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BACKGROUND: Hispolon, a phenolic compound isolated from the medicinal yellow fungal mulberry, exhibits a strong anti-triple-negative breast cancer (TNBC) effect. However, the antitumor mechanisms of Hispolon have not been fully explored. OBJECTIVE: In this study, we systematically investigated the mechanism of Hispolon against TNBC based on bioinformatics and in vitro experiments. METHODS: The Hispolon-related targets were first collected from the SwissTarget database. Differential Expression Genes (DEG) were screened between TNBC and normal breast tissue using the Gene Expression Comprehensive (GEO) dataset. The overlapping targets between Hispolon and DEG were analyzed by plotting Venn maps. Protein-protein interaction (PPI) network was constructed to analyze the interactions among these targets. The focus was on mining the core targets of anti-TNBC effects of Hispolon via the Cytohubba and MCODE plugin of Cytoscape 3.7.2 software. We performed survival analysis on these core targets to screen the best-matched targets, including EGFR, KIT, and PLAU. This correlated strongly with our validation of Hispolon by molecular docking. In addition, Gene Ontology (GO) anal-ysis and KEGG pathway analysis were performed using R software (ClusterProfiler package). Finally, in vitro experiments were performed to assess the accuracy of predicted target genes. RESULTS: The ADME results suggested that Hispolon has great potential to develop into a drug. Twenty overlapping targets were screened by matching the 107 targets of Hispolon to the 2,013 targets of TNBC DEG. Seven core targets of Hispolon against TNBC were initially identified, including EGFR, IGFBP3, MMP9, MMP2, MMP1, PLAU, and KIT. GO enrich-ment analysis demonstrated that the biological process of Hispolon acting on TNBC mainly involves lymphocyte activation in immune response and phosphatidylinositol-mediated signal-ing. Additionally, the relaxin signaling pathway, estrogen signaling pathway, proteoglycans in cancer, and others might be the key pathways of Hispolon against TNBC. Furthermore, Hispo-lon inhibited the proliferation of MDA-MB-231 cells in a concentration-dependent manner and regulated the RNA and protein expression of the core targets EGFR, PLAU, and KIT for the treatment of TNBC. CONCLUSION: In this study, the polygenic pharmacological mechanism of action of Hispolon against TNBC was explored through network pharmacology and in vitro experiments, provid-ing a new insight into the mechanism of TCM monomer against TNBC.
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Background: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disease associated with lipid metabolic disorders. Because of its clinical diversity and rarity, the diagnosis is often unclear. However, there is still a lack of reports on bibliometric analysis of CTX. The aim of this study was to assess the progress and research developments of CTX over the past three decades, identify emerging trends, and establish novel directions for future research. Methods: The eligible literature were screened from the Web of Science Core Collection (WoSCC) database. The annual publication, countries, institutions, authors, journals, keywords and references were visually analyzed by Microsoft Excel 2019, CiteSpace 6.2.R4, VOSviewer 1.6.18 and online bibliometrics website (https://bibliometric.com/). Results: A total of 561 publications from WoSCC were included in this study. The United States is the country with the largest number of publications, and Karolinska Institutet is the institution with the largest number of publications. Björkhem I. ranks as the most published and cited author in the last three decades. Journal of Lipid Research is the most widely published and cited journal. The strongest burst of keywords is "diagnosis." Conclusion: Unraveling the pathogenesis of CTX and improving its diagnosis and treatment continue to be critical challenges that require urgent attention. Future research endeavors will be centered on enhancing the efficiency and accuracy of early diagnosis and intervention.
