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1.
PLoS Biol ; 21(6): e3002131, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37279234

RESUMO

Orcinol glucoside (OG), mainly found in the rhizome of the traditional Chinese herb Curculigo orchioides Gaertn, is noted for its antidepressant effects. In this study, an efficient screening pipeline was established for identifying the highly active orcinol synthase (ORS) and UDP-dependent glycosyltransferase (UGT) involved in the biosynthesis of OG by combining transcriptome analysis, structure-based virtual screening, and in vitro enzyme activity assays. By enhancing the downstream pathway, metabolic engineering and fermentation optimization, the OG production in Yarrowia lipolytica was improved 100-fold, resulting in a final yield of 43.46 g/L (0.84 g/g DCW), which is almost 6,400-fold higher than the extraction yield from C. orchioides roots. This study provides a reference for rapid identification of functional genes and high-yield production of natural products.


Assuntos
Glucosídeos , Yarrowia , Glucosídeos/metabolismo , Yarrowia/genética , Engenharia Metabólica/métodos , Fermentação
2.
FASEB J ; 38(18): e70064, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39295162

RESUMO

12-hydroxyeicosatetraenoic acid (12-HETE), a major metabolite of arachidonic acid, is converted by 12/15-lipoxygenase and implicated in diabetic retinopathy (DR). Our previous study demonstrated a positive correlation between 12-HETE and the prevalence of DR. However, reasons for the increased production of 12-HETE are unclear, and the underlying mechanisms through which 12-HETE promotes DR are unknown. This study aimed to elucidate the correlation between 12-HETE and DR onset, investigate potential mechanisms through which 12-HETE promotes DR, and seek explanations for the increased production of 12-HETE in diabetes. We conducted a prospective cohort study, which revealed that higher serum 12-HETE levels could induce DR. Additionally, G protein-coupled receptor 31 (GPR31), a high-affinity receptor for 12-HETE, was expressed in human retinal microvascular endothelial cells (HRMECs). 12-HETE/GPR31-mediated HRMEC inflammation occurred via the p38 MAPK pathway. 12-HETE levels were significantly higher in the retina of mice with high-fat diet (HFD)- and streptozotocin (STZ)-induced diabetes than in those with only STZ-induced diabetes and healthy controls. They were positively correlated with the levels of inflammatory cytokines in the retina, indicating that HFD could induce increased 12-HETE synthesis in patients with diabetes in addition to hyperglycemia. Conclusively, 12-HETE is a potential risk factor for DR. The 12-HETE/GPR31 axis plays a crucial role in HRMEC dysfunction and could be a novel target for DR prevention and control. Nevertheless, further research is warranted to provide comprehensive insights into the complex underlying mechanisms of 12-HETE in DR.


Assuntos
Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico , Diabetes Mellitus Experimental , Retinopatia Diabética , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas G , Retinopatia Diabética/metabolismo , Retinopatia Diabética/etiologia , Retinopatia Diabética/patologia , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Humanos , Animais , Receptores Acoplados a Proteínas G/metabolismo , Camundongos , Masculino , Diabetes Mellitus Experimental/metabolismo , Feminino , Células Endoteliais/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Células Cultivadas
3.
Mol Med ; 30(1): 105, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030525

RESUMO

Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.


Assuntos
Microbioma Gastrointestinal , Neoplasias , Probióticos , Radioterapia , Humanos , Microbioma Gastrointestinal/efeitos da radiação , Neoplasias/radioterapia , Neoplasias/microbiologia , Neoplasias/imunologia , Neoplasias/terapia , Probióticos/uso terapêutico , Radioterapia/efeitos adversos , Radioterapia/métodos , Animais , Microbiota/efeitos da radiação , Lesões por Radiação/microbiologia , Lesões por Radiação/terapia , Lesões por Radiação/etiologia , Resultado do Tratamento
4.
BMC Microbiol ; 24(1): 19, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200418

