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1.
Sex Transm Dis ; 2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34618416

RESUMEN

Background: In men with nongonococcal urethritis (NGU), clinicians and patients rely on clinical cure to guide the need for additional testing/treatment and when to resume sex, respectively; however, discordant clinical and microbiological cure outcomes do occur. How accurately clinical cure reflects microbiological cure in specific sexually transmitted infections (STI) is unclear. Methods: Men with NGU were tested for Neisseria gonorrhoeae, Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis, urethrotropic Neisseria meningitidis ST11 clade strains, and Ureaplasma urealyticum (UU). Men received azithromycin 1 g and returned for a 1-month test-of-cure visit. In MG infections, we evaluated for the presence of macrolide resistance-mediating mutations (MRM) and investigated alternate hypotheses for microbiological treatment failure using in situ shotgun metagenomic sequencing, phylogenetic analysis, multiple locus typing analyses, and quantitative PCR. Results: Of 280 men with NGU, 121 were included in this analysis. In the monoinfection group, 52 had CT, 16 had MG, 7 had UU, 10 had mixed infection, and 36 men had idiopathic NGU. Clinical cure rates were 85% for CT, 100% for UU, 50% for MG, and 67% for idiopathic NGU. Clinical cure accurately predicted microbiological cure for all STI, except MG. Discordant results were significantly associated with MG-NGU and predominantly reflected microbiological failure in men with clinical cure. MG MRM, but not MG load or strain, were strongly associated with microbiological failure. Conclusions: In azithromycin-treated NGU, clinical cure predicts microbiological cure for all STI, except MG. NGU management should include MG testing and confirmation of microbiological cure in azithromycin-treated MG-NGU when MRM testing is unavailable.

2.
J Control Release ; 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34655677

RESUMEN

The combination of nitric oxide (NO) and siRNA is highly desirable for cancer therapy. Here, the furoxans-grafted PEI polymer (FDP) with caspase-3 responsive cleavable DEVD linker was synthesized, and used to bind siRNAs via electrostatic interaction and self-assembled into FDP/siRNA nanoplexes by hydrophobic force. After cellular uptake and lysosomal escape, the FDP/siRNA nanoplexes could achieve GSH-triggered NO release, and then increase the activity of caspase-3. The activated caspase-3 could specifically cleave the DEVD peptide sequence and enhance cell apoptosis. With the cleavage of DEVD peptide sequence, the disassembly of FDP/siRNA nanoplexes was further promoted, thereby resulting in increased siRNAs of ~40% were released at 48 h compared with the caspase-3 non-responsive FDnP/siRNA nanoplexes. By this way, cell apoptosis promotion and cell proliferation inhibition was achieved by siRNA-based downregulation of EGFR protein and the upregulated activity of caspase-3, followed by the enhanced cascade release of NO from FDP/siRNA nanoplexes. Furthermore, in vivo results demonstrated the improved anti-cancer efficiency of FDP/siEGFR nanoplexes without any detectable side effects. Therefore, it is believed that the caspase-3 responsive cleavable furoxans-grafted PEI polymers could provide a potential and efficient enhancement for cancer therapeutic efficiency by the co-delivery of nitric oxide and siRNA.

3.
Artículo en Inglés | MEDLINE | ID: mdl-34595703

RESUMEN

An accurate NOx concentration prediction model plays an important role in low NOx emission control in power stations. Predicting NOx in advance is of great significance in satisfying stringent environmental policies. This study aims to accurately predict the NOx emission concentration at the outlet of boilers on different operating conditions to support the DeNOx procedure. Through mutual information analysis, suitable features are selected to build models. Long short-term memory (LSTM) models are utilized to predict NOx concentration at the boiler's outlet from selected input features and exhibit power in fitting multivariable coupling, nonlinear, and large time-delay systems. Moreover, a composite LSTM model composed of models on different operating conditions, like steady-state and transient-state condition, is prosed. Results of one whole day of typical operating data show that the accuracy of the NOx concentration and fluctuation trend prediction based on this composite model is superior to that using a single LSTM model and other non-time-sequence models. The root mean square error (RMSE) and R2 of the composite LSTM model are 3.53 mg/m3 and 0.89, respectively, which are better than those of a single LSTM (i.e., 5.50 mg/m3 and 0.78, respectively).