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AIM: To comprehensively examine the associations of childhood and adulthood body size, and child-to-adult body size change with adult leucocyte telomere length (LTL). METHODS: We included 453 602 participants from the UK Biobank. Childhood body size at the age of 10 years was collected through a questionnaire. Adulthood body size was assessed using body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fat mass index (FMI), and fat-free mass index (FFMI). RESULTS: Individuals with plumper body size in childhood exhibited shorter LTL in adulthood (-0.0086 [-0.0017, -0.0004]). Adulthood BMI (-0.0286 [-0.0315, -0.0258]), WC (-0.0271 [-0.0303, -0.0238]), WHR (-0.0269 [-0.0308, -0.0230]) and FMI (-0.0396 [-0.0438, -0.0351]) were negatively associated with LTL, whereas FFMI (0.0095 [0.0039, 0.0152]) was positively associated with LTL. Compared to individuals consistently having an average/normal weight in both childhood and adulthood, those who maintained or developed overweight/obesity from childhood to adulthood had a shorter adult LTL, regardless of childhood body size. Notably, the LTL shortening effect was not observed in individuals with plumper body size in childhood but normal weight in adulthood. CONCLUSIONS: Childhood and adulthood obesity are both associated with LTL shortening in adulthood. Transitioning to or maintaining overweight/obese status from childhood to adulthood is associated with shorter adult LTL, whereas this effect can be reversed if plumper children become normal weight.
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AIM: To explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. METHODS: We included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. RESULTS: During a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche (<12 years, hazard ratio (HR) 1.08 [95 % confidence interval (CI) 1.02;1.13]), late menarche (≥15 years, HR 1.11 [1.04;1.17]), early menopause (<45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan (<30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity (≥4, HR 1.25 [1.17;1.34]), early age at first live birth (<20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. CONCLUSION: Our findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.
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INTRODUCTION: Chronic diabetic wounds pose a significant threat to the health of diabetic patients, representing severe and enduring complications. Globally, an estimated 2.5% to 15% of the annual health budget is associated with diabetes, with diabetic wounds accounting for a substantial share. Exploring new therapeutic agents and approaches to address delayed and impaired wound healing in diabetes becomes imperative. Traditional Chinese medicine (TCM) has a long history and remarkable efficacy in treating chronic wound healing. In this study, all topically applied proprietary Chinese medicines (pCMs) for wound healing officially approved by the National Medical Products Administration (NMPA) were collected from the NMPA TCM database. Data mining was employed to obtain a high-frequency TCM ingredients pair, Pearl-Borneol (1:1). METHOD: This study investigated the effect and molecular mechanism of the Pearl-Borneol pair on the healing of diabetic wounds by animal experiments and metabolomics. The results from animal experiments showed that the Pearl-Borneol pair significantly accelerated diabetic wound healing, exhibiting a more potent effect than the Pearl or Borneol treatment alone. Meanwhile, the metabolomics analysis identified significant differences in metabolic profiles in wounds between the model and normal groups, indicating that diabetic wounds had distinct metabolic characteristics from normal wounds. Moreover, Vaseline-treated wounds exhibited similar metabolic profiles to the wounds from the model group, suggesting that Vaseline might have a negligible impact on diabetic wound metabolism. In addition, wounds treated with Pearl, Borneol, and Pearl-Borneol pair displayed significantly different metabolic profiles from Vaseline-treated wounds, signifying the influence of these treatments on wound metabolism. Subsequent enrichment analysis of the metabolic pathway highlighted the involvement of the arginine metabolic pathway, closely associated with diabetic wounds, in the healing process under Pearl- Borneol pair treatment. Further analysis revealed elevated levels of arginine and citrulline, coupled with reduced nitric oxide (NO) in both the model and Vaseline-treated wounds compared to normal wounds, pointing to impaired arginine utilization in diabetic wounds. Interestingly, treatment with Pearl and Pearl-Borneol pair lowered arginine and citrulline levels while increasing NO content, suggesting that these treatments may promote the catabolism of arginine to generate NO, thereby facilitating faster wound closure. Additionally, borneol alone significantly elevated NO content in wounds, potentially due to its ability to directly reduce nitrates/nitrites to NO. Oxidative stress is a defining characteristic of impaired metabolism in diabetic wounds. RESULTS: The result showed that both Pearl and Pearl-Borneol pair decreased the oxidative stress biomarker methionine sulfoxide level in diabetic wounds compared to those treated with Vaseline, indicating that Pearl alone or combined with Borneol may enhance the oxidative stress microenvironment in diabetic wounds. CONCLUSION: In summary, the findings validate the effectiveness of the Pearl-Borneol pair in accelerating the healing of diabetic wounds, with effects on reducing oxidative stress, enhancing arginine metabolism, and increasing NO generation, providing a mechanistic basis for this therapeutic approach.
