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1.
BMJ Open ; 14(10): e085789, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39366715

RESUMO

OBJECTIVES: This study aimed to investigate the satisfaction levels of graduate residents in Guizhou Province and analyse the factors influencing their satisfaction. METHODS: A cross-sectional survey was conducted using a simple random sampling method with all graduate residents from 24 hospitals in Guizhou Province. The survey covered the residents' demographic information, information about the training hospitals and satisfaction survey responses. Statistical analyses were performed using SPSS 29.0, including descriptive statistics using component ratios, binomial distribution tests for specific satisfaction situations, X 2 tests for between-group comparisons and binary logistic regression analyses to analyse the associations between residency satisfaction and related factors. The significance level was set at α=0.05. RESULTS: The survey included 1070 graduate residents of Guizhou Province, China, including 500 males (46.7%) and 570 females (53.3%). The satisfaction questionnaire revealed that 23.8% were very satisfied; 45.4% were somewhat satisfied; and 26.4%, 2.3% and 2.1% were average, somewhat dissatisfied and very dissatisfied, respectively. Factors influencing residency satisfaction included gender, age, training base level, identity type, training participation year and average monthly income. CONCLUSION: Based on this study, the satisfaction of graduate residents in Guizhou Province, China, is relatively lower than that in other countries and provinces. Therefore, Guizhou Province should take appropriate measures to address these influencing factors and enhance residency training satisfaction, thereby improving the residency training quality.


Assuntos
Internato e Residência , Satisfação Pessoal , Humanos , China , Feminino , Masculino , Internato e Residência/estatística & dados numéricos , Estudos Transversais , Adulto , Inquéritos e Questionários
3.
Microbiol Spectr ; 12(10): e0288123, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39162262

RESUMO

Microorganisms are vital for the health of marine invertebrates, and their assembly is driven by both deterministic and stochastic factors that regulate residents (innate to the host) and transients (from ambient water). However, the role of water microbiota and the significance of deterministic and stochastic processes in aquatic hosts facing mortality threats are largely unknown. This study examines the shifts in water microbiota during an oyster mortality event using amplicon sequencing and compared with those of resident oysters to disentangle the balance of the deterministic and stochastic factors involved. Water temperature and dissolved oxygen significantly shape the microbial community with a distinct monthly pattern, and Cyanobacteria blooms might exacerbate oyster mortality. The comparative analysis of microbial communities in oysters and water revealed that ≤ 21% of the genera were shared between oysters and water, implying that water microbiota cannot easily transfer into oysters. Furthermore, these shared genera had different functions, with oysters more involved in promoting host digestion and nutrient acquisition and water bacteria enriched more in functions promoting their own growth and survival. These findings illustrate that oysters may possess specific selection or barrier mechanisms that permit a small percentage of transients, controlled by stochastic factors and having a minimal effect on oyster mortality, to enter, whereas the majority of oyster microbiota are residents governed by deterministic factors. Consequently, oysters exhibit some plasticity in their symbiotic microbiota, enabling them to maintain microbial homeostasis and adapt to complex microbial surroundings. This may be a shared mechanism among marine invertebrates for survival in complex marine environments.IMPORTANCEPacific oysters are widely cultured and play vital ecological roles. However, the summer mortality hinders sustainable oyster farming. Untangling causative mechanisms of oyster mortality is a complex task due to the intricate "interactome" involving environmental factors, hosts, and pathogens. Interactions between hosts and microorganisms offer an ideal avenue for investigating the truth. We systematically investigated the microbial community in water and resident oysters during a summer mortality event and proposed that the assembly of oyster microbiota is primarily governed by deterministic processes independent of mortality. Pathogens mainly originate from resident members of the oyster microbiota, with a limited influence from the microbial community in the water. Additionally, environmental degraders, such as Cyanobacteria blooms, cannot be overlooked as a contributing factor of oyster mortality. This study evaluated the weight of deterministic and stochastic factors in microbial assembly during an oyster mortality event and greatly broadened our understanding of the "interactome" through the interaction between oysters and water in microbiota.