RESUMO

BACKGROUND: This study investigates the variations in microbiome abundance and diversity on the ocular surfaces of diabetic patients suffering from dry eye within a community setting. The goal is to offer theoretical insights for the community-level prevention and treatment of dry eye in diabetic cohorts. METHODS: Dry eye screening was performed in the Shanghai Cohort Study of Diabetic Eye Disease (SCODE) from July 15, 2021, to August 15, 2021, in the Xingjing community; this study included both a population with diabetes and a normal population. The population with diabetes included a dry eye group (DM-DE, n = 40) and a non-dry eye group (DM-NoDE, n = 39). The normal population included a dry eye group (NoDM-DE, n = 40) and a control group (control, n = 39). High-throughput sequencing of the 16 S rRNA V3-V4 region was performed on conjunctival swab from both eyes of each subject, and the composition of microbiome on the ocular surface of each group was analyzed. RESULTS: Significant statistical differences were observed in both α and ß diversity of the ocular surface microbiome among the diabetic dry eye, diabetic non-dry eye, non-diabetic dry eye, and normal control groups (P < 0.05). CONCLUSIONS: The study revealed distinct microecological compositions on the ocular surfaces between the diabetic dry eye group and other studied groups. Firmicutes and Anoxybacillus were unique bacterial phyla and genera in the dry eye with DM group, while Actinobacteria and Corynebacterium were unique bacterial phyla and genera in the normal control group.


Assuntos
Diabetes Mellitus , Síndromes do Olho Seco , Microbiota , Humanos , Estudos de Coortes , China
5.
Biomed Eng Online ; 23(1): 32, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475784

RESUMO

PURPOSE: This study aimed to investigate the imaging repeatability of self-service fundus photography compared to traditional fundus photography performed by experienced operators. DESIGN: Prospective cross-sectional study. METHODS: In a community-based eye diseases screening site, we recruited 65 eyes (65 participants) from the resident population of Shanghai, China. All participants were devoid of cataract or any other conditions that could potentially compromise the quality of fundus imaging. Participants were categorized into fully self-service fundus photography or traditional fundus photography group. Image quantitative analysis software was used to extract clinically relevant indicators from the fundus images. Finally, a statistical analysis was performed to depict the imaging repeatability of fully self-service fundus photography. RESULTS: There was no statistical difference in the absolute differences, or the extents of variation of the indicators between the two groups. The extents of variation of all the measurement indicators, with the exception of the optic cup area, were below 10% in both groups. The Bland-Altman plots and multivariate analysis results were consistent with results mentioned above. CONCLUSIONS: The image repeatability of fully self-service fundus photography is comparable to that of traditional fundus photography performed by professionals, demonstrating promise in large-scale eye disease screening programs.


Assuntos
Serviços de Saúde Comunitária , Glaucoma , Humanos , Estudos Transversais , Estudos Prospectivos , China , Fotografação/métodos , Fundo de Olho
6.
Appl Microbiol Biotechnol ; 108(1): 497, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39466432

RESUMO

The gut microbiota has emerged as an independent risk factor for diabetes and its complications. This research aimed to delve into the intricate relationship between the gut microbiome and diabetic retinopathy (DR) through a dual approach of cross-sectional and prospective cohort studies. In our cross-sectional study cross-sectional investigation involving ninety-nine individuals with diabetes, distinct microbial signatures associated with DR were identified. Specifically, gut microbiome profiling revealed decreased levels of Butyricicoccus and Ruminococcus torques group, alongside upregulated methanogenesis pathways among DR patients. These individuals concurrently exhibited lower concentrations of short-chain fatty acids in their plasma. Leveraging machine learning models, including random forest classifiers, we constructed a panel of microbial genera and genes that robustly differentiated DR cases. Importantly, these genera also demonstrated significant correlations with dietary patterns and the molecular profiles of peripheral blood mononuclear cells. Building upon these findings, our prospective cohort study followed 62 diabetes patients over a 2-year period to assess the predictive value of these microbial markers. The results underlined the panel's efficacy in predicting DR incidence. By stratifying patients based on the predictive genera and metabolites identified in the cross-sectional phase, we established significant associations between reduced levels of Butyricicoccus, plasma acetate, and increased susceptibility to DR. This investigation not only deepens our understanding of how gut microbiota influences DR but also underscores the potential of microbial markers as early indicators of disease risk. These insights hold promise for developing targeted interventions aimed at mitigating the impact of diabetic complications. KEY POINTS: • Microbial signatures are differed in diabetic patients with and without retinopathy • DR-related taxa are linked to dietary habits and transcriptomic profiles • Lower abundances of Butyricicoccus and acetate were prospectively associated with DR.


