatty liver (NAFL) to NASH. METHODS: A network pharmacology method to construct ingredient-target networks and the protein-protein interaction (PPI) network of OISE in NASH were constructed for topological analyses and hub-target screening. Enrichment analyses were performed to identify the critical biological processes and signaling pathways. Simultaneously, in vitro and in vivo experiments investigated the effect and mechanism of OISE, baicalein, and chrysin on inflammation by biochemical indicator detection, luciferase reporters, pathological staining, and immunoblotting in oleic acid-stimulated HepG2 cells or in high-fat diet-fed rats. RESULTS: The network pharmacology showed that OISE prevented the development and progression of NAFL into NASH through various pathways and targets and that the nuclear factor NF-κB (NF-κB) pathway regulated by baicalein and chrysin played an important role in the treatment of NASH. In in vitro experiments, we further showed that OISE and its ingredients, namely, baicalein and chrysin, all improved the inflammatory status in oleic acid-stimulated HepG2 cells, inhibited the nuclear transcriptional activities of NF-κB, increased the IκB level, and decreased the phosphorylation level of NF-κB. Furthermore, in a high-fat diet-induced NASH model in rats, we also showed that OISE prevented the development and progression of NASH by inhibiting the nuclear transcriptional activity of NF-κB. CONCLUSION: OISE suppressed inflammatory responses and prevented the development and progression of NAFL into NASH through inhibition of the nuclear transcriptional activity of NF-κB. OISE may be used to treat NAFLD through many functions, including an increase in insulin sensitivity, a decrease in lipid accumulation in the liver, suppression of inflammation, and clearance of free radicals.

4.
Nanoscale ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471015

RESUMO

The electrode materials of potassium ion storage system have attracted considerable attention given the promising prospect of a potassium ion system in large-scale electrochemical energy storage applications. Despite the excellent anode performance of metal oxides in Li+ and Na+ batteries, the study on their K+ storage performance is still rarely reported. In this study, we report a safe and low-cost strategy to prepare FeOx/N-doped carbons by using NaHCO3 and Fe nanopowder. Benefiting from the oxidation of Fe to Fe3O4, an interesting "one stone, two birds" role of the Fe powder can be identified in the heating process. As a reduction agent, the Fe powder can consume the excess oxygen in the bio-massed carbon framework, facilitating the formation of short-range-ordered domains in the biomass-derived carbon materials (FeOx@GBHCs). Moreover, the close combination of oxidization products (Fe3O4 particles) and carbon matrix leads to numerous FeOx clusters grafted on the surface of the carbon framework via the strong C-O-Fe binding. Therefore, the resultant FeOx/porous carbon exhibits a high reversible capacity of 410 mA h g-1 and an excellent cycling capability. The assembled FeOx@GBHCs//AC potassium-ion hybrid supercapacitor delivers a high energy density of 133 W h kg-1 at a power density of 700 W kg-1, demonstrating a potential prospect of metal oxides in boosting the potassium ion storage performance.

5.
Environ Pollut ; 267: 115613, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254622

RESUMO

Characterizing the interactions between Cd and Zn with respect to the soil soluble Cd and crop Cd uptake allows the development of risk-based approaches to the performance of grain crops. By means of a three-year survey of 358 rice fields and 206 wheat fields across China, this study investigated the effect of Cd-Zn interactions on the phytoavailability of Cd to rice and wheat. The interactive nature between the Cd:Zn ratio and pH of soil affected crop Cd uptake, and the resulting grain Cd intake risk, were examined by the Free-Ion Activity-based model and probability analysis. In highly acidic rice soils (pH < 5.9), soil Zn had no effect on rice Cd uptake, whereas, under near-neutral conditions (pH > 5.9), a site-specific influence of soil Zn on grain Cd concentration was found. Soil Zn could inhibit Cd uptake and translocation by the plant in soil-wheat system when the soil Cd:Zn ratio decreased to 0.0083 and lower. Rice grain poses a significant health risk to local consumers due to its high Cd accumulation and its low Zn accumulation. In order to reduce the health risks from dietary Cd to local consumers, approximately 63.9% of the rice fields and 30.5% of the wheat fields require strategies ameliorating soil acidity in rice soils and increasing Zn concentrations in wheat soils.