Assuntos
Bactérias , Microbiota , Ostreidae , Microbiologia da Água , Animais , Microbiota/fisiologia , Ostreidae/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Água do Mar/microbiologia , Cianobactérias/genética , Cianobactérias/fisiologia , Cianobactérias/crescimento & desenvolvimento , Temperatura
4.
iScience ; 27(8): 110562, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39175775

RESUMO

The interaction between prostate cancer (PCa) cells and prostate stromal cells fosters an immunosuppressive tumor microenvironment (TME) that promotes tumor growth and immune evasion. However, the specific signaling pathways involved remain unclear. We identified a key mechanism involving the CXCL5/CXCR2 and LIF/LIFR pathways, which create a feedforward loop that enhances neuroendocrine differentiation (NED) in PCa cells and upregulates WNT1-inducible signaling pathway protein 1 (WISP1) in both cell types. WISP1 upregulation is essential for inducing immune checkpoints and immunosuppressive cytokines via LIF/LIFR signaling and STAT3 phosphorylation. This process leads to increased neuroendocrine markers, immune checkpoints, cell proliferation, and migration. Notably, WISP1 levels in patient sera correlate with PCa progression, suggesting its potential as a biomarker. Our findings elucidate the mechanisms by which reciprocal communication between PCa cells and stromal cells contributes to the formation of an immunosuppressive TME, driving the malignant progression of PCa and highlighting potential targets for therapeutic intervention.

6.
Cancer Lett ; 598: 217090, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945201

RESUMO

The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective immune responses. The interleukin-1 (IL-1) receptor antagonist (IL1RN), a key anti-inflammatory molecule, plays a significant role in suppressing IL-1-related immune and inflammatory responses. Our research investigates the oncogenic role of IL1RN in PCa, particularly its interactions with muscarinic acetylcholine receptor 4 (CHRM4), and its involvement in driving immunosuppressive pathways and M2-like macrophage polarization within the PCa TME. We demonstrate that following androgen deprivation therapy (ADT), the IL1RN-CHRM4 interaction in PCa activates the MAPK/AKT signaling pathway. This activation upregulates the transcription factors E2F1 and MYCN, stimulating IL1RN production and creating a positive feedback loop that increases CHRM4 abundance in both PCa cells and M2-like macrophages. This ADT-driven IL1RN/CHRM4 axis significantly enhances immune checkpoint markers associated with neuroendocrine differentiation and treatment-resistant outcomes. Higher serum IL1RN levels are associated with increased disease aggressiveness and M2-like macrophage markers in advanced PCa patients. Additionally, elevated IL1RN levels correlate with better clinical outcomes following immunotherapy. Clinical correlations between IL1RN and CHRM4 expression in advanced PCa patients and neuroendocrine PCa organoid models highlight their potential as therapeutic targets. Our data suggest that targeting the IL1RN/CHRM4 signaling could be a promising strategy for managing PCa progression and enhancing treatment responses.


Assuntos
Diferenciação Celular , Proteína Antagonista do Receptor de Interleucina 1 , Neoplasias da Próstata , Microambiente Tumoral , Masculino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Animais , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Macrófagos/metabolismo , Macrófagos/imunologia , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F1/genética
7.
JHEP Rep ; 6(6): 101032, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38882603