4.
J Am Chem Soc ; 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34641681

RESUMEN

Although a large number of novel supramolecular topologies featuring half-sandwich [Cp*Rh] units have been reported, investigations into the properties of these architectures are astoundingly rare. In addition, the bidentate ligands employed to prepare these species have remained relatively homogeneous (i.e., symmetrical bis(pyri-4-dyl) ligands). To address these paucities in the field, the novel unsymmetrical ligand L2 and the rarely reported pyri-3-dyl ligand L3, all bearing aromatic phenazine groups (an N-heterocyclic analog of anthracene), were synthesized in addition to the common symmetrical pyri-4-dyl L1. [3]Catenane, [2]catenane, and Borromean rings assemblies were constructed successfully by the self-assembly of L1 with different building blocks. Afterward, ligand L2 was applied to prepare two novel molecular-tweezer-like compounds. Lastly, a twisted [2]catenane (relative to the [2]catenane constructed using L1) and a sandwiched metallarectangle were obtained using L3. π-π stacking interactions were observed to play a significant role in stabilizing these topologies, which also promoted nonradiative migration and triggered photothermal conversion in both the solution and the solid state. In the solution state, a clear rule of thumb was derived whereby the NIR photothermal conversion efficiency increased as the π-π stacking increased, and a very high photothermal conversion efficiency (35.5-62.4%) was observed. In addition, this family of half-sandwich-based assemblies also exhibited good photothermal conversion properties in the crystalline and noncrystal powder states. This research provides a novel method to synthesize excellent NIR photothermal conversion materials featuring half-sandwich [Cp*Rh] units and points to potential applications in the near future.

5.
Int Ophthalmol ; 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34642840

RESUMEN

PURPOSE: To analyze functions of corneal biomechanical properties (CBP)-related variants as corneal resistance factor (CRF) and corneal hysteresis (CH). METHODS: Related single nucleotide polymorphisms (SNPs) and genes were identified from NHGRI-EBI GWAS catalog, GWASdb v2 and possible data in published studies. HaploReg v4.1 was used to find linkage SNPs. Functional annotations were performed by GWAVA, CADD and RegulomeDB. GTEx Portal database was used to find out expression quantitative trait locus (eQTL) association. Enrichr was used to annotate the function of GWAS gene and the associated signal pathway. STING (v11.0) database was utilized for protein interaction and network construction. RESULTS: The integration of 302 CH-associated and 420 CRF-associated lead SNPs has produced 531 CBP-associated lead SNPs. A total of 5,324 proxy variants identified using the HaploReg v4.1 and lead SNPs were functionally annotated. Based on the threshold (CADD ≥ 10, GWAVA ≥ 0.4 and RegulomeDB < rank 3), 23 prioritized putative regulatory SNPs were identified. Eight prioritized eQTL variants (rs75203695, rs34861673, rs846766, rs11024102, rs1377416, rs3829492, rs9934438 and rs197912) were found with strong potential of CBP regulation. It was indicated that CBP-associated genes were significantly enriched in extracellular matrix receptor interaction pathway, closely related to the phenotype of corneal dystrophy and keratoconus. COL1A1, SMAD3, BMP4 and RUNX2 occupied the core position in the co-expression network. CONCLUSIONS: Data integrative analysis can evaluate CBP variations and explore collagen and extracellular matrix pathways in CBP regulation, which is a promising tool to investigate biological process of corneal diseases.