6.
Environ Pollut ; 267: 115568, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254717

RESUMO

Previous studies have associated the risk of autism spectrum disorder (ASD) with increased exposures to metals and metalloids such as arsenic. In this study, we used an animal-to-human translational strategy to identify key molecular changes that potentially mediated the effects of arsenic exposures on ASD development. In a previously established rat model, we have induced autistic behaviors in rat pups with gestational arsenic exposures (10 and 45 µg/L As2O3 in drinking water). Neuronal apoptosis and the associated epigenetic dysregulations in frontal cortex were assayed to screen potential mediating pathways, which were subsequently validated with qPCR, western blotting, and immunohistochemistry analyses. Furthermore, the identified pathway, along with serum levels of 26 elements including arsenic, were characterized in a case-control study with 21 ASD children and 21 age-matched healthy controls. In animals, we found that arsenic exposures caused difficulties of social interaction and increased stereotypic behaviors in a dose-dependent manner, accompanied by increased neuronal apoptosis and upregulation of Hipk2-p53 pathway in the frontal cortex. In humans, we found that serum levels of Hipk2 and p53 were 24.7 (95%CI: 8.5 to 43.4) % and 23.7 (95%CI: 10.5 to 38.5) % higher in ASD children than in healthy controls. ASD children had significantly higher serum levels of 15 elements, among which arsenic, silicon, strontium, and vanadium were positively associated with both Hipk2 and p53. Results from both the rat arsenic exposure and human case-control studies suggest a likely role of Hipk2-p53 pathway in ASD development induced by exposures to environmental pollutants such as arsenic.

7.
Seizure ; 84: 40-46, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33278787

RESUMO

PURPOSE: This study aimed to investigate the genetic aetiology in Chinese children diagnosed with status epilepticus (SE). METHODS: Next-generation sequencing, copy number variation (CNV) analysis, and other genetic testing methods were conducted for children with SE lacking an identifiable non-genetic aetiology. Furthermore, the phenotype and molecular data of patients with SE were retrospectively analysed. RESULTS: Among children with SE lacking an identifiable non-genetic aetiology, 73 out of 163 children (44.8 %) were found to have causative variants associated with SE including 66 monogenic mutations in 22 genes and 7 CNVs. Based on the American College of Medical Genetics and Genomics scoring system, the monogenic variants included 64 pathogenic/likely pathogenic and 2 uncertain significance variants. SCN1A gene mutations (n = 32) were the most common cause, followed by TSC2 (n = 5), CACNA1A (n = 5), SCN2A (n = 4), SCN9A (n = 2) and DEPDC5 (n = 2) gene mutations. Sixteen mutations were identified in single genes. Furthermore, 51 (77.3 %) monogenic mutations were de novo. Age at SE onset < 1 year (odds ratio [OR] = 2.70, 95 % confidence interval [CI]: 1.25-5.83, p = 0.012) and co-morbidity of intellectual disability (OR = 3.36, 95 %CI: 1.61-6.99, p = 0.001) were independently associated with pathogenic genetic variants. CONCLUSION: This study identified genetic aetiology in 44.8 % of patients with SE, which indicates a high burden of genetic aetiology among children with SE in China. Our findings highlight the importance for genetic testing of children with SE that lacks an identifiable non-genetic aetiology.

8.
Nano Lett ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33263403

RESUMO

We describe a novel approach for the rational design and synthesis of self-assembled periodic nanostructures using martensitic phase transformations. We demonstrate this approach in a thin film of perovskite SrSnO3 with reconfigurable periodic nanostructures consisting of regularly spaced regions of sharply contrasted dielectric properties. The films can be designed to have different periodicities and relative phase fractions via chemical doping or strain engineering. The dielectric contrast within a single film can be tuned using temperature and laser wavelength, effectively creating a variable photonic crystal. Our results show the realistic possibility of designing large-area self-assembled periodic structures using martensitic phase transformations with the potential of implementing "built-to-order" nanostructures for tailored optoelectronic functionalities.