RESUMO

Background & Aims: Previous studies demonstrated oxytocin treatment effectiveness in reducing mortality and reversing liver fibrosis in mice. However, the underlying mechanism remains obscure, given the absence of oxytocin receptor expression in hepatic stellate cells, the primary liver fibrosis effector cells. Methods: A comprehensive map of cell populations in fibrotic liver was generated using single-cell sequencing. The map enabled our study of the target cells of oxytocin action in the liver in more dimensions. Furthermore, we elucidated the mechanism of the oxytocin signaling system in hepatic macrophages using oxytocin receptor-specific knockout mice and liver fibrosis animal models. Results: The carbon tetrachloride-induced hepatic fibrosis and bile duct ligation hepatic fibrosis mouse models demonstrated that oxytocin reversed hepatic fibrosis in mice. The mapped liver cell populations demonstrated that oxytocin promoted the phenotypic switch from Ly6high to Ly6Clow in myeloid-derived macrophages. The phenotypic control of oxytocin signaling system activation on this phenotypic switch was validated using myeloid-specific oxytocin receptor knockout mice. Subsequent studies demonstrated that the calcium inward flow induced by oxytocin receptor activation activated the key orphan nuclear receptor NR4A1, which controls macrophage phenotypic switching. Specifically, calcium ions activated CREB, a key target regulator of NR4A1 expression. Conclusions: The findings established hepatic macrophages as a hub responsible for the oxytocin-mediated alleviation of liver fibrosis. This study revealed a novel pathway where oxytocin regulates macrophage phenotype. Impact and implications: Previous studies revealed for the first time the expression of oxytocin receptors in the liver. The present study shows that oxytocin reverses hepatic fibrosis and that hepatic macrophages are the central hub of oxytocin-mediated alleviation of hepatic fibrosis by promoting a phenotypic switch in hepatic macrophages, transitioning from Ly6high to Ly6Clow expression. The present study reveals a novel pathway by which oxytocin regulates macrophage phenotype. In addition, the potential applications of oxytocin and its analogues, as traditional drugs for clinical application, in the treatment of liver fibrosis deserve to be further explored.

8.
Aging (Albany NY) ; 16(8): 6868-6882, 2024 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-38613803

RESUMO

OBJECTIVE: The study aims to examine the involvement of lincRNA00907 in the advancement of non-alcoholic steatohepatitis (NASH). METHODS: The examination was conducted to assess the expression of linc00907 in liver tissues from NASH patients and healthy individuals. High-fat diets induced NASH in mouse models, while palmitic acid/oleic acid treatment was used to create in vitro cell models. Various techniques, such as qRT-PCR, Oil Red O staining and gene knockdown/overexpression, were used to assess the impact of linc00907 on genes related to lipid metabolism and immunity, as well as intracellular lipid accumulation. Furthermore, dual-luciferase reporter assays were carried out to confirm the connection between miRNA-942-5p and linc00907 or TAOK1 mRNA. RESULTS: Linc00907 was found to be significantly upregulated in both NASH patients and NASH mouse models. Overexpression of linc00907 led to an increase in intracellular lipid accumulation, while knockdown of linc00907 resulted in decreased lipid content. It was found that miRNA-942-5p binds with linc00907, and their interaction was confirmed in dual-luciferase reporter assays. Additionally, TAOK1 was predicted to be a downstream target of miRNA-942-5p, and the upregulation of TAOK1 due to linc00907 was reversed by miRNA-942-5p overexpression. linc00907 overexpression reduces apoptosis but can be reversed by TAOK1 knockdown. The reduction of TAOK1 counteracted the impact of linc00907 on gene expression associated with lipid metabolism and immunity, as well as on the accumulation of intracellular lipids. CONCLUSIONS: Our research suggests that linc00907 functions as a competitive endogenous RNA (ceRNA) by sequestering miRNA-942-5p, thus increasing the expression of TAOK1 and encouraging lipid accumulation in hepatocytes, leading to the aggravation of NASH development. Targeting the linc00907/miRNA-942-5p/TAOK1 axis may hold therapeutic potential for the treatment of NASH.


Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica , RNA Longo não Codificante , Animais , Humanos , Masculino , Camundongos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
9.
J Affect Disord ; 354: 603-610, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38503356

