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1.
J Am Chem Soc ; 146(32): 22829-22839, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39086019

RESUMEN

The molecular editing of ketones represents an appealing strategy due to its ability to maximize the structural diversity of ketone compounds in a straightforward manner. However, developing efficient methods for the arbitrary modification of ketonic molecules, particularly those integrated within complex skeletons, remains a significant challenge. Herein, we present a unique strategy for ketone recasting that involves radical acylation of pre-functionalized ketones facilitated by N-heterocyclic carbene and photo dual catalysis. This protocol features excellent substrate tolerance and can be applied to the convergent synthesis and late-stage functionalization of structurally complex bioactive ketones. Mechanistic investigations, including experimental studies and density functional theory (DFT) calculations, shed light on the reaction mechanism and elucidate the basis of the regioselectivity.

2.
Pharmacol Res ; 206: 107284, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38925462

RESUMEN

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE2 injection either to the paw or the cranial dura. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1 knockout mice) and by eFT508, a specific MNK inhibitor. Sensory neuron-specific knockout of EphB2 using Pirt-Cre demonstrated that ephrin-B2 actions require this receptor. In Ca2+-imaging experiments on cultured DRG neurons, ephrin-B2 treatment enhanced Ca2+ transients in response to PGE2 and these effects were absent in DRG neurons from MNK1-/- and EphB2-PirtCre mice. In experiments on human DRG neurons, ephrin-B2 increased eIF4E phosphorylation and enhanced Ca2+ responses to PGE2 treatment, both blocked by eFT508. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling, offering new insight into how ephrin-B signaling promotes pain.


Asunto(s)
Efrina-B2 , Factor 4E Eucariótico de Iniciación , Hiperalgesia , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor EphB2 , Transducción de Señal , Animales , Hiperalgesia/metabolismo , Humanos , Masculino , Receptor EphB2/metabolismo , Receptor EphB2/genética , Femenino , Efrina-B2/metabolismo , Efrina-B2/genética , Factor 4E Eucariótico de Iniciación/metabolismo , Factor 4E Eucariótico de Iniciación/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Ratones , Nocicepción/efectos de los fármacos , Células Cultivadas , Nociceptores/metabolismo
3.
Helicobacter ; 29(4): e13079, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38984661

RESUMEN

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.


Asunto(s)
Antibacterianos , Bismuto , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/terapia , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Trasplante de Microbiota Fecal/métodos , Masculino , Femenino , Persona de Mediana Edad , Helicobacter pylori/efectos de los fármacos , Adulto , Antibacterianos/uso terapéutico , Estudios Prospectivos , Bismuto/uso terapéutico , Quimioterapia Combinada , China , Amoxicilina/uso terapéutico , Claritromicina/uso terapéutico , Resultado del Tratamiento , Anciano , Heces/microbiología
4.
Analyst ; 149(7): 2097-2102, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38421038

RESUMEN

In this work, we developed a rapid and sensitive label-free ratiometric fluorescent (FL) probe for the detection of bleomycin (BLM). The probe consists of a DNA sequence (D6) and two fluorophore groups, 2-amino-5,6,7-trimethyl-1,8-naphthalene (ATMND) and SYBR Green I (SGI). The D6 sequence could be folded into a three-way junction structure containing a C-C mismatch position in the junction pocket. The unique "Y" structure not only could entrap ATMND in the mismatch pocket with high affinity, leading to FL quenching at 408 nm, but also embed SGI in the grooves of the double-stranded portion, resulting in FL enhancement at 530 nm. In the presence of BLM-Fe(II), the "Y" structure of D6 was destroyed due to the specific cleavage of the BLM recognition site, the 5'-GT-3' site in D6. This caused the release of ATMND and SGI and thus the ratiometric signal change of FL enhancement by ATMND and FL quenching by SGI. Under optimal conditions, the ratiometric probe exhibited a linear correlation between the intensity ratio of F408/F530 and the concentration of BLM in the range of 0.5-1000 nM, with a detection limit of 0.2 nM. In addition, the probe was applied to detect BLM in human serum samples with satisfactory results, indicating its good clinical application potential.