Assuntos
Retinopatia Diabética , Microbioma Gastrointestinal , Humanos , Estudos Transversais , Masculino , Retinopatia Diabética/microbiologia , Retinopatia Diabética/sangue , Pessoa de Meia-Idade , Estudos Longitudinais , Estudos Prospectivos , Feminino , Ácidos Graxos Voláteis/sangue , Ácidos Graxos Voláteis/metabolismo , Idoso , Ruminococcus/genética , Ruminococcus/isolamento & purificação , Clostridiales/genética , Acetatos/metabolismo , Acetatos/sangue , Adulto , Diabetes Mellitus/microbiologia
7.
Lipids Health Dis ; 23(1): 75, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468242

RESUMO

BACKGROUND: The association between remnant cholesterol (RC) and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) remains unclear. Morphological changes in retinal vessels have been reported to predict vascular complications of diabetes, including DR. METHODS: This cross-sectional study included 6535 individuals with T2DM. The RC value was calculated using the recognized formula. The retinal vascular parameters were measured using fundus photography. The independent relationship between RC and DR was analyzed using binary logistic regression models. Multiple linear regression and subgroup analyses were employed to investigate the link between RC and vascular parameters, including the retinal arteriolar diameter (CRAE), venular diameter (CRVE), and fractal dimension (Df). Mediation analysis was performed to assess whether the vascular morphology could explain the association between RC and DR. RESULTS: RC was independently associated with DR in patients with a longer duration of T2DM (> 7 years). Patients with the highest quartile RC levels had larger CRAE (5.559 [4.093, 7.025] µm), CRVE (7.620 [5.298, 9.941] µm) and Df (0.013 [0.009, 0.017]) compared with patients with the lowest quartile RC levels. Results were robust across different subgroups. The association between RC and DR was mediated by CRVE (0.020 ± 0.005; 95% confidence interval: 0.012-0.032). CONCLUSIONS: RC may be a risk factor for DR among those who have had T2DM for a longer period of time. Higher RC levels were correlated with wider retinal arterioles and venules as well as higher Df, and it may contribute to DR through the dilation of retinal venules.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/complicações , Estudos Transversais , Fatores de Risco , Vasos Retinianos/diagnóstico por imagem , Colesterol
8.
BMC Pediatr ; 24(1): 203, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519924

RESUMO

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.


Assuntos
Histiocitose de Células de Langerhans , Hipoalbuminemia , Criança , Humanos , Hipoalbuminemia/complicações , Hipoalbuminemia/patologia , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/patologia , Trato Gastrointestinal/patologia , Biópsia , Diarreia/complicações
9.
J Med Internet Res ; 26: e45545, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630535

RESUMO

BACKGROUND: Fundus photography is the most important examination in eye disease screening. A facilitated self-service eye screening pattern based on the fully automatic fundus camera was developed in 2022 in Shanghai, China; it may help solve the problem of insufficient human resources in primary health care institutions. However, the service quality and residents' preference for this new pattern are unclear. OBJECTIVE: This study aimed to compare the service quality and residents' preferences between facilitated self-service eye screening and traditional manual screening and to explore the relationships between the screening service's quality and residents' preferences. METHODS: We conducted a cross-sectional study in Shanghai, China. Residents who underwent facilitated self-service fundus disease screening at one of the screening sites were assigned to the exposure group; those who were screened with a traditional fundus camera operated by an optometrist at an adjacent site comprised the control group. The primary outcome was the screening service quality, including effectiveness (image quality and screening efficiency), physiological discomfort, safety, convenience, and trustworthiness. The secondary outcome was the participants' preferences. Differences in service quality and the participants' preferences between the 2 groups were compared using chi-square tests separately. Subgroup analyses for exploring the relationships between the screening service's quality and residents' preference were conducted using generalized logit models. RESULTS: A total of 358 residents enrolled; among them, 176 (49.16%) were included in the exposure group and the remaining 182 (50.84%) in the control group. Residents' basic characteristics were balanced between the 2 groups. There was no significant difference in service quality between the 2 groups (image quality pass rate: P=.79; average screening time: P=.57; no physiological discomfort rate: P=.92; safety rate: P=.78; convenience rate: P=.95; trustworthiness rate: P=.20). However, the proportion of participants who were willing to use the same technology for their next screening was significantly lower in the exposure group than in the control group (P<.001). Subgroup analyses suggest that distrust in the facilitated self-service eye screening might increase the probability of refusal to undergo screening (P=.02). CONCLUSIONS: This study confirms that the facilitated self-service fundus disease screening pattern could achieve good service quality. However, it was difficult to reverse residents' preferences for manual screening in a short period, especially when the original manual service was already excellent. Therefore, the digital transformation of health care must be cautious. We suggest that attention be paid to the residents' individual needs. More efficient man-machine collaboration and personalized health management solutions based on large language models are both needed.