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Background: Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. Methods: To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. Results: In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. Conclusion: Collectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this article: This study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.
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Astaxanthin has 550 times more antioxidant activity than vitamin E, so it can scavenge free radicals in vivo and improve body immunity. However, the poor stability of astaxanthin becomes a bottleneck problem that limits its application. Herein, Haematococcus pluvialis (H. pluvialis) as a raw material was used to extract astaxanthin, and the optimal extraction conditions included the extraction solvent (EA:EtOH = 1:6, v/v), extraction temperature (60 °C), and extraction time (70 min). The extracted astaxanthin was then loaded using lecithin to form corresponding liposomes via the ethanol injection method. The results showed that the particle size and zeta potential of the prepared liposomes were 105.8 ± 1.2 nm and -38.0 ± 1.7 mV, respectively, and the encapsulation efficiency of astaxanthin in liposomes was 88.83%. More importantly, the stability of astaxanthin was significantly improved after being embedded in the prepared liposomes.
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Lipossomos , Xantofilas , Xantofilas/isolamento & purificação , Xantofilas/química , Lipossomos/química , Tamanho da Partícula , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Clorófitas/química , Clorofíceas/químicaRESUMO
Objective: This study aimed to determine the sensitivity and specificity of metagenomic next-generation sequencing (mNGS) for detecting pathogens in spinal infections and to identify the differences in the diagnostic performance between mNGS and targeted next-generation sequencing (tNGS). Methods: A total of 76 consecutive patients with suspected spinal infections who underwent mNGS, culture, and histopathological examinations were retrospectively studied. The final diagnosis of the patient was determined by combining the clinical treatment results, pathological examinations, imaging changes and laboratory indicators. The sensitivity and specificity of mNGS and culture were determined. Results: The difference between the two detection rates was statistically significant (p < 0.001), with mNGS exhibiting a significantly higher detection rate (77.6% versus 18.4%). The average diagnosis time of mNGS was significantly shorter than that of bacterial culture (p < 0.001, 1.65 versus 3.07 days). The sensitivity and accuracy of mNGS were significantly higher than that of the culture group (p < 0.001, 82.3% versus 17.5%; 75% versus 27.6%), whereas the specificity of mNGS (42.9%) was lower than that of the culture group (p > 0.05, 42.9% versus 76.9%). The sensitivity, specificity, accuracy, and positive predictive value (PPV) of pus were higher than those of tissue samples for mNGS, whereas for culture, the sensitivity, specificity, accuracy, and PPV of tissue samples were higher than those of pus. tNGS demonstrated higher sensitivity and accuracy in diagnosing tuberculosis (TB) than mNGS (80% versus 50%; 87.5% versus 68.8%). Conclusion: mNGS for spinal infection demonstrated better diagnostic value in developing an antibiotic regimen earlier, and it is recommended to prioritize pus samples for testing through mNGS. Moreover, tNGS outperformed other methods for diagnosing spinal TB and identifying antibiotic-resistance genes in drug-resistant TB.
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Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Sensibilidade e Especificidade , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenômica/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Técnicas de Diagnóstico Molecular/métodos , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/classificação , Doenças da Coluna Vertebral/diagnóstico , Doenças da Coluna Vertebral/microbiologia , Idoso de 80 Anos ou mais , AdolescenteRESUMO
Eucommia ulmoides Oliv. (tu-chung), as a famous nature medical and edible plant, has the effect of tonifying liver and kidney, strengthening the function of the muscles and bones, and miscarriage prevention. Accumulating evidence has demonstrated that the polysaccharides from Eucommia ulmoides Oliv. (EUPs) are a kind of vital and representative biologically active macromolecules and have various health-promoting biological activities in vivo and in vitro, such as antioxidant activity, immunomodulatory activity, hypolipidemic and hypoglycemic activities, anti-inflammatory activities, anti-tumor activity, and among others. The review aims to comprehensively and systematically collate the recent research progress on extraction and purification methods, structural characteristics, biological activities, mechanism of action, structural modification, and toxicity of EUPs to support their therapeutic potential and health-care functions. New valuable insights for future research with EUPs were also proposed in the areas of structural characterization and pharmacological activities to promoting the development of therapeutic agents and functional foods.