Asunto(s)
Benzotiazoles , Bleomicina , Diaminas , Colorantes Fluorescentes , Quinolinas , Humanos , Colorantes Fluorescentes/química , Límite de Detección , Espectrometría de Fluorescencia/métodos
5.
BMC Med Imaging ; 24(1): 88, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38615005

RESUMEN

PURPOSE: This study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T. METHODS: Twelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC). RESULTS: A total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p < 0.001). The CNR was also significantly greater at 5.0 T than at 3.0 T for grey matter/tumour lesions, white matter/tumour lesions, and grey matter/white matter (p < 0.001). Subjective evaluation revealed that the internal structure and outline of the tumour lesions were more clearly displayed with a half-dose at 5.0 T (Likert scale 8.1 ± 0.3 at 3.0 T, 8.9 ± 0.3 at 5.0 T, p < 0.001), and the effects of enhancement in the lesions were comparable to those with a full dose at 3.0 T (7.8 ± 0.3 at 3.0 T, 8.7 ± 0.4 at 5.0 T, p < 0.001). All subjective scores were good to excellent at both 5.0 T and 3.0 T. CONCLUSION: Both quantitative and subjective evaluation parameters suggested that half-dose enhanced scanning via 5.0 T MRI might be feasible for meeting clinical diagnostic requirements, as the image quality remains optimal. Enhanced scanning at 5.0 T with a half-dose of contrast agents might benefit patients with conditions that require less intravenous contrast agent, such as renal dysfunction.


Asunto(s)
Neoplasias Encefálicas , Medios de Contraste , Humanos , Estudios de Factibilidad , Neoplasias Encefálicas/diagnóstico por imagen , Sustancia Gris , Radiólogos
6.
Neurosurg Rev ; 47(1): 109, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38456944

RESUMEN

OBJECTIVE: To develop a clinical-radiomics nomogram based on clinical information and radiomics features to predict the prognosis of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia (TN). METHODS: The retrospective study involved clinical data from 149 TN patients undergoing PBC at Zhongnan Hospital, Wuhan University from January 2018 to January 2022. The free open-source software 3D Slicer was used to extract all radiomic features from the intraoperative X-ray balloon region. The relationship between clinical information and TN prognosis was analyzed by univariate logistic analysis and multivariate logistic analysis. Using R software, the optimal radiomics features were selected using the least absolute shrinkage and selection operator (Lasso) algorithm. A prediction model was constructed based on the clinical information and radiomic features, and a nomogram was visualized. The performance of the clinical radiomics nomogram in predicting the prognosis of PBC in TN treatment was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 149 patients were eventually included. The clinical factors influencing the prognosis of TN in univariate analysis were compression severity score and TN type. The lasso algorithm Max-Relevance and Min-Redundancy(mRMR) was used to select two predictors from 13 morphology-related radiomics features, including elongation and surface-volume ratio. A total of 4 predictors were used to construct a prediction model and nomogram. The AUC was 0.886(95% confidence interval (CI), 0.75 to 0.96), indicating that the model's good predictive ability. DCA demonstrated the nomogram's high clinical applicability. CONCLUSION: Clinical-radiomics nomogram constructed by combining clinical information and morphology-related radiomics features have good potential in predicting the prognosis of TN for PBC treatment. However, this needs to be further studied and validated in several independent external patient populations.


Asunto(s)
Nomogramas , Neuralgia del Trigémino , Humanos , Radiómica , Estudios Retrospectivos , Neuralgia del Trigémino/diagnóstico por imagen , Neuralgia del Trigémino/cirugía , Pronóstico
7.
Int J Bipolar Disord ; 12(1): 5, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388844