Assuntos
Idioma , Humanos , Estudos Transversais , China , Modelos Logísticos
10.
Molecules ; 29(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38675519

RESUMO

The massive amount of water-soluble urea used leads to nutrient loss and environmental pollution in both water and soil. The aim of this study was to develop a novel lignin-based slow-release envelope material that has essential nitrogen and sulfur elements for plants. After the amination reaction with a hydrolysate of yak hair keratin, the coating formulation was obtained by adding different loadings (2, 5, 8, 14 wt%) of aminated lignin (AL) to 5% polyvinyl alcohol (PVA) solution. These formulations were cast into films and characterized for their structure, thermal stability, and mechanical and physicochemical properties. The results showed that the PVA-AL (8%) formulation had good physical and chemical properties in terms of water absorption and mechanical properties, and it showed good degradation in soil with 51% weight loss after 45 days. It is suitable for use as a coating material for fertilizers. Through high-pressure spraying technology, enveloped urea particles with a PVA-AL (8%) solution were obtained, which showed good morphology and slow-release performance. Compared with urea, the highest urea release was only 96.4% after 30 days, conforming to Higuchi model, Ritger-Peppas model, and second-order dynamic model. The continuous nitrogen supply of PVA-AL coated urea to Brassica napus was verified by potting experiments. Therefore, the lignin-based composite can be used as a coating material to produce a new slow-release nitrogen fertilizer for sustainable crop production.


Assuntos
Lignina , Álcool de Polivinil , Ureia , Lignina/química , Álcool de Polivinil/química , Ureia/química , Preparações de Ação Retardada/química , Fertilizantes , Polímeros/química
11.
Actas Esp Psiquiatr ; 52(5): 693-704, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39403905

RESUMO

BACKGROUND: Post-stroke depression (PSD) is a common complication, occurring in approximately one-third of these patients. The neurological symptoms of PSD affect patients' daily life and subsequent recovery. Analyzing the pathogenesis of post-stroke depression from a psychological perspective, it was found that PSD patients often feel despair and anxiety, and it is crucial to explore non-pharmacological ways to improve post-stroke depressive symptoms. A combination of exercise and rich environmental stimulation (RES) has been found effective in improving post-stroke depressive symptoms. Therefore, this study aimed to explore the effects of exercise and rich environmental stimulation on PSD in rats and their potential underlying mechanisms and to provide a theoretical basis for managing PSD. METHODS: The PSD rat model was constructed, and the depression-like behaviors of rats in each group were evaluated using the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Moreover, changes in the morphological behavior of rat hippocampus were observed using hematoxylin-eosin (HE) staining and Nissl staining. The expression levels of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hippocampus tissues were assessed using enzyme linked immunosorbent assay (ELISA), and the levels of tryptophan-related proteins were determined employing western blot analysis. Additionally, a kynurenine-3-monooxygenase (KMO) inhibitor was administered to the combined stimulation group, and the levels of tryptophan (TRP), 5-HT, kynurenine (KYN), 3-hydroxy-kynurenine (3-HK), and quinolinic acid (QA) were evaluated using liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS). RESULTS: Treadmill exercise combined with rich environmental stimulation significantly reduced the immobility time in the FST (p < 0.01), increased the exploratory behavior in the OFT (p < 0.05), and increased the sucrose water consumption in the SPT (p < 0.01), indicating that the depression-like behavior was improved. Treadmill exercise combined with rich environmental stimulation also improved the shape of the damaged hippocampus and increased the number of neurons in the hippocampus. Additionally, treadmill exercise combined with rich environmental stimulation significantly increased the levels of 5-HT and NE in hippocampus tissues (p < 0.01) and decreased KMO protein level (p < 0.01). In the KMO inhibitor group, the neural function was efficiently restored, the levels of 3-HK, QA, and KMO in the hippocampus were substantially reduced (p < 0.01), and the expression level of 5-HT was increased (p < 0.01). CONCLUSIONS: Exercise stimulation combined with enriched environmental stimuli alleviates post-stroke depression in rats, and the underlying mechanisms may be related to TRP/KYN/3-HK/QA excitotoxicity pathways and increased 5-hydroxytryptamine levels.