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Eucommiaceae , Polissacarídeos , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Eucommiaceae/química , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificaçãoRESUMO
Background: Epidemiological reports indicate a potential association between androgenic alopecia (AGA) and increased prostate cancer (PC) prevalence, but conflicting reports also exist. This study aims to elucidate the causality of AGA on PC risk using Mendelian randomization (MR) analysis. Materials and methods: Two-sample MR analyses utilized public genome-wide association studies summary data for single-nucleotide polymorphisms associated with AGA. Four statistical methods were used: inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, with IVW as the preliminary estimation method. Additionally, sensitivity analyses were conducted to address pleiotropic bias. Results: Genetically proxied AGA did not demonstrate a causal effect on PC risk (IVW P > 0.05). Consistently, complementary methods yielded results aligned with IVW. Conclusions: Our MR analysis indicates no causal relationship between genetically predicted AGA and PC risk, suggesting that observed associations in epidemiological studies may not be causal.
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Selenium (Se) is an essential trace element for humans. Low concentrations of Se can promote plant growth and development. Enhancing grain yield and crop Se content is significant, as major food crops generally have low Se content. Studies have shown that Se biofortification can significantly increase Se content in plant tissues. In this study, the genetic transformation of wheat was conducted to evaluate the agronomic traits of non-transgenic control and transgenic wheat before and after Se application. Se content, speciation, and transfer coefficients in wheat grains were detected. Molecular docking simulations and transcriptome data were utilized to explore the effects of selenium-binding protein-A TaSBP-A on wheat growth and grain Se accumulation and transport. The results showed that TaSBP-A gene overexpression significantly increased plant height (by 18.50%), number of spikelets (by 11.74%), and number of grains in a spike (by 35.66%) in wheat. Under normal growth conditions, Se content in transgenic wheat grains did not change significantly, but after applying sodium selenite, Se content in transgenic wheat grains significantly increased. Analysis of Se speciation revealed that organic forms of selenomethionine (SeMet) and selenocysteine (SeCys) predominated in both W48 and transgenic wheat grains. Moreover, TaSBP-A significantly increased the transfer coefficients of Se from solution to roots and from flag leaves to grains. Additionally, it was found that with the increase in TaSBP-A gene overexpression levels in transgenic wheat, the transfer coefficient of Se from flag leaves to grains also increased.
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Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas , Proteínas de Ligação a Selênio , Selênio , Selenito de Sódio , Triticum , Triticum/genética , Triticum/metabolismo , Triticum/crescimento & desenvolvimento , Proteínas de Ligação a Selênio/metabolismo , Proteínas de Ligação a Selênio/genética , Selênio/metabolismo , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Selenito de Sódio/metabolismo , Grão Comestível/metabolismo , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Simulação de Acoplamento Molecular , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Sementes/genética , Sementes/efeitos dos fármacosRESUMO
BACKGROUND: Antibiotic resistance is a serious global public health issue. However, there are few reports on trends in antimicrobial susceptibility in Chinese neonates, and most of the existing evidence has been derived from adult studies. We aimed to assess the trends in antimicrobial susceptibility of common pathogens in full-term neonates with invasive bacterial infections (IBIs) in China. METHODS: This cross-sectional survey study analyzed the antimicrobial susceptibility in Chinese neonates with IBIs from 17 hospitals, spanning from January 2012 to December 2021. Joinpoint regression model was applied to illustrate the trends and calculate the average annual percentage change (AAPC). Using Mantel-Haenszel linear-by-linear association chi-square test, we further compared the antibiotic minimum inhibitory concentrations (MICs) by pathogens between 2019 and 2021 to provide precise estimates of changes. RESULTS: The proportion of Escherichia coli with extended-spectrum-beta-lactamase-negative strains increased from 0.0 to 88.5% (AAPC = 62.4%, 95% confidence