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1.
Medicine (Baltimore) ; 100(18): e25742, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950958

RESUMO

BACKGROUND: The pathogenesis of chronic fatigue syndrome (CFS) is not clear. The main purpose of treatment is to improve autoimmune function and relieve fatigue symptoms. Moxibustion is often used to treat diseases caused by low autoimmunity, especially in relieving fatigue symptoms. It is a superior therapy for CFS in traditional Chinese medicine. At present, there is a lack of the high level clinical evidence to support the moxibustion in the treatment of CFS, so this study will systematically review and analyze the currently available randomized controlled trials to evaluate the efficacy and safety of moxibustion in the treatment of CFS. METHODS: We will systematically search PubMed, EMBASE, Cochrane library, Sinomed, CNKI, VIP, and Wanfang Database, ClinicalTrials.gov and Chinese Clinical Trial Registry will also be searched. The time range for the search will be from database activation to March 31, 2021. The randomized controlled trials (RCTs) associated with moxibustion for CFS will be included, regardless of language.We will use the standard proposed in Cochrane Handbook 5.1.0 to assess the bias risk of a single RCT. The main outcome index of the study is Fatigue Assessment Instrument (FAI), secondary outcome indexes will include Fatigue Scale -14 (FS-14), Fatigue Severity Scale (FSS), Pittsburgh sleep quality index (PSQI), natural killer (NK) cells, interleukin- 2 (IL-2), T lymphocyte subsets (CD4+, CD8+), cure rate, total efficiency and adverse reactions. The random effect model meta was used to analyze the effect data of a single RCT. Heterogeneity will be measured by Cochran Q test and I-squared statistics. We will use 2 subgroup analyses to explore the source of heterogeneity. RCTs with high bias risk was excluded and adjustment effect model was used for sensitivity analysis to test the robustness of the meta-analysis results. The publication bias included in RCTs will be assessed by funnel plot and Egger test. RESULTS: This study will objectively and comprehensively evaluate the efficacy and safety of randomized controlled trials of moxibustion in the treatment of chronic fatigue syndrome, and the results will be submitted to peer-reviewed journals for publication. CONCLUSION: This systematic review will provide clinicians with the latest high-quality evidence for the use of moxibustion in the treatment of chronic fatigue syndrome. INPLASY REGISTRATION NUMBER: INPLASY202140063.

2.
J Pharm Pharmacol ; 73(4): 425-436, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33793828

RESUMO

OBJECTIVES: Hypericin is a polycyclic aromatic naphthodianthrone that occurs naturally. It is also an active ingredient in some species of the genus Hypericum. Emerging evidence suggests that hypericin has attracted great attention as a potential anticancer drug and exhibits remarkable antiproliferative effect upon irradiation on various tumour cells. This paper aims to summarise the anticancer effect and molecular mechanisms modulated by hypericin-medicated photodynamic therapy and its potential role in the cancer treatment. KEY FINDINGS: Hypericin-medicated photodynamic therapy could inhibit the proliferation of various tumour cells including bladder, colon, breast, cervical, glioma, leukaemia, hepatic, melanoma, lymphoma and lung cancers. The effect is primarily mediated by p38 mitogen-activated protein kinase (MAPK), JNK, PI3K, CCAAT-enhancer-binding protein homologous protein (CHOP)/TRIB3/Akt/mTOR, TRAIL/TRAIL-receptor, c-Met and Ephrin-Eph, the mitochondria and extrinsic signalling pathways. Furthermore, hypericin-medicated photodynamic therapy in conjunction with chemotherapeutic agents or targeted therapies is more effective in inhibiting the growth of tumour cells. SUMMARY: During the past few decades, the anticancer properties of photoactivated hypericin have been extensively investigated. Hypericin-medicated photodynamic therapy can modulate a variety of proteins and genes and exhibit a great potential to be used as a therapeutic agent for various types of cancer.