Assuntos
Depressão , Modelos Animais de Doenças , Condicionamento Físico Animal , Ratos Sprague-Dawley , Acidente Vascular Cerebral , Animais , Depressão/terapia , Depressão/etiologia , Ratos , Masculino , Acidente Vascular Cerebral/complicações , Hipocampo/metabolismo , Meio Ambiente , Serotonina/metabolismo
12.
Pak J Med Sci ; 40(6): 1294-1299, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952502

RESUMO

Objectives: Mixed-phenotype acute leukemia (MPAL) is rare in the clinic, accounting for approximately 2%-5% of acute leukemia cases. Methods: In this study the cohort included 126 patients, of which 125 cases were from re-examined published data and current patients from Shenzhen Longhua District Central Hospital, carrying an ETV6-ABL1 rearrangement from April 15, 2020 to December 19, 2020. The ETS variant transcription factor 6-Abelson proto-oncogene 1 (ETV6-ABL1) fusion gene is mainly seen in malignant hematological diseases such as acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myeloproliferative neoplasms (MPNs). Positivity of both MPAL and ETV6-ABL1 suggest a poor prognosis. This is the first report of B lymphocytic/myeloid mixed-phenotype acute leukemia with ETV6-ABL1 fusion gene positivity. Complete remission was achieved with chemotherapy for lymphoid and myeloid leukemia and targeted therapy with tyrosine kinase inhibitors (TKIs). Results: The level of ETV6-ABL1/ABL decreased from 23.056% to 11.165%. After consolidation chemotherapy, the patient underwent allogeneic hematopoietic stem cell transplantation but died due to intestinal rejection. There are 126 cases of ETV6-ABL1 fusion gene transcript expression in numerous hematologic malignancies reported to date, including 48 cases of ALL, 12 of AML, and 65 of MPN. Eosinophilia is a common characteristic, especially in MPN patients. Conclusion: Survival analysis suggests that the survival time of ALL and MPN patients receiving TKI treatment is better than that of patients not receiving this treatment. Dasatinib or nilotinib, especially the former, is more effective than imatinib for MPN.

13.
FASEB J ; 36(3): e22194, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35170814

RESUMO

The leiomodin1 (LMOD1) gene, encoding a potent actin nucleator, was recently reported as a potential pathogenic gene of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS, OMIM 619362). However, only a single patient has been reported to have LMOD1 mutations, and the underlying pathogenic mechanism remains unknown. Here, we described a male infant with LMOD1 mutations presenting typical symptoms of pediatric intestinal pseudo-obstruction (PIPO) but without megacystis and microcolon. Two compound heterozygous missense variants (c.1106C>T, p.T369M; c.1262G>A, p.R421H) were identified, both affecting highly conserved amino acid residues within the second actin-binding site (ABS2) domain of LMOD1. Expression analysis showed that both variants resulted in significantly reduced protein amounts, especially for p.T369M, which was almost undetectable. The reduction was only partially rescued by the proteasome inhibitor MG-132, indicating that there might be proteasome-independent pathways involved in the degradation of the mutant proteins. Molecular modeling showed that variant p.T369M impaired the local protein conformation of the ABS2 domain, while variant p.R421H directly impaired the intermolecular interaction between ABS2 and actin. Accordingly, both variants significantly damaged LMOD1-mediated actin nucleation. These findings provide further human genetic evidence supporting LMOD1 as a pathogenic gene underlying visceral myopathy including PIPO and MMIHS, strengthen the critical role of ABS2 domain in LMOD1-mediated actin nucleation, and moreover, reveal an unrecognized role of ABS2 in protein stability.