RESUMEN

BACKGROUND: Systemic inflammation-immune dysregulation and brain abnormalities are believed to contribute to the pathogenesis of bipolar disorder (BD). However, the connections between peripheral inflammation and the brain, especially the interactions between different BD subtypes and episodes, remain to be elucidated. Therefore, we conducted the present study to provide a comprehensive understanding of the complex association between peripheral inflammation and neuroimaging findings in patients with bipolar spectrum disorders. METHODS: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42023447044) and conducted according to the Population, Intervention, Comparison, Outcomes, and Study Design (PICOS) framework. Online literature databases (PubMed, Web of Science, Scopus, EMBASE, MEDLINE, PsycINFO, and the Cochrane Library) were searched for studies that simultaneously investigated both peripheral inflammation-related factors and magnetic resonance neurography of BD patients up to July 01, 2023. Then, we analysed the correlations between peripheral inflammation and neuroimaging, as well as the variation trends and the shared and specific patterns of these correlations according to different clinical dimensions. RESULTS: In total, 34 publications ultimately met the inclusion criteria for this systematic review, with 2993 subjects included. Among all patterns of interaction between peripheral inflammation and neuroimaging, the most common pattern was a positive relationship between elevated inflammation levels and decreased neuroimaging measurements. The brain regions most susceptible to inflammatory activation were the anterior cingulate cortex, amygdala, prefrontal cortex, striatum, hippocampus, orbitofrontal cortex, parahippocampal gyrus, postcentral gyrus, and posterior cingulate cortex. LIMITATIONS: The small sample size, insufficiently explicit categorization of BD subtypes and episodes, and heterogeneity of the research methods limited further implementation of quantitative data synthesis. CONCLUSIONS: Disturbed interactions between peripheral inflammation and the brain play a critical role in BD, and these interactions exhibit certain commonalities and differences across various clinical dimensions of BD. Our study further confirmed that the fronto-limbic-striatal system may be the central neural substrate in BD patients.

8.
Chem Commun (Camb) ; 60(28): 3854-3857, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38497353

RESUMEN

In contrast to the well-established enzymatic enantioselective decarboxylative protonation (EDP), the corresponding chemocatalytic reactions of acyclic malonic acid derivatives remain challenging. Herein, we developed a biomimetic EDP of α-alkyl-α-aryl malonate monoesters using a chiral 1,2-trans-diaminocyclohexane-based N-sulfonamide as an organocatalyst. The method demonstrates excellent chemical yields, good enantioselectivity, mild reaction conditions, and the generation of only CO2 as waste.

9.
Front Pediatr ; 12: 1349670, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650991

RESUMEN

Background: Numerous studies have examined the association between obesity and age at menarche (AAM), with most focusing on traditional obesity indicators such as body mass index. However, there are limited studies that explored the connection between body fat distribution and AAM, as well as a scarcity of Mendelian randomization (MR) studies. Methods: In this study, we conducted a two-sample MR study to evaluate the causal effects of eight body fat distribution indicators on AAM. Inverse variance weighted (IVW) method was used for primary analysis, while supplementary approaches such as MR-Egger and weighted median were also utilized. Considering that the eight exposures were highly correlated, we performed an MR Bayesian model averaging (MR-BMA) analysis to prioritize the effect of major exposure on AAM. A series of sensitivity analyses were also performed. Results: From a range of 82-105 single nucleotide polymorphisms (SNPs) were utilized as genetic instrumental variables for each of the exposure factors. After Bonferroni correction, we found that whole body fat mass (ß: -0.17; 95% CI: -0.24, -0.11), left leg fat percentage (ß: -0.14; 95% CI: -0.21, -0.07), left leg fat mass (ß: -0.20; 95% CI: -0.27, -0.12), left arm fat percentage (ß: -0.18; 95% CI: -0.26, -0.11) and left arm fat mass (ß: -0.18; 95%CI: -0.26, -0.10) were associated with decreased AAM using random effects IVW method. And the beta coefficients for all MR evaluation methods exhibited consistent trends. MR-BMA method validated that left arm fat percentage plays a dominant role in AAM. Conclusions: Our MR study suggested that body fat has broad impacts on AAM. Obtaining more information on body measurements would greatly enhance our comprehension of pubertal development.