interval (CI): 44.3%, 82.9%), with two breakpoints in 2014 and 2018 (p-trend < 0.001). The susceptibility of group B Streptococcus (GBS) to erythromycin and clindamycin increased by 66.7% and 42.8%, respectively (AAPC = 55.2%, 95% CI: 23.2%, 95.5%, p-trend = 0.002; AAPC = 54.8%, 95% CI: 9.6%, 118.6%, p-trend < 0.001), as did Staphylococcus aureus to penicillin (AAPC = 56.2%; 95% CI: 34.8%, 81.0%, p-trend < 0.001). However, the susceptibility of Enterococcus spp. to ampicillin declined from 100.0 to 25.0% (AAPC = - 11.7%, 95% CI: - 15.2%, - 8.1%, p-trend < 0.001), and no significant improvement was observed in the antibiotic susceptibility of Escherichia coli to ampicillin, gentamicin, and cephalosporin. Additionally, the proportion of GBS/Staphylococcus aureus with relatively low MIC values for relevant antibiotics also increased in 2021 compared to 2019. CONCLUSIONS: Antimicrobial susceptibility of the most prevalent pathogens in full-term neonates seemed to have improved or remained stable over the last decade in China, implying the effectiveness of policies and practice of antibiotic stewardship had gradually emerged.
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Antibacterianos , Testes de Sensibilidade Microbiana , Humanos , Recém-Nascido , China/epidemiologia , Estudos Transversais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Feminino , Masculino , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Streptococcus agalactiae/efeitos dos fármacos , População do Leste AsiáticoRESUMO
Depression is closely related to individual social functions. The current study aimed to examine whether depression is associated with ostracism, whether interpretation bias mediates this relationship, and whether trait mindfulness moderates direct and indirect relationships between depression and ostracism. Overall, 389 Chinese college students completed the Center for Epidemiological Survey, Depression Scale, Interpretation Bias Questionnaire, Philadelphia mindfulness scale, and perceived ostracism scale at two-time points. Latent Profile analysis and moderated mediation analysis were performed. After controlling for sex and age, depression (t1) was positively correlated to perceived ostracism, with this relationship being partially mediated by negative interpretation bias (IBN, t2). The effect of IBN on perceived ostracism was weak when awareness was high at time 2. Acceptance had a non-significant moderating role in the relationship between IBN and perceived ostracism at time 2. LPA delineated three profiles: high awareness, high acceptance, and medium mindfulness. The moderating role of the different profiles in the relationship between IBN (t2) and perceived ostracism (t2) was significant. Depressed individuals appear to experience more ostracism because of IBN. Awareness might alleviate the effect of IBN on perceived ostracism.
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This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential.
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OBJECTIVE: To investigate the effect of saline perfusion before catheter removal in patients with benign prostatic hyperplasia (BPH) treated with GreenLight laser photoselective vaporization of the prostate (PVP). MATERIALS AND METHODS: Patients (n=200) with BPH treated with PVP were divided into perfusion (n=100) and control (n=100) groups. For the perfusion group, saline (200 mL or the maximum capacity tolerated) was irrigated into the bladder after standardized external urethral disinfection, and the catheter was removed. Catheter removal was routinely performed in the control group. Perioperative adverse events and clinical outcomes were compared between the groups. RESULTS: Patients in the perfusion group had a shorter waiting time [3 (0-4) vs. 15 (8.75-26) min; P<0.001] and a better satisfaction grade [24 (21.75-26) vs. 23 (20-25); P=0.016] for first urination than those in the control group. The perfusion group exhibited lower anxiety levels regarding first urination than the control group [1 (1-2) vs. 1.5 (1-2), respectively; P=0.012]. Urinalysis revealed that the perfusion group had significantly lower white blood cell (WBC) count than the control group on the day [25.5 (8-37.75) vs. 43.5 (24.0-64.75); P<0.001] and 2 weeks [20.5 (11-27) vs. 31.0 (20-42); P<0.001] after catheter removal. No significant differences in treatment-related adverse events were observed [perfusion (n=15), control (n=20)]. CONCLUSION: Saline perfusion before catheter removal in patients with BPH treated with PVP could shorten the waiting time for first urination, improve patient anxiety and satisfaction and reduce postoperative urinary WBC levels.