Assuntos
Actinas/metabolismo , Autoantígenos/genética , Proteínas do Citoesqueleto/genética , Pseudo-Obstrução Intestinal/genética , Mutação com Perda de Função , Autoantígenos/química , Autoantígenos/metabolismo , Sítios de Ligação , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/metabolismo , Células HeLa , Humanos , Lactente , Pseudo-Obstrução Intestinal/metabolismo , Pseudo-Obstrução Intestinal/patologia , Masculino , Simulação de Acoplamento Molecular , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Estabilidade Proteica
14.
Cancer Control ; 30: 10732748231197511, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37673428

RESUMO

OBJECTIVE: We aimed to retrospectively investigate whether the neutrophil to lymphocyte ratio (NLR) and the monocyte to lymphocyte ratio (MLR) can predict the prognosis of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib or sorafenib. METHODS: We retrospectively identified 210 patients with mRCC treated with sunitinib or sorafenib from 2007 to 2017 at Fudan University- and Hexi University-affiliated hospitals. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Multivariate regression analysis was used to evaluate predictors of PFS and OS. RESULTS: Low NLR (<2.85) and MLR (<.30) were strongly associated with increased PFS and OS. Multivariable analyses verified that the NLR and MLR were both independent prognostic factors. Additionally, the NLR was negatively correlated with CD8+ and CD4+ T-cell infiltration in tumors. CONCLUSION: In patients with mRCC treated with sunitinib and sorafenib, an NLR <2.85 and MLR <.30 was associated with superior PFS and OS, which may be related to the reduced lymphocytic infiltration of tumors.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Sunitinibe/uso terapêutico , Sorafenibe/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Estudos Retrospectivos , Biomarcadores , Prognóstico , Linfócitos/patologia
15.
BMC Pediatr ; 23(1): 126, 2023 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-36934232

RESUMO

BACKGROUND: In a cohort of hospitalized children with congenital heart disease (CHD), a new digital pediatric malnutrition screening tool as a mobile application was validated, and its effectiveness and clinical value were determined as a prospective study. METHODS AND RESULTS: Children with CHD (n = 1125) were screened for malnutrition risk. The incidence of risk and the differences among various age groups and types of CHD were characterized. The optimal threshold for the tool to determine if there is a risk of malnutrition is score 2, while the Youden index was 79.1%, and the sensitivity and specificity were 91.2% and 87.9%, respectively. Based on such criterion, 351 children were at risk of malnutrition accounting for 31.20% of the total. Compared with the non-malnutritional risk group, the median age for the group at risk for malnutrition was younger (8.641 months [4.8, 23.1] vs. 31.589 months [12.4, 54.3], P < 0.01), and the length of stay was longer (12.000 [8.0, 17.0] vs. (8.420 [5.0, 12.0], P < 0.01]. There were significant differences in malnutrition risk among different age groups (χ2 = 144.933, P < 0.01), and children under one year of age exhibited the highest risk for malnutrition and more extended hospital stay (H = 78.085, P < 0.01). The risk of malnutrition among children with cyanotic CHD was higher than in those with non-cyanotic CHD (χ2 = 104.384, P < 0.01). CONCLUSIONS: The new digital pediatric malnutrition screening tool showed high sensitivity and specificity in children with CHD. The tool indicated that the malnutrition risk for young children and children with cyanotic or Bethesda moderate and complex CHD was higher, and the hospitalization time was longer than in the non-risk group. The tool provides a rational approach to targeted nutrition intervention and support and may improve clinical outcomes.