9.
Am J Mens Health ; 14(6): 1557988320980180, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33342335

RESUMO

We report safety and efficacy of a combination therapy, comprising tamsulosin and phosphodiesterase type 5 inhibitors (PDE5-Is), relative to monotherapy, to ascertain its potential in treating lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) secondary to benign prostatic hyperplasia (BPH) after 3 months' treatment. We screened MEDLINE, EMBASE, and the Cochrane Controlled Trials Register databases, for randomized controlled trials, and obtained eight articles comprising 1144 participants. Results showed that the combination group had superior outcomes with regard to International Prostate Symptom Score (IPSS) and Qmax, compared to the other two groups. The combination group also had superior efficacy with regard to International Index of Erectile Function (IIEF) than the tamsulosin group, but not over the PDE5-Is group. Further, the combination group showed better efficacy in IPSS voiding and quality of life (QoL) compared to the PDE5-Is group. An analysis of safety outcomes revealed extremely high adverse events (AEs) and pain in the combination group. However, therapy discontinuation due to pain and AEs did not increase with increase in AEs. Overall, our findings indicate that a combination of tamsulosin and PDE5-Is is superior to individual tamsulosin and PDE5-Is monotherapy, with regard to improving LUTS and ED secondary to BPH.

10.
Mol Microbiol ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33372330

RESUMO

The recombination of short homologous ends in Escherichia coli has been known for 30 years, and it is often used for both site-directed mutagenesis and in vivo cloning. For cloning, a plasmid and target DNA fragments were converted into linear DNA fragments with short homologous ends, which are joined via recombination inside E. coli after transformation. Here this mechanism of joining homologous ends in E. coli was determined by a linearized plasmid with short homologous ends. Two 3'-5' exonucleases ExoIII and ExoX with nonprocessive activity digested linear dsDNA to generate 5' single-strand overhangs, which annealed with each other. The polymerase activity of DNA polymerase I (Pol I) was exclusively employed to fill in the gaps. The strand displacement activity and the 5'-3' exonuclease activity of Pol I were also required, likely to generate 5' phosphate termini for subsequent ligation. Ligase A (LigA) joined the nicks to finish the process. The model involving 5' single-stranded overhangs is different from established recombination pathways that all generate 3' single-stranded overhangs. This recombination is likely common in bacteria since the involved enzymes are ubiquitous.

11.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(6): 990-999, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33369338

RESUMO

The prevalence of cardiovascular disease in our country is increasing, and it has been a big problem affecting the social and economic development. It has been demonstrated that early intervention of cardiovascular risk factors can effectively reduce cardiovascular disease-caused mortality. Therefore, extensive implementation of cardiovascular testing and risk factor screening in the general population is the key to the prevention and treatment of cardiovascular disease. However, the categories of devices available for quick cardiovascular testing are limited, and in particular, many existing devices suffer from various technical problems, such as complex operation, unclear working principle, or large inter-individual variability in measurement accuracy, which lead to an overall low popularity and reliability of cardiovascular testing. In this study, we introduce the non-invasive measurement mechanisms and relevant technical progresses for several typical cardiovascular indices (e.g., peripheral/central arterial blood pressure, and arterial stiffness), with emphasis on describing the applications of biomechanical modeling and simulation in mechanism verification, analysis of influential factors, and technical improvement/innovation.


Assuntos
Determinação da Pressão Arterial , Pressão Arterial , Fenômenos Biomecânicos , Pressão Sanguínea , Humanos , Reprodutibilidade dos Testes , Fatores de Risco
12.
Acta Trop ; 214: 105762, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33227260

RESUMO

Balantioides coli is a known ciliated zoonotic protozoan that mainly causes diarrhea in humans and pigs. An efficient and reliable culture system for this parasite remains unavailable until now. In this study, a modified Dulbecco's modified eagle medium (DMEM) with pH 7.0-7.5, containing 5 mg/mL starch and 20% new calf serum, was optimized for propagation of B. coli at 28°C-32°C. At the growth-peaking stage, the average trophozoite density was up to 12,970 trophozoites per milliliter. A reproducible protocol for isolation and maintenance of this parasite was also developed based on the modified DMEM culture medium. Moreover, cloning results of B. colipopulations showed that 250 trophozoites in 3 mL modified DMEM medium were the minimal number of trophozoites that propagated to the growth-peaking stage, and finally obtained the individual population. However, less than 250 trophozoites failed to continuously grow in the modified DMEM culture medium under the optimal conditions for growth of B. coli. These data showed that the modified DMEM culture medium is an ideal and efficient medium for propagation and maintenance of B. coli in vitro and will help studies on its biology, genome, transcriptome, proteome, and drug screening.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33186129