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Objective: To evaluate the safety and efficacy of 180-W XPS Greenlight laser "Five-step" photoselective vaporization of the prostate (PVP) in patients with benign prostatic hyperplasia (BPH) with prostate volume (PV) > 80 mL. Background: In patients with BPH with large PV, PVP often results in bleeding, unclear visual field, additional damage, and insufficient tissue vaporization. Methods: This single-center, retrospective study enrolled patients with BPH with PV > 80 mL treated with the Five-step PVP or the Conventional PVP from January 2018 to June 2021. Comorbidities, high-risk habits, and operative parameters were analyzed and compared. The short-term functional outcomes and postoperative complications were recorded over the 24-month follow-up. Results: Two hundred eligible patients were divided into the Five-step PVP and Conventional PVP groups (n = 100 each). These groups showed no differences in comorbidities, living habits, baseline perioperative parameters, operative time, lasing time, or energy use. However, a higher energy density (3.95 [interquartile range (IQR) 3.37, 4.52] vs 3.68 [IQR 3.17, 4.20] kJ/mL) and energy-time ratio (7.23 [IQR 6.12, 8.52] vs 6.72 [IQR 5.51, 7.87] kj/min p = 0.034) were obtained in the Five-step PVP group. Subgroup analysis of patients with PV ≥120 mL showed similar results. The short-term functional outcomes were similar between the two study groups with significant improvement from baseline, but the total prostate-specific antigen levels at 1 and 6 months were lower in the Five-step PVP group. Further, incidences of intraoperative bleeding, bladder mucosa injury, postoperative hematuria, and urinary tract infection were lower in the Five-step PVP group. In the Conventional PVP group, four patients required conversion to transurethral resection of the prostate in surgery and two patients required retreatment during the 24-month follow-up. Conclusions: The 180-W XPS Greenlight laser Five-step PVP has advantages of less bleeding, high vaporization efficiency, and low rates of perioperative complications, and, therefore, it is a promising treatment to improve short-term functional outcomes for patients with BPH with large PV.
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Bacillus genus, particularly Bacillus velezensis, is increasingly considered as viable alternatives to antibiotics in aquaculture due to their safety and probiotic potential. However, the specific mechanisms through which probiotic B. velezensis confers protection against Aeromonas hydrophila infection in fish remain poorly understood. This study delved into the multifaceted impacts of B. velezensis BV1704-Y on diverse facets of zebrafish health, including gut barrier function, immune response, oxidative stress, gut environment, microbiome composition, and disease resistance. Our findings demonstrate that supplementation with B. velezensis BV1704-Y significantly alleviated symptoms and reduced mortality in zebrafish infected with A. hydrophila. Furthermore, a notable reduction in the expression of pivotal immune-related genes, such as IL-1ß, IL6, and TNF-α, was evident in the gut and head kidney of zebrafish upon infection. Moreover, B. velezensis BV1704-Y supplementation resulted in elevated activity levels of essential antioxidant enzymes, including SOD, CAT, and GSH, in gut tissue. Notably, B. velezensis BV1704-Y positively modulated the structure and function of the intestinal microbiome, potentially enhancing immune response and resilience in zebrafish. Specifically, supplementation with B. velezensis BV1704-Y promoted the relative abundance of beneficial bacteria, such as Cetobacterium, which showed a noteworthy negative correlation with the expression of pro-inflammatory genes and a positive correlation with gut barrier-related genes. Altogether, our study suggests that B. velezensis BV1704-Y holds promise as an effective probiotic for protecting zebrafish against A. hydrophila infection, offering potential benefits for the aquaculture industry.