RESUMO

BACKGROUND: Previous observational studies have highlighted potential links between the consumption of processed meat and red meat (such as pork, mutton, and beef intake) and the occurrence of mental disorders. However, it is unclear whether a causal association exists. Therefore, we employed the Mendelian randomization (MR) study to investigate the causal effects of genetically predicted processed meat and red meat on mood disorders (MD), anxiety disorders (AD), and major depressive disorder (MDD). METHODS: Genetic instruments for processed and red meat were selected from the Genome-Wide Association Study (GWAS) of the UK Biobank Study. Their associations with MD (42,746 cases 254,976), AD (35,385 cases and 254,976 controls), and MDD (38,225 cases and 299,886 controls) were obtained from the FinnGen Consortium. The inverse variance weighted (IVW) method was the primary method for two-sample MR analysis. Additionally, we employed complementary analysis to assess the robustness of our MR findings (eg, MR Egger and weighted median). We also conducted multiple sensitivity analyses to investigate horizontal pleiotropy and heterogeneity. Moreover, we performed a univariate and multivariable MR (MVMR) study to evaluate these associations. RESULTS: In our univariate MR analysis, we observed that genetically predicted beef intake was associated with a reduced risk of MD [odds ratio (OR) = 0.403, 95 % confidence interval (CI) = 0.246-0.659; PIVW = 4.428 × 10-5], AD (OR = 0.443, 95 % CI = 0.267-0.734; PIVW = 1.563 × 10-3), and MDD (OR = 0.373, 95 % CI = 0.216-0.643; PIVW = 3.878 × 10-4). After adjusting for processed meat, pork, and mutton intake in the MVMR analysis, the protective association of beef intake against MD and MDD remained. However, there was no substantial evidence indicating a significant causal relationship between processed meat, pork, and mutton intake and the occurrence of mental disorders. Furthermore, our sensitivity analysis revealed no significant evidence of horizontal pleiotropy. CONCLUSION: These findings support a causal relationship between genetically predicted beef intake and reducing the risk of MD and MDD.


Assuntos
Transtorno Depressivo Maior , Transtornos Mentais , Carne Vermelha , Bovinos , Animais , Humanos , Análise da Randomização Mendeliana , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Carne , Carne Vermelha/efeitos adversos
10.
Mol Oncol ; 18(6): 1665-1686, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38381121

RESUMO

Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT-driven LIF/LIFR signaling induces brain-derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration-resistant PCa (CRPC) and a positive correlation with programmed death-ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Neoplasias da Próstata , Microambiente Tumoral , Masculino , Humanos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/imunologia , Linhagem Celular Tumoral , Microambiente Tumoral/imunologia , Transdução de Sinais/efeitos dos fármacos , Fator Inibidor de Leucemia/metabolismo , Células Estromais/metabolismo , Células Estromais/patologia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/metabolismo , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/genética , Animais , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/imunologia , Diferenciação Celular
11.
Phytomedicine ; 126: 155148, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387271

RESUMO

BACKGROUND: Finding a drug for early intervention in the hepatic fibrosis process has important clinical significance. Previous studies have suggested SUMOylation as a potential target for intervention in hepatic fibrosis. However, the role of SAE1, a marker of SUMOylation, in hepatic fibrosis is unknown. Additionally, whether ginkgolic acid (GA), a SUMOylation inhibitor, inhibits hepatic fibrosis by inhibiting SUMO1-activating enzyme subunit 1 (SAE1) should be further investigated. METHODS: Liver tissues of patients with hepatic cirrhosis and a rat model of hepatic fibrosis constructed with CCl4 (400 mg/kg, twice weekly) or TAA (200 mg/kg, twice weekly) were selected, and the degree of hepatic fibrosis was then evaluated using H&E, Sirius red, and Masson's trichrome staining. After knockdown or overexpression of SAE1 in hepatic stellate cells, the expression levels of ferroptosis and hepatic fibrosis markers were measured in vitro. After intervention with a ferroptosis inhibitor, the expression levels were again measured in vivo and in vitro. RESULTS: We first demonstrated that SAE1 increased in patients with hepatic cirrhosis. Subsequently, testing of the rat hepatic fibrosis model confirmed that GA reduced the expression of SAE1 and improved hepatic fibrosis in rats. Then, we used hepatic stellate cell lines to confirm in vitro that GA inhibited SAE1 expression and induced ferroptosis, and that overexpression of SAE1 or inhibition of ferroptosis reversed this process. Finally, we confirmed in vivo that GA induced ferroptosis and alleviated the progression of hepatic fibrosis, while inhibiting ferroptosis also reversed the progression of hepatic fibrosis in rats. CONCLUSION: SAE1 is a potential anti-fibrotic target protein, and GA induces ferroptosis of hepatic stellate cells by targeting SAE1 to exert an anti-hepatic fibrosis effect, which lays an experimental foundation for the future clinical application of its anti-hepatic fibrosis effect.