RESUMO

Ovarian hyperstimulation syndrome (OHSS) is a rare iatrogenic disorder associated with controlled ovarian stimulation during assisted reproductive technology. Severe OHSS may impose serious complications, including pleural effusion, acute renal insufficiency, venous thrombosis, and even death, although lethal outcomes are rare in forensic practice. The reported incidence of severe OHSS ranges from 0.008% to 10%. Herein, we present the case of a 29-year-old woman who diagnosed with polycystic ovary syndrome and infertility chose to undergo assisted reproduction. She received leuprorelin acetate and follicle stimulating hormone prior to egg retrieval. Three days after the retrieval procedure, she developed abdominal pain and distension. Later that same day, she died unexpectedly. The subsequent autopsy revealed turbid effusions of pleural and peritoneal cavities, abnormal ovarian enlargement, and duskiness of multiple organ surfaces. Microscopic examination disclosed edema and hemorrhage in follicles of both ovaries, thrombosis within the myocardial matrix, and massive pulmonary edema. Routine toxicology screening was negative. The death was attributed to severe OHSS. This case provides a morphologic reference for clinical and forensic work. Autopsy findings in instances of severe OHSS provide valuable insight into the mechanisms and pathogenesis of this disease.

14.
Early Hum Dev ; 152: 105247, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33190019

RESUMO

BACKGROUND: Exposure to prenatal sex steroids as indicated by the ratio of the second to fourth digit length (2D:4D) has been linked to the risk of onset of cancer, while sex steroids may expand the gender disparity in bladder cancer (BC) morbidity. AIM: To explore the association between 2D:4D ratio and BC risk. SUBJECTS: 307 bladder cancer patients and 321 cancer-free individuals. OUTCOME MEASURES: Relationships between 2D:4D and incidence of bladder cancer. RESULTS: For males, a lower 2D:4D ratio of both hands was obtained in the BC group, relative to the control group (left hand: 0.940 ± 0.031 vs. 0.954 ± 0.024, t = -4.72, p < 0.001, Cohen's d = 0.491 and right hand: 0.939 ± 0.031 vs. 0.952 ± 0.022, t = -4.493, p < 0.001, Cohen's d = 0.511). In females, no differences in the 2D:4D ratio were observed between the BC and control groups (p > 0.05). Correlation analysis between 2D:4D ratio and pathological index found no correlation among the BC grade or stage (p > 0.05). CONCLUSION: Men with BC have a lower 2D:4D ratio compared with healthy men. Therefore, having a low 2D:4D ratio is a risk factor for BC in men. Prenatal exposure to sex steroids might play a role in the etiology of BC, which could partially explain the gender disparity in the prevalence of BC.

15.
Vet Parasitol ; 288: 109298, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33171414

RESUMO

Balantioides coli is a ciliated parasite that can cause diarrhea when inhabiting the colon and cecum of pigs and humans. However, information regarding the changes in structure and composition of the gut microbiome in piglets infected with B. coli remains scarce. In this study, 16S rDNA amplicon sequencing was conducted on fecal samples from both B. coli-positive piglets with diarrhea and B. coli-negative piglets without diarrhea. The results showed that Firmicutes and Bacteroidetes were the major phyla in the two groups, and the relative abundance of the phylum Firmicutes, including Ruminococcaceae and Clostridiaceae, was significantly lower in the B. coli-positive samples than in the B. coli-negative ones (p < 0.05). Compared with B. coli-negative samples, Alloprevotella and Faecalibacterium showed distinctly higher relative abundances (p < 0.05) in the B. coli-positive samples, and the abundances of some potential pathogenic bacteria, including Escherichia-Shigella and Campylobacter, were positively correlated with B. coli infection and diarrhea of weaned piglets. In addition, there were statistically significant differences in fecal microbiota diversity and abundances of predicted functional genes between B. coli-colonized and B. coli-negative samples (p <  0.05). Taken together, these findings suggest that there were significant differences in the bacterial community composition, diversity, and functions between the B. coli-positive and B. coli-negative piglets, and the colonization by B. coli may be associated with the dysbiosis of gut microbiota structure in weaned piglets.