6.
Food Funct ; 12(20): 9739-9749, 2021 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-34664591

RESUMEN

Sandalwood seed oil (SSO), rich in ximenynic acid, is extracted from the seed kernels of Santalum spicatum. The current work aimed to clarify the potential mechanisms of SSO in preventing insulin resistance (IR) by investigating the intestinal microbiota and its metabolites. Fifty male Sprague-Dawley rats were randomly divided into a standard chow group (N), and four high-fat/high-sucrose (HFHS) diet-fed groups plus 7% of SSO, fish oil (FO), linseed oil (LO) or sunflower oil (SO), respectively. After 12 weeks, the feces were collected and subsequently the rats were sacrificed for collecting blood and tissues. The results indicated that the SSO, FO and LO groups had a lower ratio of Firmicutes to Bacteroidetes (F/B) and lower levels of Actinobacteria phylum in their feces compared to the SO group. HOMA-IR was positively correlated with F/B (r = 0.63) and Actinobacteria (r = 0.64). At the genus level, beneficial bacteria, including Oscillospira, Clostridium, Turicibacter, Ruminococcus and Coprococcus, were more abundant, while destructive bacteria, such as Collinsella, were less abundant in the SSO group than in the SO group. The concentrations of fecal short-chain fatty acids (SCFAs) were higher, and the serum LPS and trimethylamine N-oxide (TMAO) were lower in the SSO, FO and LO groups than the SO group. In addition, SCFAs were negatively (r: -0.45 to -0.82), and LPS (r: 0.12 to 0.42) and TMAO (r: 0.32 to 0.49) were positively correlated with HOMA-IR and serum IL-1ß, IL-6 and TNF-α. In summary, the prevention effect of SSO on HFHS induced IR was associated with altered intestinal microbiota composition and the production of microbial metabolites.

7.
Opt Express ; 29(15): 23939-23952, 2021 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-34614648

RESUMEN

The ultrastrongly coupling (USC) system has very important research significance in quantum simulation and quantum computing. In this paper, the ultranarrow spectrum of a circuit QED system with two qubits ultrastrongly coupled to a single-mode cavity is studied. In the regime of USC, the JC model breaks down and the counter-rotating terms in the quantum Rabi Hamiltonian leads to the level anti-crossing in the energy spectrum. Choosing a single-photon driving field at the point of avoided-level crossing, we can get an equivalent four-level dressed state model, in which the dissipation of the two intermediate states is only related to the qubits decay. Due to the electron shelving of these two metastable states, a narrow peak appears in the cavity emission spectrum. Furthermore, we find that the physical origin for the spectral narrowing is the vacuum-induced quantum interference between two transition pathways. And this interference effect couples the slowly decaying incoherent components of the density matrix into the equations of the sidebands. This result provides a possibility for the study of quantum interference effect in the USC system.

8.
J Appl Microbiol ; 2021 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-34608718

RESUMEN

AIM: The metabolic markers and differentially expressed genes (DEGs) related to fructo-oligosaccharide (FOS) were screened, and the response of FOS to the ileum metabolic pathway of Taiping chickens was analysed. METHODS AND RESULTS: Prebiotic are widely used in agricultural breeding for care and maintenance of animal health, especially FOS. Metabonomics evaluation of ileum of Taiping chicken ultra-performance liquid chromatography-quadruple time of-flight high-sensitivity mass spectrometry showed that 93 differentially altered metabolites were identified and divided into eight categories, of which organic acids and derivatives was the most important one. Transcriptomic analysis showed that DEGs were mainly enriched in drug metabolism-cytochrome p450, metabolism of xenobiotics by cytochrome p450, retinol metabolism and fat digestion and absorption. Integrated analysis of metabolite profiles and gene expression revealed that the significantly up-regulated GSTT1 was significantly correlated with most of the different lipid metabolites, suggesting that GSTT1 may play an important role in FOS regulation of lipid metabolism. CONCLUSIONS: The results of this study suggest that supplementation of FOS can have a positive effect on gut metabolites, which may contribute to the overall health with indigenous chickens. SIGNIFICANCE AND IMPACT OF THE STUDY: Insight into the responses of intestinal prebiotics of Taiping chicken is helpful to understand the role of prebiotics in maintaining intestinal microflora balance and improving immune response and productivity of poultry from the molecular and metabolic levels.