Assuntos
Ferroptose , Salicilatos , Humanos , Ratos , Animais , Transdução de Sinais , Cirrose Hepática/metabolismo , Fígado , Células Estreladas do Fígado , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas Ativadoras de Ubiquitina/farmacologia
12.
Int Dent J ; 74(4): 876-883, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38238210

RESUMO

INTRODUCTION: During dental treatment procedures ultrasonic scalers generate droplets containing microorganisms such as bacteria and viruses. Hence, it is necessary to study the dynamic properties of generated droplets in order to investigate the risks associated with the spread of infection. The aim of this study was to visualise the flow state of droplets and to evaluate the impact of droplets generated during the use of an ultrasonic scaler during an oral surgical procedure. METHODS: We studied the spatial flow of liquid droplets through a combination of imaging and numeric simulation of a simulated dental treatment processes. First, we photographed the real time images of the ultrasonic scaler and evaluated the images using image-processing software Image J to visualise the flow of liquid droplets. Finally we simulated the flow process of liquid droplets by using the initial velocity of droplet splashing and the angle of the obtained information using computerised fluid dynamics technology. RESULTS: Under different working conditions, the droplet particle splashing velocity, maximum height, and spray angle varied, but the particle trajectory was generally parabolic. The maximum droplet velocity varied between 3.56 and 8.56 m/s, and the splashing height was between 40 and 110 mm. CONCLUSIONS: During risk assessment of an ultrasonic scaler usage, difficulties arise due to the insufficient research on droplet velocity and distribution. This study aims to address this gap by visualising the flow trajectories of droplets generated by ultrasonic scalers. The obtained data will assist in developing more effective interventions based on spatial and temporal distribution of droplets. This provides a new approach for droplet particle research and offers new strategies for public health prevention and control.


Assuntos
Raspagem Dentária , Humanos , Raspagem Dentária/instrumentação , Hidrodinâmica , Processamento de Imagem Assistida por Computador/métodos , Ultrassom/instrumentação , Simulação por Computador
13.
Surg Innov ; 31(2): 173-177, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38182546

RESUMO

PURPOSE: Numerous modifications laparoscopic techniques have mushroomed in recent years. Here we describe a modified technique of extracorporeal ligation of processus vaginalis in children using a hernia crochet needle with a cannula. METHODS: Processus vaginalis repair was carried out on patients diagnosed with inguinal hernia or hydroceles using this novel technique between June 2021 and June 2022. The processus vaginalis was closed extracorporeally using a hernia crochet needle with a cannula. In the presence of patent processus vaginalis, the same procedure would be performed on the contralateral side. The primary outcomes was the safety and efficiency of this modified procedure, and the secondary outcomes was the post operative complications. RESULTS: A total of 212 (165 inguinal hernia and 47 hydroceles) children were corrected by this novel technique. The mean operation time was 27.49 min for unilateral inguinal hernia cases and 36.55 min for bilateral cases. The unilateral hydrocele median operation time was 27.83 min and that for the bilateral cases was 37.30 min. During the mean of 10.92 months of follow-up, there was only a boy subject to a metachronous contralateral occurrence of hernia 10 months after surgery, and no other complications (knot reactions, testicular atrophy, postoperative hydrocele or iatrogenic) have been observed yet. CONCLUSION: This study shown a unique procedure with using a hernia crochet needle with a cannula to be simple, safe, and effective in managing inguinal hernias and hydroceles in the pediatric population.