3.
Adv Mater ; : e2008424, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33876466

RESUMO

The propensity of Zn-metal anodes to form non-uniform or dendritic electrodeposits is bound up with the nature of the electrode surface. However, the effect of surface structure on the inherent nucleation and deposition of Zn is not yet well understood. Here, the surface structure of a Zn-metal anode is reconstructed with Sn-crystal textures via a facile chemical displacement reaction. Compared to the bare Zn, the high-affinity Zn binding sites of Sn afford lower deposition energy barrier, which promotes deposition kinetics. What is more, a Sn-textured surface with moderate Zn affinity but high average surface energy ensures a better wettability from the deposits, leading to the lateral growth of Zn crystals. The resultant Sn-textured Zn-metal anode exhibits an extremely low voltage hysteresis of 20 mV and achieves a prolonged cycling stability over 500 h cycles without dendrite formation. This work provides new insights into the crystal-texture-dependent Zn electrodeposition process and offers direction for direct surface texturing to better stabilize Zn-metal anodes with improved reversibility.

4.
Medicine (Baltimore) ; 100(17): e25596, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907110

RESUMO

BACKGROUND: As the most common type of cerebrovascular disease, ischemic stroke is the disturbance of cerebrovascular circulation caused by various factors, with complex pathogenesis. At present, the molecular mechanism of ischemic stroke is still unclear, and there lacks early diagnostic markers. Therefore, there is an urgent need to find effective preventive measures, active diagnostic methods and rapid treatment measures. In recent years, related studies have displayed that long noncoding RNAs (lncRNAs) is related to the prognosis of ischemic stroke. However, the results are not supported by some evidence. Therefore, in this study, meta-analysis was used to analyze the relationship between lncRNAs and the prognosis of ischemic stroke. In addition, we carried out bioinformatics analysis to study the action mechanism and related pathways of lncRNAs in ischemic stroke. METHODS: Literature search was operated on databases up to March 2021, including China National Knowledge Infrastructure, Chinese Biomedical literature Database, Chinese Scientific and Journal Database, Wan Fang database, Web of Science, PubMed, and EMBASE. The relationship between lncRNAs expression and survival outcome was estimated by hazard ratio (HR) and 95% confidence interval (CI). Meta-analysis was conducted on the Stata 16.0. Starbase v2.0 software predicts microRNAs (miRNAs) that interacts with lncRNAs. In addition, HMDD v2.0 database filters out miRNAs related to ischemic stroke. Furthermore, Consite transcription factor database was used to predict the transcription factors of each lncRNAs and miRNA. At the same time, the transcription factors related to ischemic stroke were screened out after intersection. miRwalk online software was applied to predict the target mRNA of each miRNA, and the common target genes were screened by consistent method. The molecular regulatory network map of lncRNAs in ischemic stroke was drawn. Based on the overlapping target genes, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analysis were carried out to explore the possible mechanism. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This study will provide evidence-based medical evidence for the relationship between lncRNA and the prognosis of ischemic stroke. What is more, bioinformatics analysis will provide ideas for the study of ischemic stroke mechanism. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/QBZW6.


Assuntos
Biologia Computacional/métodos , RNA Longo não Codificante/sangue , Biomarcadores/sangue , Bases de Dados Genéticas , Ontologia Genética , Humanos , /mortalidade , Metanálise como Assunto , MicroRNAs/sangue , Prognóstico , Modelos de Riscos Proporcionais , Mapeamento de Interação de Proteínas , Projetos de Pesquisa , Análise de Sobrevida , Fatores de Transcrição/sangue
5.
Bioorg Chem ; 112: 104830, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33819736

RESUMO

Fourteen new monoterpene-flavonoid conjugates including four monoterpene-conjugated chalcones (glabratins A-D, 1-4), seven monoterpene-conjugated dihydrochalcones (glabratins E-K, 5-11), and three monoterpene-conjugated flavanones (glabratins L-N, 12-14), together with four known analogues (15-18) were isolated from the aerial parts of Sarcandra glabra. The structures and the absolute configurations of these compounds were elucidated by the spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1, 4-6, 9-14, and 18 showed obvious cell autophagy-inducing activities at 25 µM in HEK293 cells. Furthermore, the bioassay results also showed that 18 induced cell autophagy in a dose dependent manner. Our findings revealed a rare class of monoterpene-flavonoid conjugates in nature and firstly reported their autophagy-inducing activities.