16.
Arthritis Rheumatol ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33174383

RESUMO

OBJECTIVE: To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (KOA). METHODS: In this multicenter randomized sham-controlled trial, participants with KOA were randomly assigned to receive electro-acupuncture (EA), manual acupuncture (MA) or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors and statisticians were masked to treatment group assignment. The primary outcome was the response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function at week 8. The primary analysis was analyzed by the Z-test for proportions with the modified intention-to-treat population, which included all randomized participants who have at least one post-baseline measurement. RESULTS: Out of 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91/151), 58.6% (85/145), and 47.3% (69/146) in the EA, MA, and SA groups, respectively. The between-group differences were 13.0% (97.5%CI, 0.2% to 25.9%; P=0.0234) for EA vs SA and 11.3% (97.5%CI, -1.6% to 24.4%; P=0.0507) for MA vs SA. The response rates in EA and MA groups were both significantly higher than the SA group at weeks 16 and 26. CONCLUSION: Among patients with KOA, compared with SA, intensive EA resulted in less pain and better function at week 8 and these effects persisted though week 26. Intensive MA had no benefit for KOA at week 8, although it showed benefits during follow-up.

17.
J Int Med Res ; 48(11): 300060520973915, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233992

RESUMO

OBJECTIVE: This study was performed to evaluate the outcome of complete retroperitoneal laparoscopic nephroureterectomy with bladder cuff excision (RLNU-BCE), which is performed to treat urothelial carcinomas in the renal pelvis or in the ureter higher than the crossing of the common iliac artery without patient repositioning. METHODS: We retrospectively analyzed the clinical data of 48 patients with upper tract urothelial carcinoma who underwent complete RLNU-BCE in our institution from May 2017 to September 2019. RESULTS: RLNU-BCE was successfully performed in all 48 patients. The median operation time was 110 minutes [interquartile range (IQR), 100-130 minutes], and the median postoperative anesthesia recovery time was 10 minutes (IQR, 7-15 minutes). The median postoperative hospitalization period was 5 days (IQR, 4-6 days). Pathologic examination revealed that the margin of all resected specimens was negative. After a median follow-up of 13 months (IQR, 7-20 months), no local recurrence or distant metastasis was found. No complications occurred during follow-up. CONCLUSION: Based on our experience with this technique, RLNU-BCE deserves application and promotion in clinical practice. Long-term comparative studies are required to confirm its superiority over other techniques.

18.
Front Oncol ; 10: 541390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072572

RESUMO

Background and objective: Radical cystectomy has been characterized as the most difficult operation in urology because of the complex surgical procedures and postoperative complications. Enhanced recovery after surgery (ERAS), which reduces the incidence of perioperative complications, has been widely used in clinical surgery. Herein, we performed a meta-analysis to evaluate the efficacy and safety of ERAS vs. conventional recovery after surgery (CRAS) on perioperative outcomes of radical cystectomy. Methods: We performed a systematic search of randomized controlled trials (RCTs) in the following databases: Medline, Embase, and the Cochrane Controlled Trials Register, based on the PICOS strategy. The reference lists of the retrieved studies were further surveyed for relevant publications. Results: Our search yielded seven RCTs containing 813 patients. The ERAS group was found to have better performance in the following parameters: length of hospital stay [mean difference (MD) = -1.12, 95% confidence interval (CI): -1.80 to -0.45, P = 0.001], time to first flatus (MD = -0.70, 95% CI: -0.98 to 0.41, P < 0.00001), and time to regular diet (MD = -0.12, 95% CI: -1.76 to -0.28, P = 0.007). However, there were no significant differences between the two groups in major complications [odds ratio (OR) = 0.91, 95% CI: 0.63 to 1.34, P = 0.64], readmission (OR = 1.15, 95% CI: 0.65 to 2.01, P = 0.63), ileus (OR = 0.75, 95% CI: 0.44 to 1.28, P = 0.29), wound infection (OR = 0.56, 95% CI: 0.31 to 1.01, P = 0.05), mortality (OR = 0.69, 95% CI: 0.24 to 1.99, P = 0.49), or time to first bowel movement (MD = -0.55, 95% CI: -1.62 to 0.53, P = 0.32). Conclusion: ERAS reduced the length of hospital stay, time to first flatus, and time to regular diet after cystectomy. Compared to CRAS protocols, ERAS protocols do not increase the risk of adverse events.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33118183