Assuntos
Hérnia Inguinal , Laparoscopia , Hidrocele Testicular , Masculino , Criança , Humanos , Lactente , Hérnia Inguinal/cirurgia , Cânula , Resultado do Tratamento , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Hidrocele Testicular/cirurgia , Estudos Retrospectivos
14.
Foods ; 12(19)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37835233

RESUMO

Inactivation is a crucial step in the production of postbiotics, with thermal inactivation being the prevailing method employed. Nevertheless, the impact of thermal treatment on bioactivity and chemical composition remains unexplored. The objective of this study was to assess the influence of heating temperature on the antioxidant, anti-inflammatory properties and the chemical composition of ET-22 and BL-99 postbiotics. The findings revealed that subjecting ET-22 and BL-99 to thermal treatment ranging from 70 °C to 121 °C for a duration of 10 min effectively deactivated them, leading to the disruption of cellular structure and release of intracellular contents. The antioxidant and anti-inflammatory activity of ET-22 and BL-99 postbiotics remained unaffected by mild heating temperatures (below 100 °C). However, excessive heating at 121 °C diminished the antioxidant activity of the postbiotic. To further investigate the impact of thermal treatments on chemical composition, non-targeted metabolomics was conducted to analyze the cell-free supernatants derived from ET-22 and BL-99. The results revealed that compared to mild inactivation at temperatures below 100 °C, the excessive temperature of 121 °C significantly altered the chemical profile of the postbiotic. Several bioactive components with antioxidant and anti-inflammatory properties, including zomepirac, flumethasone, 6-hydroxyhexanoic acid, and phenyllactic acid, exhibited a significant reduction in their levels following exposure to a temperature of 121 °C. This decline in their abundance may be associated with a corresponding decrease in their antioxidant and anti-inflammatory activities. The cumulative evidence gathered strongly indicates that heating temperatures exert a discernible influence on the properties of postbiotics, whereby excessive heating leads to the degradation of heat-sensitive active constituents and subsequent diminishment of their biological efficacy.

15.
Medicine (Baltimore) ; 102(34): e34591, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37653819

RESUMO

Filtration surgery (Trabeculectomy) is the main treatment for glaucoma. The scarring of the filtration bleb and obstruction of the outflow of aqueous humor through the filtration channel are the main reasons of the surgery failure. The objective of this study was to determine the clinical efficacy of needle revision of filtration blebs combined with subconjunctival injection of conbercept on the functional bleb formation in glaucoma patients with eye pressure out of control after trabeculectomy. A total of 48 eyes with poor filtration bleb function after trabeculectomy for glaucoma were treated with needle revision of filtration bleb combined with subconjunctival injection of conbercept. After the treatment, the patients were followed up for 3 months during which visual acuity, intraocular pressure, slit lamp and ultrasound biomicroscope examinations were performed. Intraoperative and postoperative complications were recorded. The visual acuity and intraocular pressure were significantly improved after the needle revision of filtration blebs. Among the 48 eyes, 39 eyes still had functional blebs at the end of the follow-up period, and filtration blebs failed in 9 eyes 2 to 8 weeks after the removal of the needle. The survival rate of filtration blebs at 3 months after needle revision was (79.06 ±â€…3.42%), and 81.25% (39/48) of the eyes showed good formation rate of functional bleb at the last follow-up. Three months after needle revision, there was local scar formation in some filtration blebs. Part of the filtration blebs showed mild thickening of the local subconjunctival tissue, and the filtration bleb was slightly raised and diffuse, showing a multi-cavity and thin-walled shape in some blebs. Ultrasound biomicroscopy examination showed relative structural manifestations. Subconjunctival hemorrhage occurred in 43 patients during and after the operation. Low intraocular pressure occurred in 8 patients with the lowest pressure of 5 mm Hg. Choroidal edema was observed in 3 patients. Five patients had intraoperative conjunctival hemorrhage in the anterior chamber, and hyphema occurred. All complications were self-limited and resolved without surgical intervention. Needle revision of filtration bleb combined with anti-VEGF drugs is a safe and effective method for the treatment of filtration bleb dysfunction after surgery of glaucoma.