6.
ACS Infect Dis ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33834753

RESUMO

Carbapenem-resistant Klebsiella pneumoniae has been classified as an Urgent Threat by the Centers for Disease Control and Prevention (CDC). The combination of two "old" antibiotics, polymyxin and chloramphenicol, displays synergistic killing against New Delhi metallo-ß-lactamase (NDM)-producing K. pneumoniae. However, the mechanism(s) underpinning their synergistic killing are not well studied. We employed an in vitro pharmacokinetic/pharmacodynamic model to mimic the pharmacokinetics of the antibiotics in patients and examined bacterial killing against NDM-producing K. pneumoniae using a metabolomic approach. Metabolomic analysis was integrated with an isolate-specific genome-scale metabolic network (GSMN). Our results show that metabolic responses to polymyxin B and/or chloramphenicol against NDM-producing K. pneumoniae involved the inhibition of cell envelope biogenesis, metabolism of arginine and nucleotides, glycolysis, and pentose phosphate pathways. Our metabolomic and GSMN modeling results highlight the novel mechanisms of a synergistic antibiotic combination at the network level and may have a significant potential in developing precision antimicrobial chemotherapy in patients.

7.
Adv Mater ; : e2008668, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33837605

RESUMO

The evolution of polygonal-shaped nanoholes on the (100) surface of germanium, aided by focused ion beam induced self-organization, is presented. The energetic beam of ions creates a viscous phase which, at a thermodynamical minimum, leads to surface self-organization. A directed viscous-flow along the predefined nanoholes provides well-ordered polygonal nanostructures, ranging from triangles to hexagons and octagons, as desired. The amorphization exhibiting a confined viscous-flow at the walls of nanoholes is attributed to the localized melting zones induced by site-specific thermal spikes during ion irradiation, as revealed by microscopy and molecular dynamics studies. This leads to a local self-organization in the vicinity of each circular nanohole via a viscous-fingering process at the nanoscale. Such controlled self-organization, with the help of a predefined scanning grid, transforms the circular holes into the desired polygonal shape. The present morphology manipulation promises to surmount the barriers concerning the size reduction efforts in the field of nanofabrication.

8.
Endocr Connect ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794504

RESUMO

OBJECTIVE: Prolactin (PRL) has been demonstrated as a metabolic hormone to regulate energy metabolism recently. The present study aims to investigate the association between PRL and metabolic alterations in different obesity phenotypes. METHODS: A total of 451 drug-naive participants were recruited, comprising 351 obese patients and 100 age- and sex-matched healthy participants with normal weight. PRL, anthropometric, and clinical parameters were measured. RESULTS: In the obesity group, 15.1% (53/351) were categorized as 'metabolically healthy obesity (MHO)'. Besides favorable blood pressure, glucose, and lipids profiles, the MHO group exhibited increased PRL, and lower levels of high-sensitivity C-reactive protein (hsCRP), homeostasis model assessment of insulin resistance (HOMA-IR), and adipose tissue insulin resistance (adipo-IR) than the metabolically unhealthy obesity (MUHO) group (PRL, HOMA-IR, and adipo-IR: P < 0.01; hsCRP: P < 0.05). The severe MUHO group showed significantly decreased PRL levels than the mild MUHO group (P < 0.05). Multivariate linear regression analysis indicated that fasting plasma glucose (FBG) and adipo-IR were significantly associated with PRL (FBG: ß = -0.263, P < 0.05; adipo-IR: ß = -0.464, P < 0.01). Multivariable logistic regression analysis showed that hsCRP (OR = 0.824) and PRL (OR = 1.211) were independent predictors of MHO (all P < 0.01). CONCLUSION: The MHO group had significantly increased circulating PRL levels when compared with the control and MUHO groups, and multivariable logistic regression analysis showed that PRL was independent predictors of MHO. Our findings suggested that increased circulating PRL might be a compensatory response for favoring energy metabolism during obesity.