9.
Sleep Med ; 87: 127-137, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34597954

RESUMEN

BACKGROUND: Obstructive sleep apnea (OSA) is one of the common sleep-related breathing disorders in children. However, polysomnography (PSG) is an expensive and labor-intensive diagnostic modality that may not always be feasible, especially in low-income countries or in non-tertiary hospitals. Portable monitors (PMs), a new approach for OSA diagnosis, have become more widely used with lower intolerance and cost in recent years. We aimed to analyze the diagnostic performance of Level IV PMs compared with PSG for the diagnosis of pediatric OSA. METHODS: PubMed and Embase databases were searched for studies published in English up to December 31, 2020 evaluating the diagnostic accuracy of Level IV PMs against the apnea-hypopnea index (AHI) measured using overnight in-laboratory polysomnography (PSG) in children and adolescents. A random-effects bivariate model was used to estimate the summary sensitivity and specificity of oximetry-based statistical classifiers. A qualitative evaluation of studies was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) rating. RESULTS: In total, 20 studies involving 7062 participants were included in this systematic review. Among these articles, seven studies (oximetry based on new mathematical classifiers) involving 5098 individuals satisfied the criteria for quantitative synthesis. Compared with AHI evaluation measured by PSG, different PM systems achieved diagnostic accuracy with variable degrees of success. A meta-analysis showed a pooled sensitivity of 74% (95% confidence interval [CI]: 66-80%) and pooled specificity of 90% (95% CI: 85-94%). The area under the summary receiver operating characteristic (SROC) curve was 0.89 (95% CI: 0.86-0.92). CONCLUSION: This study showed the potential of Level IV PMs for screening pediatric OSA patients. Oximetry based on new mathematical classifiers may provide a simple and effective alternative to PSG in the diagnosis of pediatric OSA especially in the context of appropriate clinical evaluation.

11.
J Oncol ; 2021: 4279039, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34659409

RESUMEN

Noncoding RNAs have been shown with powerful ability in post-transcriptional regulation, enabling intertwined RNA crosstalk and global molecular interaction in a large amount of dysfunctional conditions including cancer. Competing endogenous RNAs (ceRNAs) are those competitively binding with shared microRNAs (miRNAs), freeing their counterparts from miRNA-induced degradation, thus actively influencing and connecting with each other. Constantly updated analytical approaches boost outstanding advancement achieved in this burgeoning hotspot in multilayered intracellular communication, providing new insights into pathogenesis and clinical treatment. Here, we summarize the mechanisms and correlated factors under this RNA interplay and deregulated transcription profile in neoplasm and tumor progression, underscoring the great significance of ceRNAs for diagnostic values, monitoring biomarkers, and prognosis evaluation in cancer.

12.
BMC Ophthalmol ; 21(1): 371, 2021 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-34666717

RESUMEN

BACKGROUND: Rhodopsin (RHO) is the most well-known genetic cause of autosomal dominant retinitis pigmentosa (adRP). This study aimed to investigate the genetic cause of a large Chinese adRP family and assess the pathogenicity of the detected RHO mutant. METHODS: Routine ocular examinations were conducted on all participants. Next-generation sequencing with targeted capture was performed to screen mutations in 179 genes associated with hereditary retinal diseases and 10 candidate genes. Variants detected by NGS were validated by Sanger sequencing and evaluated for pathogenicity. Fragments of mutant and wild-type RHO were cloned into the pEGFP-N1 vector and were transfected into different cell lines to observe the cellular localization of the Rhodopsin-GFP fusion protein and evaluate the expression of endoplasmic reticulum (ER) stress markers. RT-PCR analysis was used to detect transfected the splicing of X box-binding protein 1 (XBP1) mRNA, which is a critical factor affecting ER stress. RESULTS: Genetic analysis identified a heterozygous missense variant, RHO, c.284 T > C (p.L95P) in this adRP family. Another RHO variant (p.P53R) that we reported previously was also included in further functional assessment. Both misfolded mutant proteins accumulated in the ER in a manner similar to that noted for the classic mutant P23H. Spliced XBP1 was observed in cells transfected with mutants, indicating an increase in ER stress. CONCLUSIONS: Although the p.L95P variant is not a novel change, it was the first variant to be functionally evaluated and reported in Chinese RP patients. The results in our study provide significant evidence to classify the p.L95P mutation as a class II mutation.