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Aeromonas hydrophila , Bacillus , Resistência à Doença , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Probióticos , Peixe-Zebra , Animais , Aeromonas hydrophila/fisiologia , Peixe-Zebra/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Doenças dos Peixes/imunologia , Probióticos/farmacologia , Probióticos/administração & dosagem , Bacillus/química , Bacillus/fisiologia , Resistência à Doença/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Ração Animal/análise , Dieta/veterinária , Imunidade InataRESUMO
BACKGROUND: Artificially sweetened beverages (ASB) are consumed globally, but their impact on overall health remains uncertain. We summarized published associations between ASB intake with all-cause and cause-specific mortality. METHODS: We searched Medline, Embase, Web of Science, and Cochrane CENTRAL databases until August 2023. Random effect meta-analysis was conducted to calculate pooled risk ratios (RRs) and 95% confidence intervals (95%CIs) for highest versus lowest categories of ASB consumption in relation to all-cause and cause-specific mortality. Linear and non-linear dose-response analyses were also performed. RESULTS: Our systematic review and meta-analysis included 11 prospective cohort studies. During a median/mean follow-up period of 7.0 to 28.9 years, 235,609 deaths occurred among 2,196,503 participants. Intake of ASB was associated with higher risk of all-cause and CVD mortality with pooled RRs (95%CIs) of highest vs. lowest intake categories of 1.13 (1.06, 1.21) (I2 = 66.3%) for all-cause mortality and 1.26 (1.10, 1.44) (I2 = 52.0%) for CVD mortality. Dose-response analysis revealed a non-linear association of ASB with all-cause mortality (pnon-linearity = 0.01), but a linear positive association with CVD mortality (pnon-linearity = 0.54). No significant association was observed for ASB intake and cancer mortality. Moreover, a secondary meta-analysis demonstrated that replacing 1 serving/day of sugary sweetened beverages (SSB) with ASB was associated with 4-6% lower risk of all-cause and CVD mortality. Per NutriGrade, the evidence quality for associations between ASB intake with all-cause and CVD mortality was moderate. CONCLUSIONS: Higher intake of ASB was associated with higher risk of all-cause and CVD mortality, albeit a lower risk than for SSB. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022365701.
Assuntos
Bebidas Adoçadas Artificialmente , Humanos , Bebidas Adoçadas Artificialmente/estatística & dados numéricos , Estudos Prospectivos , Doenças Cardiovasculares/mortalidade , Causas de Morte , Mortalidade/tendências , Edulcorantes/administração & dosagem , Edulcorantes/efeitos adversosRESUMO
Objective Our objective was to investigate the basic information of the personnel and facilities of nuclear medicine in Beijing. Methods This survey was performed by the Beijing Quality Control Center in 2018. The investigation included personnel, equipment, and clinical applications, and data were then compared with previous surveys. The paper questionnaires were used for the survey, which required information about the personnel, devices, and clinical applications. Results About 38 nuclear medicine departments in Beijing were involved in the survey. The number of nuclear medicine staff was 531 in 2018, showing an increase of 58.7% over the past decade. Positron emission tomography/computed tomography (PET/CT), single-photon emission computed tomography (SPECT), and single-photon emission computed tomography/computed tomography (SPECT/CT) represented the main nuclear medicine facilities, and the total number of surveyed departments was 18, 24, and 34, respectively. The quality control results showed significant improvement from the 2005 levels. The total number of scintigraphy procedures was estimated at 199,607 (153,185 SPECT and 46,422 PET/CT). The estimated annual number of scintigraphy images was 8.9 per 1,000 population for SPECT and 2.7 per 1,000 population for PET/CT during 2018. The most frequent radioiodine-targeted therapy was 131 I-targeted therapy for hyperthyroidism in 2018. Conclusion Nuclear medicine has experienced rapid growth in the past 10 years in Beijing, either in personnel, equipment, and scintigraphy. Future efforts will focus on the use of new isotopes in the diagnosis, implementing quality strategy, and enhancing training.