Assuntos
Glaucoma , Trabeculectomia , Humanos , Trabeculectomia/efeitos adversos , Glaucoma/cirurgia , Túnica Conjuntiva/cirurgia , Hifema
16.
World J Gastrointest Surg ; 15(7): 1317-1330, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37555121

RESUMO

BACKGROUND: The prevention and treatment of Hirschsprung-associated enterocolitis (HAEC) is a serious challenge in pediatric surgery. Exploring the mechanism of HAEC is conducive to the prevention of this disease. AIM: To explore the possible mechanism of glycyrrhizic acid (GA) and its therapeutic effect on HAEC. METHODS: We developed a model of enteritis induced by trinitrobenzenesulfonic acid (TNBS) in zebrafish, and treated it with different concentrations of GA. We analyzed the effect of GA on the phenotype and inflammation of zebrafish. RESULTS: After treatment with TNBS, the area of the intestinal lumen in zebrafish was significantly increased, but the number of goblet cells in the intestinal lumen was significantly reduced, but these did not increase the mortality of zebrafish, indicating that the zebrafish enteritis model was successfully developed. Different concentrations of GA protected zebrafish with enteritis. In particular, high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area, increased the number of goblet cells in the intestinal lumen, and reduced the levels of interleukin (IL)-1ß and IL-8. CONCLUSION: GA significantly reduced the intestinal luminal area, increased the number of intestinal goblet cells, and decreased IL-1ß and IL-8 in zebrafish, and is important for prevention and control of HAEC.

17.
Front Immunol ; 14: 1215745, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520554

RESUMO

Objective: To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis. And to construct prediction models to aid in the prediction and improvement of prognosis. Methods: We searched PubMed, Embase, Web of Science and Cochrane Library for relevant studies from inception to March 29, 2023. After completing literature screening and data extraction, we performed meta-analysis, sensitivity analysis, and subgroup analysis to identify risk factors associated with OS and PFS. Using the pooled hazard ratio value for each risk factor, we constructed prediction models, which were then validated using datasets from 19 centers in Japan and two centers in China, comprising a total of 204 patients. Results: A total of 47 studies, involving a total of 7649 ICI-treated HCC patients, were included in the meta-analysis. After analyzing 18 risk factors, we identified AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number, vascular invasion and combination therapy as predictors for OS prediction model, while AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number and vascular invasion were selected as predictors for PFS model. To validate the models, we scored two independent cohorts of patients using both prediction models. Our models demonstrated good performance in these cohorts. In addition, in the pooled cohort of 204 patients, Our models also showed good performance with area under the curve (AUC) values of 0.712, 0.753, and 0.822 for the OS prediction model at 1-year, 2-year, and 3-year follow-up points, respectively, and AUC values of 0.575, 0.749 and 0.691 for the PFS prediction model Additionally, the calibration curve, decision curve analysis, and Kaplan-Meier curves in the pooled cohort all supported the validity of both models. Conclusion: Based on the meta-analysis, we successfully constructed the OS and PFS prediction models for ICI-treated HCC patients. We also validated the models externally and observed good discrimination and calibration. The model's selected indicators are easily obtainable, making them suitable for further application in clinical practice.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Prognóstico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas
18.
Front Pediatr ; 11: 1182342, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37292375

RESUMO

Anorectal malformation (ARM) and Hirschsprungs disease (HSCR) are frequently associated with other congenital malformations, but rarely with one another. We describe the case of a child with intermediate anorectal malformation who underwent ARM correction. This child experienced recurrent postoperative symptoms, including intestinal obstruction, nutrition intolerance, and weight loss. The child was diagnosed with Hirschsprung's disease by colon barium contrast and pathological findings from a rectal biopsy, and subsequently underwent pull -through procedure after conservative treatment failed. After six months of postoperative follow-up, the patient still experiences occasional episodes of enteritis, but the symptoms are substantially less severe than they were before surgery, and the patient's weight is slowly increasing. We described a case of a child who had ARM combined with HSCR. Although the association between ARM and HSCR is uncommon, severe constipation or enteritis following complete correction of ARM in the absence of anal stricture should prompt consideration for HSCR. Before the second stage of ARM surgery, pay close attention to the barium enema examination, as an abnormal shape may indicate the presence of HSCR.