10.
Dent Mater ; 40(4): 728-738, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38401993

RESUMEN

OBJECTIVES: Guided Tissue Regeneration (GTR) is a popular clinical procedure for periodontal tissue regeneration. However, its key component, the barrier membrane, is largely collagen-based and is still quite expensive, posing a financial burden to the patients as well as healthcare systems and negatively impacting the patient's decision-making. Thus, our aim is to prepare a novel biomimetic GTR membrane utilizing a natural biomaterial, soluble eggshell membrane protein (SEP), which is economical as it comes from an abundant industrial waste from food and poultry industries, unlike collagen. Additive polymer, poly (lactic-co-glycolic acid) (PLGA), and a bioceramic, nano-hydroxyapatite (HAp), were added to improve its mechanical and biological properties. METHODS: For this barrier membrane preparation, we initially screened the significant factors affecting its mechanical properties using Taguchi orthogonal array design and further optimized the significant factors using response surface methodology. Furthermore, this membrane was characterized using SEM, EDAX, and ATR-FTIR, and tested for proliferation activity of human periodontal ligament fibroblasts (HPLFs). RESULTS: Optimization using response surface methodology predicted that the maximal tensile strength of 3.1 MPa and modulus of 39.9 MPa could be obtained at membrane composition of 8.9 wt% PLGA, 7.2 wt% of SEP, and 2 wt% HAp. Optimized PLGA/SEP/HAp membrane specimens that were electrospun on a static collector showed higher proliferation activity of HPLFs compared to tissue culture polystyrene and a commercial collagen membrane. SIGNIFICANCE: From the results observed, we can conclude that SEP-based nanofibrous GTR membrane could be a promising, environment-friendly, and cost-effective alternative for commercial collagen-based GTR membrane products.


Asunto(s)
Materiales Biocompatibles , Regeneración Tisular Dirigida , Animales , Humanos , Materiales Biocompatibles/farmacología , Cáscara de Huevo , Ensayo de Materiales , Colágeno , Durapatita
11.
Arch Dermatol Res ; 316(5): 144, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695894

RESUMEN

Hand infection is a rare complication in patients with diabetes. Its clinical outcomes depend on the severity of hand infection caused by bacteria, but the difference in bacterial species in the regional disparity is unknown. The purpose of this study was to explore the influence of tropical and nontropical regions on bacterial species and clinical outcomes for diabetic hand. A systematic literature review was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Moreover, the bacterial species and clinical outcomes were analyzed with respect to multicenter wound care in China (nontropical regions). Both mixed bacteria (31.2% vs. 16.6%, p = 0.014) and fungi (7.5% vs. 0.8%, p = 0.017) in the nontropical region were significantly more prevalent than those in the tropical region. Staphylococcus and Streptococcus spp. were dominant in gram-positive bacteria, and Klebsiella, Escherichia coli, Proteus and Pseudomonas in gram-negative bacteria occupied the next majority in the two regions. The rate of surgical treatment in the patients was 31.2% in the nontropical region, which was significantly higher than the 11.4% in the tropical region (p = 0.001). Although the overall mortality was not significantly different, there was a tendency to be increased in tropical regions (6.3%) compared with nontropical regions (0.9%). However, amputation (32.9% vs. 31.3%, p = 0.762) and disability (6.3% vs. 12.2%, p = 0.138) were not significantly different between the two regions. Similar numbers of cases were reported, and the most common bacteria were similar in tropical and nontropical regions in patients with diabetic hand. There were more species of bacteria in the nontropical region, and their distribution was basically similar, except for fungi, which had differences between the two regions. The present study also showed that surgical treatment and mortality were inversely correlated because delays in debridement and surgery can deteriorate deep infections, eventually leading to amputation and even death.


Asunto(s)
Bacterias , Infecciones Bacterianas , Mano , Humanos , Amputación Quirúrgica/estadística & datos numéricos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/terapia , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/mortalidad , China/epidemiología , Complicaciones de la Diabetes/microbiología , Complicaciones de la Diabetes/epidemiología , Mano/microbiología , Resultado del Tratamiento , Clima Tropical
12.
Dalton Trans ; 53(33): 13925-13932, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39099252

RESUMEN

The design of novel energetic compounds constitutes a pivotal research direction within the field of energetic materials. However, exploring the intricate relationship between their molecular structure and properties, in order to uncover their potential applications, remains a challenging endeavor. Therefore, employing multi-molecule assembly techniques to modulate the structure and performance of energetic materials holds immense significance. This approach enables the creation of a new generation of energetic materials, fueling research and development efforts in this field. In this study, a series of coordination compounds are synthesized by utilizing tetranitroethide (TNE) as an anion, which possesses a high nitrogen and oxygen content. The synthesis involves the synergistic modification between metal ions and small molecule ligands. Characterization of the obtained compounds is carried out using various techniques, including single crystal X-ray diffraction, IR spectroscopy, elemental analysis, and simultaneous TG-DSC analysis. Additionally, the energy of formation for these compounds is calculated using bomb calorimetry, based on the heat of combustion. The detonation performances of the compounds are determined through calculations using the EXPLO 5 software, and their sensitivities to external stimuli are evaluated.