Asunto(s)
Retinitis Pigmentosa , Rodopsina , Estrés del Retículo Endoplásmico/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Linaje , Retinitis Pigmentosa/genética , Rodopsina/genética
13.
Int J Ophthalmol ; 14(10): 1508-1517, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34667726

RESUMEN

AIM: To investigate the protective effect of human umbilical cord mesenchymal stem cells (hUCMSCs) modified by the LIF gene on the retinal function of diabetic model rats and preliminarily explore the possible mechanism. METHODS: A stably transfected cell line of hUCMSCs overexpressing leukemia inhibitory factor (LIF) was constructed. Overexpression was verified by fluorescent quantitative polymerase chain reaction (qPCR). Forty-eight adult Sprague-Dawley rats were randomly divided into a normal control group (group A), streptozotocin-induced diabetic control group (group B), diabetic rats at 3mo injected with empty vector-transfected hUCMSCs (group C) or injected with LIF-hUCMSCs (group D). Four weeks after the intravitreal injection, analyses in all groups included retinal function using flash electroretinogram (F-ERG), retinal blood vessel examination of retinal flat mounts perfused with fluorescein isothiocyanate-dextran (FITC-dextran), and retinal structure examination of sections using hematoxylin and eosin staining. Expression levels of adiponectin (APN), high-sensitivity C-reactive protein (hs-CRP), and neurotrophin-4 (NT-4) in each group was detected using immunohistochemistry, PCR, Western blotting, and ELISA, respectively. RESULTS: A stable transgenic cell line of LIF-hUCMSCs was constructed. F-ERG and FITC-dextran examinations revealed no abnormalities of retinal structure and function in group A, severe damage of the retinal blood vessels and function in group B, and improved retinal structure and function in group C and especially group D. qPCR, ELISA, and Western blot analyses revealed progressively higher APN and NT-4 expression levels in groups B, C, and D than in group A. hs-CRP expression was significantly higher in group B than in groups A, C, and D, and was significantly higher in group C than in group D (P<0.05). CONCLUSION: LIF-hUCMSCs protect the retina of diabetic rats by upregulating APN and NT-4 expression and downregulating hs-CRP expression in the retina.

14.
Aging (Albany NY) ; 13(19): 23119-23132, 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-34620733

RESUMEN

The anticancer effect of zinc oxide nanoparticles (ZnO NPs) largely relies on cellular responses such as alteration of gene expression. Although ZnO NPs have been reported to induce transcriptional changes, the potential of ZnO NPs to affect cellular translatome remains largely unknown. Using ribosome profiling, we demonstrated that the transcription of 78 genes and the translation of 1,448 genes are affected during one hour of ZnO NPs exposure in A549 human lung cancer cells. The mitogen-activated protein kinase (MAPK) pathway is up-regulated upon ZnO NP treatment. The upstream open reading frame (uORF) plays a pervasive role in the induction of up-regulated genes, including TLNRD1 and CCNB1IP1. Knockdown of TLNRD1 or CCNB1IP1 reduces ZnO NP-induced cytotoxicity. Together, our study characterizes the landscape of translational alteration under ZnO NPs treatment and provides potential targets to augment the anticancer effect of ZnO NPs.