9.
J Transl Med ; 19(1): 176, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910562

RESUMO

BACKGROUND: Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF. METHODS: This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group. RESULTS: The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts. CONCLUSIONS: The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx.

10.
Molecules ; 26(8)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924385

RESUMO

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-ß2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-ß2 serum levels, while TGF-ßRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-ß2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

11.
BMC Med Inform Decis Mak ; 21(1): 132, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33874943

RESUMO

BACKGROUND: Previous studies showed that transitional care reduces the complication rate and readmission rate and improves the quality of life in kidney transplant receipts, nevertheless, in fact there are no standard evaluation indexes and debatable scientific of existing indexes in kidney transplant recipients. Therefore, the aim of this study was to construct an evaluation index system to assess the effects of transitional care in kidney transplant recipients. METHODS: Based on Omaha system, an initial evaluation index system about the effects of transitional care in kidney transplant recipients was drafted by the literature review and semi-structured interview. Two rounds of correspondence were conducted in 19 experts and the analytic hierarchy process (AHP) was used to calculate the weights of all indexes. RESULTS: Five first-level indexes, sixteen second-level indexes, and forty-eight third-level indexes were selected in the initial evaluation index system. The authority coefficient of two-round expert consultations was 0.90 and coordination coefficients of indexes ranged from 0.24 to 0.34. CONCLUSION: The established evaluation index system for the effectiveness of transitional care for kidney transplant recipients was scientific and reliable. Furthermore, it would be a potential method to evaluate effects of transitional care in kidney transplant recipients after further examination.


Assuntos
Transplante de Rim , Cuidado Transicional , Técnica Delfos , Humanos , Qualidade de Vida
12.
Cancer Res ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653774

RESUMO

Hepatitis B-associated hepatocellular carcinoma (HCC) is often accompanied by severe vascular invasion and portal vein tumor thrombus leading to a poor prognosis. However, the underlying mechanism of this disease remains obscure. In this study, we demonstrate that the hepatitis B virus (HBV)-encoded gene HBx induces high IL-8 production through MEK-ERK signal activation, leading to enhanced endothelial permeability to facilitate tumor vascular invasion. In a vascular metastatic model using a tail vein injection in a transgenic mouse with selective expression of human CXCR1 in the endothelium, activation of the IL-8-CXCR1 cascade by overexpression of IL-8 in tumor cells dramatically enhanced liver metastasis. Mechanistically, IL-8 selectively induced GARP-latent-TGF-ß in liver sinusoidal endothelial cells and subsequently provoked preferential regulatory T cell polarization to suppress antitumor immunity. Collectively, these findings reveal a hepatitis B-associated IL-8-CXCR1 signaling axis that mediates vascular invasion and local microenvironmental immune escape of HCC to induce intrahepatic metastasis, which may serve as potential therapeutic targets for HBV-associated HCC.