13.
Gene ; 890: 147824, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-37741592

RESUMEN

BACKGROUND: Sickle cell disease (SCD) is a common inherited blood disorder among African Americans (AA), with premature mortality which has been associated with prolongation of the heart rate-corrected QT interval (QTc), a known risk factor for sudden cardiac death. Although numerous genetic variants have been identified as contributors to QT interval prolongation in the general population, their impact on SCD patients remains unclear. This study used an unweighted polygenic risk score (PRS) to validate the previously identified associations between SNPs and QTc interval in SCD patients, and to explore possible interactions with other factors that prolong QTc interval in AA individuals with SCD. METHODS: In SCD patients, candidate genetic variants associated with the QTc interval were genotyped. To identify any risk SNPs that may be correlated with QTc interval prolongation, linear regression was employed, and an unweighted PRS was subsequently constructed. The effect of PRS on the QTc interval was evaluated using linear regression, while stratification analysis was used to assess the influence of serum alanine transaminase (ALT), a biomarker for liver disease, on the PRS effect. We also evaluated the PRS with the two subcomponents of QTc, the QRS and JTc intervals. RESULTS: Out of 26 candidate SNPs, five risk SNPs were identified for QTc duration under the recessive model. For every unit increase in PRS, the QTc interval prolonged by 4.0 ms (95% CI: [2.0, 6.1]; p-value: <0.001) in the additive model and 9.4 ms in the recessive model (95% CI: [4.6, 14.1]; p-value: <0.001). Serum ALT showed a modification effect on PRS-QTc prolongation under the recessive model. In the normal ALT group, each PRS unit increased QTc interval by 11.7 ms (95% CI: [6.3, 17.1]; p-value: 2.60E-5), whereas this effect was not observed in the elevated ALT group (0.9 ms; 95% CI: [-7.0, 8.8]; p-value: 0.823). CONCLUSION: Several candidate genetic variants are associated with QTc interval prolongation in SCD patients, and serum ALT acts as a modifying factor. The association of a CPS1 gene variant in both QTc and JTc duration adds to NOS1AP as evidence of involvement of the urea cycle and nitric oxide metabolism in cardiac repolarization in SCD. Larger replication studies are needed to confirm these findings and elucidate the underlying mechanisms.


Asunto(s)
Anemia de Células Falciformes , Síndrome de QT Prolongado , Humanos , Síndrome de QT Prolongado/genética , Electrocardiografía , Muerte Súbita Cardíaca/etiología , Factores de Riesgo , Anemia de Células Falciformes/genética , Proteínas Adaptadoras Transductoras de Señales/genética
14.
Alzheimers Res Ther ; 16(1): 14, 2024 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-38245754

RESUMEN

BACKGROUND: Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. METHODS: We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. RESULTS: The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. CONCLUSIONS: VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.


Asunto(s)
Estudio de Asociación del Genoma Completo , MicroARNs , Humanos , Anciano , Estudio de Asociación del Genoma Completo/métodos , Multiómica , Memoria , Cognición , Polimorfismo de Nucleótido Simple/genética
15.
Artículo en Zh | WPRIM | ID: wpr-981441