19.
Front Pediatr ; 11: 1112034, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063672

RESUMO

Background/purpose: Rhubarb peony decoction (RPD) is a formula of traditional Chinese medicine that has been widely used to treat intra-abdominal inflammatory diseases. To investigate the therapeutic efficacy of RPD in pediatric periappendiceal abscess, patients who received intravenous antibiotics alone were compared with those treated with intravenous antibiotics combined with RPD. Methods: A retrospective review of children with periappendiceal abscess who received conservative treatment in our hospital between January 2013 and April 2022 was performed. The patients were divided into an intravenous antibiotic group (the control group) and an intravenous antibiotic combined with RPD group (the intervention group). Interval appendectomy (IA) was generally performed 10-12 weeks after conservative treatment. The primary outcome was the cure rate of conservative treatment, while the secondary outcomes included the recurrence rate, days of total intravenous antibiotic use, length of hospital stay (LOS), postoperative complications, and liver injury caused by RPD. Results: A total of 142 patients (77 girls and 65 boys) were included, 52 in the control group and 90 in the intervention group. The two groups were similar in demographic data and clinical characteristics (P > 0.05). The mean total course of RPD in the intervention group was 11.82 days. The intervention group had a significantly higher cure rate than the control group (93.33% vs. 80.77%, P = 0.029), and the length of total intravenous antibiotic use (P = 0.150), LOS (P = 0.077), recurrence rate (9.52% vs. 4.76%, P = 0.439), as well as the operation time (P = 0.101), LOS (P = 0.572), and postoperative complications (P = 0.549) were not significantly different between the two groups when the patients received IA. No patient had a liver injury caused by RPD during the treatment. Conclusion: Intravenous antibiotics combined with RPD demonstrated high effectiveness and safety for treating pediatric periappendiceal abscess.

20.
BMC Med Inform Decis Mak ; 23(1): 33, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788560

RESUMO

BACKGROUND: Semantic segmentation of brain tumors plays a critical role in clinical treatment, especially for three-dimensional (3D) magnetic resonance imaging, which is often used in clinical practice. Automatic segmentation of the 3D structure of brain tumors can quickly help physicians understand the properties of tumors, such as the shape and size, thus improving the efficiency of preoperative planning and the odds of successful surgery. In past decades, 3D convolutional neural networks (CNNs) have dominated automatic segmentation methods for 3D medical images, and these network structures have achieved good results. However, to reduce the number of neural network parameters, practitioners ensure that the size of convolutional kernels in 3D convolutional operations generally does not exceed [Formula: see text], which also leads to CNNs showing limitations in learning long-distance dependent information. Vision Transformer (ViT) is very good at learning long-distance dependent information in images, but it suffers from the problems of many parameters. What's worse, the ViT cannot learn local dependency information in the previous layers under the condition of insufficient data. However, in the image segmentation task, being able to learn this local dependency information in the previous layers makes a big impact on the performance of the model. METHODS: This paper proposes the Swin Unet3D model, which represents voxel segmentation on medical images as a sequence-to-sequence prediction. The feature extraction sub-module in the model is designed as a parallel structure of Convolution and ViT so that all layers of the model are able to adequately learn both global and local dependency information in the image. RESULTS: On the validation dataset of Brats2021, our proposed model achieves dice coefficients of 0.840, 0.874, and 0.911 on the ET channel, TC channel, and WT channel, respectively. On the validation dataset of Brats2018, our model achieves dice coefficients of 0.716, 0.761, and 0.874 on the corresponding channels, respectively. CONCLUSION: We propose a new segmentation model that combines the advantages of Vision Transformer and Convolution and achieves a better balance between the number of model parameters and segmentation accuracy. The code can be found at https://github.com/1152545264/SwinUnet3D .


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Humanos , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Imageamento Tridimensional/métodos , Redes Neurais de Computação , Algoritmos
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