13.
Jpn J Ophthalmol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33656708

RESUMO

PURPOSE: To compare the differences between cycloplegic and noncycloplegic refraction as well as associated factors in grade one students of primary schools, and explore the effectiveness of noncycloplegic refraction for refractive error screening. STUDY DESIGN: Cross-sectional study. METHODS: A school-based study of 1856 students was conducted in Lhasa, Tibetan Plateau, China. Cycloplegia was achieved with two drops of 1% cyclopentolate and 1 drop of Mydrin P at a 5-min interval. Autorefraction was performed under both cycloplegic and noncycloplegic conditions. Bland-Altman analysis, receiver operating characteristic curve analysis, univariate and multiple linear regression models were used for analysis. RESULTS: Of the 1856 children enrolled, 1830 (98.60%) completed all procedures. The average age was 6.83 ± 0.46 years. 965 (52.73%) children were boys and 1737 (94.92%) were Tibetan. Overall, there was a significant difference between cycloplegic and noncycloplegic SE of 0.90 ± 0.76D (P < 0.001). However, the intra-class coefficient correlation (ICC) for cylinder between these two methods was high (ICC = 0.941, 95% CI, 0.935-0.946). Larger differences between cycloplegic and noncycloplegic SE were associated with hyperopic RE and higher cylindrical value (P < 0.001). The prevalence of myopia, emmetropia and hyperopia with and without cycloplegia was (3.93% vs 14.59%), (9.95% vs 45.8%) and (86.21% vs 39.56%), respectively. Myopia, emmetropia and hyperopia based on noncycloplegic refraction was defined as SE ≤ - 0.625D, - 0.625 < SE ≤ 0D, and SE > 0D, respectively. CONCLUSIONS: Lack of cycloplegia leads to underestimation of hyperopia, with overestimation of myopia and emmetropia. Larger hyperopic refraction exhibited greater difference between cycloplegic and noncycloplegic refraction.

14.
J Hazard Mater ; 414: 125450, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33676256

RESUMO

Triclosan (TCS) and methyl-triclosan (MTCS), an environmental transformation product of biocide of TCS, have been detected in water, sediment, fish, and invertebrates. In this study, the key pathway perturbation in zebrafish (Danio rerio) embryos exposed to TCS (300 µg/L) and TCS/MTCS mixture (300 µg/L TCS + 30 µg/L MTCS) was assessed by integrating the metabolomic and transcriptomic dysregulation. The differential expressed genes (DEGs) were obtained from the subtracted cDNA libraries by using the suppression subtractive hybridization and next-generation sequencing approach. The dysregulation of twenty-eight GO terms and four KEGG pathways, including oxidative phosphorylation and cardiac muscle contraction, were shown in the TCS treatment group, indicating that TCS could disrupt the mitochondrial inner membrane function by downshifting the electrochemical gradient. Meanwhile, the addition of MTCS in the exposure would cause fourteen additional significant KEGG pathway changes, demonstrating the different effects between two exposure. A pathway-based analysis using the identified DEGs and the altered metabolites in zebrafish embryos treated with TCS and TCS/MTCS mixture, collectively, has been applied. This study demonstrated that the integration of SSH-NGS and metabolomics could reveal toxic effects and potential diseases associated with the exposures of TCS and MTCS in aquatic environments.

15.
Med Sci Monit ; 27: e930865, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739959

RESUMO

BACKGROUND Obesity can influence thyroid function through multiple routes, even in people who are euthyroid. The correlation between weight and thyroid function is a matter of debate. The present study investigated the relationship between body weight and thyroid function in euthyroid Chinese adults. MATERIAL AND METHODS A total of 1564 participants with serum thyrotropin (TSH) and thyroid hormone levels within the reference range were included. All of them were tested for thyroid function parameters and categorized, based on body mass index (BMI), into 3 groups: normal weight, overweight, and obese. The effects of BMI on thyroid function were examined using linear (continuous values) and logistic (dichotomous levels according to medians or means) regression and controlling for age and sex. RESULTS There were significant differences in free triiodothyronine (FT3) levels and FT3/free thyroxine (FT4) ratios among participants who were normal weight, overweight, and obese (both P<0.001). Multivariable regression analysis (P<0.001) showed that BMI was positively associated with FT3 levels and FT3/FT4 ratios. Compared with the normal weight group, the patients who were overweight or obese had significantly higher FT3 levels and FT3/FT4 ratios that were higher than average, according to logistic regression analyses. CONCLUSIONS We found that Chinese adults who are obese may have higher FT3 levels and FT3/FT4 ratios than those who are of normal weight, even if their thyroid function values are within the normal range.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33649114