RESUMEN

This study aimed to investigate the development status of traditional Chinese medicine(TCM) intervention in psoriasis in recent ten years, analyze the research hotspots, and summarize the development trends to provide reference materials for scholars in this field. Taking the available literature related to the field of TCM intervention in psoriasis as the research object, the trends, contents, and source publications were statistically analyzed based on bibliometrics. The research cooperation and co-occurrence of keywords in this field were studied by the knowledge map analysis method based on CiteSpace. The total number of Chinese papers was 2 993 and English papers 285. In terms of publication trend, the annual publication of English papers was low but showed an obvious upward trend, while the increase in Chinese papers fluctuated and tended to be flat. In terms of the content of Chinese papers published, TCM ranked first according to the discipline(2 415). In English papers, the number of publications in pharmacology and pharmaceutical science was the highest(87). Literature source analysis showed that the Chinese and English journals with the most publications were China Journal of Traditional Chinese Medicine and Pharmacy and Evidence Based Complementary and Alternative Medicine, respectively. Beijing University of Chinese Medicine published the most dissertations in China(99). The authors with the most publications in Chinese and English were LI Bin(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine) and LU Chuan-jian(Guangdong Hospital of Traditional Chinese Medicine). As revealed by the CiteSpace analysis of the research cooperation network, there were four mature and stable core teams in this field, but the cooperation intensity between different teams was weak. According to the keywords co-occurrence knowledge graph constructed by CiteSpace, the current hot keywords in this field are as follows: psoriasis, blood-heat syndrome, blood-stasis syndrome, fire needle, blood-dryness type, imiquimod, TCM bath, etiology and pathogenesis, cytokines, cupping therapy, etc. In summary, Chinese scholars have conducted active exploration and research in the field of TCM intervention in psoriasis in recent ten years. The overall development trend is good, and the breadth and depth of the research are constantly extending. It is suggested that relevant research should be free from discipline restrictions and strive for interdisciplinary integration.


Asunto(s)
Humanos , Medicina Tradicional China , Psoriasis/tratamiento farmacológico
16.
Artículo en Zh | WPRIM | ID: wpr-905861

RESUMEN

Objective:To seed for stable time window of the integrated disease-syndrome animal model based on the counterevidence from Chinese medicinal prescriptions, and to verify syndrome stability and reliability. Method:A model of depression was established by exposing rats to chronic unpredictable mild stress (CUMS), followed by body weight measurement, sugar water test, behavioral test, and brain 5-hydroxytryptamine(5-HT) detection. The identification of liver depression and spleen deficiency syndrome was conducted after the equivalent transformation of human clinical symptoms into macroscopic representations of rats. Based on the dynamically collected macroscopic representation scale, Xiaoyaosan was used to reversely verify the stability and reliability of the integrated disease-syndrome animal model of depression due to liver depression and spleen deficiency. Result:The sugar water consumption and the number of crossings and the total movement distance in the open field test of 16-week-old rats in the CUMS (eight weeks of CUMS) group were significantly lower than those in the normal group (<italic>P</italic><0.05). According to the immunohistochemical results, the 5-HT content in hippocampal area CA2 of rats in the CUMS group was also significantly lowered as compared with that in the normal group(<italic>P</italic><0.05),which indicated that depression was successfully modeled. The liver depression and spleen deficiency syndrome was present in 14-week-old rats (six weeks after CUMS)of the CUMS group, and the number of rats experiencing the liver depression and spleen deficiency syndrome reached the peak in the 16th week (eight weeks after CUMS),accounting for 70% of the total number. Thereafter, the number decreased gradually. The syndrome scores of the 14-, 16-, 18-, 20-, and 22-week-old rats in the Xiaoyaosan group were reduced by 66.6%, 70.7%, 54.8%, 50.4%, and 44.8%, which were graded as effective, marked effective, effective, effective, and effective, respectively. Conclusion:The age of 14-16 weeks(six to eight weeks after CUMS) is considered the stable and reliable time window for depression due to liver depression and spleen deficiency.