15.
Nutr J ; 20(1): 80, 2021 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-34548082

RESUMEN

BACKGROUND: Whether mushroom consumption, which is a rich source of potent antioxidants ergothioneine and glutathione, vitamins, and minerals (e.g., selenium & copper), is associated with a lower mortality risk is not well understood. This study aimed to examine the association between mushroom consumption and risk of mortality in a prospective cohort study and a meta-analysis of prospective cohort studies. METHODS: We followed 30,378 participants from the continuous National Health and Nutrition Examination Survey (NHANES) extant data (2003-2014). Dietary mushroom intake was assessed using up to two 24-h recalls. Mortality was evaluated in all participants linked to the National Death Index mortality data through December 31, 2015. We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). We also conducted a meta-analysis, including results from our present study and 4 other cohort studies. RESULTS: During a mean (SD) of 6.7 (3.4) years of follow-up, a total of 2855 death cases were documented among NHANES participants. In our analysis of continuous NHANES, we found a non-significant association between mushroom consumption and all-cause mortality (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.67-1.06) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors, including total energy. The meta-analysis of prospective cohort studies, including 601,893 individuals, showed that mushroom consumption was associated with a lower risk of all-cause mortality (pooled risk ratio: 0.94; 95% CI: 0.91, 0.98). CONCLUSION: In a meta-analysis of prospective cohort studies, mushroom consumption was associated with a lower risk of all-cause mortality.


Asunto(s)
Agaricales , Enfermedades Cardiovasculares , Estudios de Cohortes , Dieta , Humanos , Mortalidad , Encuestas Nutricionales , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo
16.
mBio ; 12(4): e0065621, 2021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34465018

RESUMEN

Human gut microbes exhibit a spectrum of cooperative and antagonistic interactions with their host and also with other microbes. The major Bacteroides host-targeting virulence factor, Bacteroides fragilis toxin (BFT), is produced as an inactive protoxin by enterotoxigenic B. fragilis strains. BFT is processed by the conserved bacterial cysteine protease fragipain (Fpn), which is also encoded in B. fragilis strains that lack BFT. In this report, we identify a secreted antibacterial protein (fragipain-activated bacteriocin 1 [Fab1]) and its cognate immunity protein (resistance to fragipain-activated bacteriocin 1 [RFab1]) in enterotoxigenic and nontoxigenic strains of B. fragilis. Although BFT and Fab1 share no sequence identity, Fpn also activates the Fab1 protoxin, resulting in its secretion and antibacterial activity. These findings highlight commonalities between host- and bacterium-targeting toxins in intestinal bacteria and suggest that antibacterial antagonism may promote the conservation of pathways that activate host-targeting virulence factors. IMPORTANCE The human intestine harbors a highly complex microbial community; interpersonal variation in this community can impact pathogen susceptibility, metabolism, and other aspects of health. Here, we identified and characterized a commensal-targeting antibacterial protein encoded in the gut microbiome. Notably, a shared pathway activates this antibacterial toxin and a host-targeting toxin. These findings highlight unexpected commonalities between host- and bacterium-targeting toxins in intestinal bacteria.

17.
Aliment Pharmacol Ther ; 54(9): 1124-1133, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34563096

RESUMEN

INTRODUCTION: Thiopurine S-methyltransferase (TPTM) is a well known biomarker for thiopurine-induced leucopenia, which has limited value in Asia. Instead, NUDT15 C415T is a promising predictor in Asia. AIMS: To explore whether an optimised strategy based on NUDT15 C415T genotypes affects thiopurine-induced leucopenia, as well as efficacy in Chinese patients with Crohn's disease. METHODS: Patients with Crohn's disease and indications for thiopurines were included from two hospitals in China. They were randomly assigned to either the intervention or the control group. In the intervention group, those with genotype CC received a standard dose (control group), those with CT genotype received 50% of the standard dose, those with TT genotype received alternative drugs. The primary endpoint was thiopurine-induced leucopenia (<3.5 × 109 /L). Secondary outcomes were the incidence of other adverse events and the efficacy for maintaining steroid-free remission at week 36. RESULTS: The rate of thiopurine-induced leucopenia was lower in the intervention group (n = 52) than in the control group (n = 66) (23.7% vs 32.4%, P = 0.049, RR = 0.73, 95% CI 0.53-1.00). In CT subgroup, the incidence of leucopenia in the intervention group (n = 10) was significantly lower than in the control group (n = 28) (31.3% vs 65.1%, RR = 0.48, 95% CI 0.28-0.84). Neither other adverse events nor treatment efficacy was significantly different between the two groups during follow-up. CONCLUSIONS: Among Chinese patients with Crohn's disease, dose optimisation by NUDT15 C415T reduced the rate of thiopurine-induced leucopenia, without significant influence on efficacy. Using 50% dose reduction for heterozygotes, and alternative drugs for homozygotes, are practicable strategies. Clinical trial number: NCT02929706.