RESUMO

Intravenous administration of the last-line polymyxins results in poor drug exposure in the lungs and potential nephrotoxicity; while inhalation therapy offers better pharmacokinetics/pharmacodynamics for pulmonary infections by delivering the antibiotic to the infection site directly. However, polymyxin inhalation therapy has not been optimized and adverse effects can occur. This study aimed to quantitatively determine the intracellular accumulation and distribution of polymyxins in single human alveolar epithelial A549 cells. Cells were treated with an iodine-labeled polymyxin probe FADDI-096 (5.0 and 10.0 µM) for 1, 4, and 24 h. Concentrations of FADDI-096 in single A549 cells were determined by synchrotron-based X-ray fluorescence microscopy. Concentration- and time-dependent accumulation of FADDI-096 within A549 cells was observed. The intracellular concentrations (mean ± SEM, n ≥ 189) of FADDI-096 were 1.58 ± 0.11, 2.25 ± 0.10, and 2.46 ± 0.07 mM following 1, 4 and 24 h of treatment at 10 µM, respectively. The corresponding intracellular concentrations following the treatment at 5 µM were 0.05 ± 0.01, 0.24 ± 0.04, and 0.25 ± 0.02 mM (n ≥ 189). FADDI-096 was mainly localized throughout the cytoplasm and nuclear region over 24 h. The intracellular zinc concentration increased in a concentration- and time-dependent manner. This is the first study to quantitatively map the accumulation of polymyxins in human alveolar epithelial cells and provides crucial insights for deciphering the mechanisms of their pulmonary toxicity. Importantly, our results may shed light on the optimization of inhaled polymyxins in patients and the development of new-generation safer polymyxins.

17.
Chin Med J (Engl) ; 134(7): 792-799, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661141

RESUMO

BACKGROUND: Norepinephrine infusion decreases hypotension after spinal anesthesia during cesarean section. This study aimed to compare the efficacy of norepinephrine infusion and ephedrine bolus against post-spinal hypotension in parturients. METHODS: In this double-blinded, randomized controlled clinical trial, parturients scheduled for elective cesarean section were randomly allocated to receive norepinephrine infusion (0.05 µg·kg-1·min-1) just before spinal anesthesia continuing for 30 min or ephedrine bolus (0.15 mg/kg) just before spinal anesthesia. A rescue bolus (5 µg norepinephrine for the norepinephrine group, and 5 mg ephedrine for the ephedrine group) was administered whenever hypotension occurred. Our primary outcome was the incidence of hypotension within 30 min of spinal anesthesia administration. Secondary outcomes included maternal and neonatal outcomes 30 min after spinal block, and neonatal cerebral oxygenation 10 min after birth. RESULTS: In total, 190 patients were enrolled; of these patients, 177 were included in the final analysis. Fewer patients suffered hypotension in the norepinephrine group than in the ephedrine group (29.5% vs. 44.9%, odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.28-0.95, P = 0.034). Moreover, the tachycardia frequency was lower in the norepinephrine group than in the ephedrine group (OR: 0.22, 95% CI: 0.11-0.44, P < 0.001), and patients suffered less nausea and vomiting (OR: 0.28, 95% CI: 0.11-0.70, P = 0.004). There was no difference in Apgar scores and umbilical arterial blood gas analysis between the two groups. However, neonatal cerebral regional saturations were significantly higher after birth in the norepinephrine group than in the ephedrine group (mean difference: 2.0%, 95% CI: 0.55%-3.45%, P = 0.008). CONCLUSION: In patients undergoing elective cesarean section with spinal anesthesia, norepinephrine infusion compared to ephedrine bolus resulted in less hypotension and tachycardia, and exhibited potential neonatal benefits. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02542748; https://clinicaltrials.gov/ct2/show/record/NCT02542748.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33539033