17.
National Journal of Andrology ; (12): 895-899, 2020.
Artículo en Zh | WPRIM | ID: wpr-880288

RESUMEN

Objective@#To investigate the application of the self-made semen quality control (QC) product in internal QC of computer-assisted sperm analysis (CASA).@*METHODS@#CASA was calibrated with high- and low-concentration commercially available semen QC product and meanwhile 15 samples of self-made mixed semen QC product were placed in 75 cryotubes containing liquid nitrogen, followed by CASA of the concentration, motility, curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), linearity (LIN), wobble (WOB) and straightness (STR) of the sperm using standard procedures and 50 days of continuous monitoring. The Makler counting plate was used to measure the concentration and motility of the self-made sperm.@*RESULTS@#The coefficients of variation (CV) of the commercially available semen QC product at high and low concentrations were 6.18% and 7.85%, respectively. CASA showed that the concentration of the self-made QC product was (25.97 ± 1.41) ×10⁶/ml, with a CV of 5.42%, and the sperm motility, VCL, VSL, VAP, LIN, WOB and STR were (22.15 ± 1.75)% (CV = 7.9%), (59.18 ± 2.05) μm/s (CV = 3.46%), (26.79 ± 1.2) μm/s (CV = 4.48%), (34.98 ± 1.4) μm/s (CV = 4.01%), 46.81 ± 1.55 (CV = 3.3%), 60.52 ± 1.3 (CV = 2.15%) and 76.46 ± 1.98 (CV = 2.59%), respectively. The concentration and motility of the self-made sperm detected with the Makler counting plate were (34.39 ± 2.37) ×10⁶/ml (CV = 6.89%) and (38.04 ± 1.69)% (CV = 4.44%), respectively. Levey-Jennings QC charts were plotted for the indicators using the means and standard deviation.@*CONCLUSIONS@#The self-made internal QC product by liquid nitrogen cryopreservation is feasible and effective for monitoring the accuracy and precision of CASA-derived sperm concentration and motion parameters, and it has a smaller CV than the commercially available QC product in measuring sperm concentration.


Asunto(s)
Humanos , Masculino , Computadores , Control de Calidad , Análisis de Semen/normas , Motilidad Espermática , Espermatozoides
18.
Artículo en Zh | WPRIM | ID: wpr-776661

RESUMEN

OBJECTIVE@#To investigate the use of antibiotics in children with community-acquired pneumonia (CAP) in multiple regions of China, and to provide a reference for CAP standard treatment and rational antibiotic use in children.@*METHODS@#The medical data of 1 383 children with CAP who were hospitalized in the department of pediatrics in 10 grade A tertiary hospitals from 9 cities between April 14, 2014 and January 1, 2016 were reviewed, to analyze the status of antibiotic use in hospitalized children in North China, Northeast China, East China, and South China.@*RESULTS@#The overall rate of antibiotic use in children with CAP was 89.08%, with 88.7% in North China, 95.5% in Northeast China, 83.3% in East China, and 86.6% in South China. The main types of antibiotics used were cephalosporins, macrolides, compound preparations of β-lactam antibiotics, polyphosphoric broad-spectrum antibiotics and other β-lactam antibiotics. The selection of antibiotics was generally rational, but antibiotics were still used in some patients with viral infection alone or a combined use of ≥2 kinds of antibiotics were noted in some patients with infection caused by one kind of pathogen. Irrational antibiotic use was observed in 131 children (10.63%).@*CONCLUSIONS@#There are high rates of antibiotic use and irrational use of antibiotics among children with CAP. Standard management of antibiotic use in children with CAP should be strengthened.


Asunto(s)
Niño , Humanos , Antibacterianos , Usos Terapéuticos , Niño Hospitalizado , China , Infecciones Comunitarias Adquiridas , Quimioterapia
19.
Chinese Medical Equipment Journal ; (6): 92-95,102, 2018.
Artículo en Zh | WPRIM | ID: wpr-699976

RESUMEN

The vaporized hydrogen peroxide had its applicability, mechanism and generation mode introduced, and its application was analyzed in the hospitals, bio-safety labs and etc in foreign countries and China. It's pointed out that emphases in China had to be placed on vaporized hydrogen peroxide concentration real-time monitoring when used for disinfection.The relationship was determined between vaporized hydrogen peroxide concentration and disinfection effect,and the studies were carried out on domestic production and automation of the vaporized hydrogen peroxide equipment. The vaporized hydrogen peroxide was indicated to gain a brilliant application prospect in the field of disinfection.

20.
Artículo en Zh | WPRIM | ID: wpr-700050

RESUMEN

The standards and norms of foreign countries were summarized for personal positive pressure protective equipment, and the involved protective clothing was introduced on the concept, classification, overall requirements, key parameters, materials, test methods and etc. China standards on positive pressure biological protective clothing were compared with those of foreign countries, and had their deficiencies analyzed deeply. It's pointed out that biosafety technologies with independent intellectual properties and standards on development and quality test of positive pressure biological protective clothing be emphasized on in the biosafety field. [Chinese Medical Equipment Journal,2018,39 (5):90-96]

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