RESUMO

BACKGROUND: Left bundle branch area pacing (LBBAP) is an innovative pacing technology, which needs further study. METHODS: 70 LBBAP patients with intrinsic QRS duration (QRSd) less than 120 ms were consecutively enrolled in our center. According to whether the left bundle branch potential (LBBp) was recorded or not, the patients were divided into the potential positive group (LBBAP+) and the potential negative group (LBBAP-). Electrocardiographic and echocardiographic parameters were used to evaluate electrical and mechanical characteristics. Lead parameters and complications were followed up. RESULTS: There were 52 patients in LBBAP+ and 18 patients in LBBAP-. The QRSd and the left ventricular activation time (LVAT) were wider after LBBAP. QRSd showed no significant difference between LBBAP+ and LBBAP-. LVAT was significantly shorter in LBBAP+ than in LBBAP-. Frontal QRS axis shifted leftward and the V1 morphologies changed after LBBAP. QRS axis and V1 morphologies showed no significant differences between two groups. Paced R-wave transition moved forward compared with intrinsic R-wave transition in both groups. Peak systolic strain of left ventricle (LVPSS) increased and peak systolic dispersion of left ventricle (LVPSD) did not change significantly after LBBAP. Systolic and diastolic function as well as mechanical synchronism had no significant differences between two groups. LBBAP had great pacing parameters. CONCLUSION: LBBAP changes electrical and mechanical characteristics and has good safety in patients with normal intrinsic QRSd. LBBAP+ and LBBAP- show no significant differences in mechanical synchronization and interventricular electrical synchronization. The LBBAP+ shows better left ventricular electrical synchronicity. This article is protected by copyright. All rights reserved.

20.
J Ethnopharmacol ; : 113462, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058924

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Tongmai Yangxin pill (TMYX) is derived from the Zhigancao decoction recorded in Shang han lun by Zhang Zhongjing during the Han dynasty. TMYX is used for the clinical treatment of chest pain, heartache, and qi-yin-deficiency coronary heart disease. Previous studies have confirmed that TMYX can improve vascular endothelial function in patients with coronary heart disease by upregulating nitric oxide activity and then regulating vascular tension. Whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels remains unclear. AIM OF THE STUDY: This study aimed to reveal whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels. The underlying cAMP/PKA and NO-cGMP signaling pathway-dependent mechanism is also explored. MATERIALS AND METHODS: The left anterior descending coronary arteries of healthy adult male SD rats were ligated to establish the NR model. TMYX (4.0 g/kg) was orally administered throughout the experiment. Cardiac function was measured through echocardiography. Thioflavin S, Evans Blue, and TTC staining were used to evaluate the NR and ischemic areas. Pathological changes in the myocardium were assessed by hematoxylin-eosin staining. An automated biochemical analyzer and kit were used to detect the activities of myocardial enzymes and myocardial oxidants, including CK, CK-MB, LDH, reactive oxygen species, superoxide dismutase, malonaldehyde, and NO. The expression levels of genes and proteins related to the cAMP/PKA and NO/cGMP signaling pathways were detected via real-time fluorescence quantitative PCR and Western blot analysis, respectively. A microvascular tension sensor was used to detect coronary artery diastolic function in vitro. RESULTS: TMYX elevated the EF, FS, LVOT peak, LVPWd and LVPWs values, decreased the LVIDd, LVIDs, LV-mass, IVSd, and LV Vols values, demonstrating cardio-protective effects, and reduced the NR and ischemic areas. Pathological staining showed that TMYX could significantly reduce inflammatory cell number and interstitial edema. The activities of CK, LDH, and MDA were reduced, NO activity was increased, and oxidative stress was suppressed after treatment with TMYX. TMYX not only enhanced the expression of Gs-α, AC, PKA, and eNOS but also increased the expression of sGC and PKG. Furthermore, TMYX treatment significantly decreased ROCK expression. We further showed that TMYX (25-200 mg/mL) relaxed isolated coronary microvessels. CONCLUSIONS: TMYX attenuates myocardial NR after ischemia and reperfusion by activating the cAMP/PKA and NO/cGMP signaling pathways, further upregulating NO activity and relaxing coronary microvessels.

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