RESUMO

OBJECTIVE: To evaluate the effectiveness of laparoscopic tubal anastomosis for tubal occlusions associated with infertility in patients with previous laparoscopic salpingostomy for ectopic pregnancy. METHODS: This study is a retrospective analysis of the pregnancy outcomes of 173 infertile patients who underwent hysteroscopy and laparoscopic tubal anastomosis treatment between January 2013 and August 2018 in the Department of Reproductive Endocrinology in West China Second University Hospital of Sichuan University. All patients had a history of laparoscopic salpingostomy for tubal pregnancy. The primary outcomes were intrauterine pregnancy, ectopic pregnancy, and delivery rates. We further studied the associated factors that could influence the change in pregnancy status. RESULTS: The 24-month cumulative clinical pregnancy rate of all patients was 107/173 (61.8%). The distribution of outcomes for the entire group of pregnancies was as follows: intrauterine pregnancy rate, 76/173 (43.9%); ectopic pregnancy rate, 31/173 (17.9%); delivery rate, 68/173 (39.3%); and miscarriage rate, 8/173 (4.6%). Age, type of anastomosis, hydrosalpinx, and endometrial polyps were significant prognostic factors in the multivariate model. CONCLUSION: Laparoscopic tubal anastomosis is an effective treatment for tubal-associated infertility due to previous laparoscopic salpingostomy for ectopic pregnancy, especially for women under 35 years of age.

19.
Endocr Pract ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33637446

RESUMO

OBJECTIVE: Prolactin (PRL) is a polypeptide hormone named for its crucial role in lactation. Recently, PRL has been recognized as a metabolic hormone that regulates energy metabolism. The current study aimed to investigate the relationship between circulating PRL and metabolic alterations in overweight/obese patients and the effect of weight loss through bariatric surgery on circulating PRL. METHODS: A total of 448 overweight/obese patients aged between 18 and 40 years and 120 age- and sex-matched healthy controls with normal weight were enrolled. Among all participants, 156 obese patients underwent bariatric surgery. RESULTS: Circulating PRL levels were significantly increased in the overweight (15.27 ± 9.58 µg/L) and obese (17.75 ± 9.15 µg/L) groups compared with the normal weight (13.57 ± 9.03 µg/L) group. Multiple regression analyses demonstrated that the adipose tissue insulin resistance (adipo-IR) level was an independent predictor for PRL (ß = -0.451, P < .01). Despite comparable anthropometric parameters, the overweight/obese patients with a higher PRL tertile had decreased levels of triglycerides, nonesterified fatty acids, homeostasis model assessment of insulin resistance, and adipo-IR compared with the patients in the moderate and lower PRL tertiles. Serum PRL levels were significantly decreased following the alleviation of metabolic parameters after bariatric surgery (from 17.12 ± 8.27 to 13.00 ± 5.78 µg/L, P < .05), and the decrease in PRL levels was significantly greater in the lower adipo-IR group than in the higher adipo-IR group (P < .01). CONCLUSION: An increased serum PRL level might be an adaptive response for protecting against metabolic disorders in obesity.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33604805

RESUMO

PURPOSE: We aimed to identify pathogenic variants in two infertile sisters in a family with a thin zona pellucida (ZP) phenotype. METHODS: Whole-exome sequencing was performed in the two affected sisters, and Sanger sequencing was used to confirm the identified variants. The effects of the identified variant were further investigated in mouse oocytes and Chinese hamster ovary (CHO) cells. RESULTS: We identified a novel homozygous frameshift variant in ZP2 (c.1235_1236del, p.Q412Rfs*17) in the two affected individuals. Immunoblotting demonstrated that the variant produced a truncated ZP2 protein that was expressed at low levels in CHO cells. Immunofluorescence in mouse oocytes confirmed the decreased protein level of mutant ZP2, although the subcellular localization was not affected. In addition, immunoprecipitation showed that the pathogenic variant reduced the interaction between ZP2 and ZP3. CONCLUSION: This study identified a novel pathogenic variant in ZP2 that produces a truncated ZP2 protein. The variant might disrupt the assembly of ZP2-ZP3 dimers, thus resulting in a thin ZP and female infertility.

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