18.
Am J Surg ; 2021 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-34530984

RESUMEN

INTRODUCTION: Colorectal adenosquamous carcinoma (ASC) represents <0.1% of colorectal cancers. Due to its rarity, there is paucity of data regarding its prognosis and treatment compared to other colorectal cancers. The aim of the study was to evaluate presentation, treatment and prognosis of colorectal ASC in comparison to adenocarcinoma (AC) and squamous cell carcinoma (SCC). METHODS: Adult patients diagnosed with colorectal AC, SCC, and ASC between 2000 and 2017 were identified using Surveillance, Epidemiology, and End Results database. RESULTS: Among the 446,132 patients diagnosed with colorectal cancer, 0.06% had ASC and were more likely to present with higher T stage and distant metastases compared to AC and SCC (p < 0.001). Major surgery was the primary treatment for colonic ASC, while for rectal ASC, chemotherapy and/or radiation were mainly utilized. Localized and distant colonic ASC had an unadjusted 5-year cause-specific survival that was worse than AC, while rectal ASC had the worst survival across all stages. CONCLUSION: Colorectal ASC usually present with advanced stage and have overall worse prognosis. Standardization of treatment strategies may improve survival in colorectal ASC.

19.
Pharmacogenomics ; 22(14): 903-912, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34523354

RESUMEN

Aim: Sirolimus (SIR) is an immunosuppressant with limitations, including a narrow treatment window, multiple adverse reactions and large differences within and among individuals. Objective: The correlation between numerous SNPs and SIR in terms of trough concentration in the early stage after kidney transplantation was analyzed. Materials & methods: A retrospective cohort study involving 69 kidney transplantation recipients was designed. Blood samples were collected to extract total DNAs, and trough SIR concentrations were measured. Logistic regression was used to analyze the association between SNPs and SIR trough concentrations. Results: At 7 days, 1 month and 3 months, the mean SIR trough concentration of patients in the CYP3A5 rs4646453-CC group was significantly higher than that in the CYP3A5 rs4646453-AA and CYP3A5 rs4646453-CA groups (p < 0.001) and CYP3A5 rs15524-AA group was significantly higher than that in the CYP3A5 rs15524-AG and CYP3A5 rs15524-GG groups (p < 0.001). Conclusion: Our study indicated that both CYP3A5 rs4646453 and CYP3A5 rs15524 had a certain influence on SIR trough concentration at 7 days, 1 month and 3 months.

20.
Mater Horiz ; 8(10): 2834-2841, 2021 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-34486000

RESUMEN

Soft biological tissues and muscles composed of semiflexible networks exhibit rapid strain-hardening behaviors to protect them from accidental rupture. In contrast, synthetic soft elastomers, usually featuring flexible networks, lack such behaviors, leading to a notorious issue when applying them to a promising artificial muscle technology (dielectric elastomer, DE), that is electromechanical instability (EMI) induced premature breakdown. We report that a facile thermomechanical training method can adaptively reconstruct the network of a soft triblock copolymer elastomer to transform its flexible network strands into semiflexible ones without extra chemical modifications and additives so that the electro-actuation performance is significantly enhanced by avoiding EMI. The free-standing actuators of trained elastomers exhibit a large stable electro-actuation strain and a high theoretical energy density (133%, 307 kJ m-3 at 158.1 V µm-1), and the capacity of actuating at low-temperature environments (-15 °C).

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