Assuntos
Cardiopatias Congênitas , Desnutrição , Criança , Humanos , Lactente , Pré-Escolar , Criança Hospitalizada , Estudos Prospectivos , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Hospitalização , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Estado Nutricional
16.
Pediatr Radiol ; 53(7): 1260-1269, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35864243

RESUMO

Pulmonary embolism (PE) is a potentially life-threatening condition that requires immediate medical intervention. Although PE was previously thought to occur infrequently in the pediatric population, recent studies have found a higher-than-expected prevalence of PE in the pediatric population of up to 15.5%. The imaging modality of choice for detecting PE in the pediatric population is multi-detector CT angiography, although MRI is assuming a growing and more important role as a potential alternative modality. Given the recent advances in both computed tomography pulmonary angiography (CTPA) and MRI techniques, a growing population of pediatric patients with complex comorbidities (such as children with a history of surgeries for congenital heart disease repair), and the recent waves of coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C), which are associated with increased risk of PE, there is new and increased need for an up-to-date review of practical CT and MRI protocols for PE evaluation in children. This article provides guidance for up-to-date CT and MR imaging techniques, reviews key recent studies on the imaging of pediatric PE, and discusses relevant pediatric PE imaging pearls and pitfalls, in hopes of providing readers with up-to-date and accurate practice for imaging evaluation of PE in children.


Assuntos
COVID-19 , Embolia Pulmonar , Humanos , Criança , Tomografia Computadorizada por Raios X/métodos , Embolia Pulmonar/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
17.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37806347

RESUMO

INTRODUCTION: As the population ages, surgeons are growing frequently faced with hard choices among a vast array of treatment options for the elderly. This study was to investigate safety and efficacy of resection in elderly patients with perihilar cholangiocarcinoma (PHCC). PATIENTS AND METHODS: Literature reading and meta-analysis unveiled that elderly PHCC patients held a higher risk of death within 90 days after hepatectomy relative to younger patients, but their 5-year overall survival and disease-free survival were comparable. Among PHCC patients who underwent hepatectomy, the proportion of elderly patients with tumor classification Bismuth I-II and tumor stage pStage 1-3 was significantly higher than that of younger patients. RESULTS: Curative resection R0 was more common in elderly patients than younger patients, but the difference was not statistically significant. Because of more comorbidities and less physiological reserve of elderly patients, they seemed to suffer more postoperative complications. CONCLUSION: Considering improved life expectancy, it is crucial to treat elderly PHCC patients appropriately and attempts should be made to radical surgery based on comorbidities and functional status.

18.
BMC Ophthalmol ; 22(1): 460, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36451130

RESUMO

AIM: Caffeinated beverages are very popular across populations and cultures, but quantitative evidence of the acute effects of moderate coffee doses on retinal perfusion is sparse and contradicting. Thus, the aim of this randomized, cross-over and parallel-group design study was to investigate whether moderate consumption of coffee alters macular retinal capillary perfusion in young healthy individuals. METHODS: Twenty-seven young healthy individuals were recruited for this study. Acute changes in retinal microvasculature were assessed using spectral-domain optical coherence tomography angiography (SD-OCTA) at baseline, 0.5 h, and 2 h after intake of coffee, or water. Meanwhile, cerebral blood flow (CBF) and retina-choroid blood flow were evaluated in a parallel-group design (4 participants each in coffee or water group) using magnetic resonance imaging (MRI) with pseudo-continuous arterial spin labeling sequences. RESULTS: Two hours after coffee intake, blood caffeine concentration increased from 0 to 5.05 ± 1.36 µg/mL. Coffee caused a significant decrease in retinal vessel diameter index (VDI) (19.05 ± 0.24 versus [vs] 19.13 ± 0.26; p < 0.001) and CBF in the frontal lobe (77.47 ± 15.21 mL/100 mL/min vs. 84.13 ± 15.55 mL/100 mL/min; p < 0.05) 2 h after intake. However, it significantly increased retina-choroid blood flow after 0.5 and 2 h (163.18 ± 61.07 mL/100 mL/min vs. 132.68 ± 70.47 mL/100 mL/min, p < 0.001, and 161.21 ± 47.95 vs. 132.68 ± 70.47; p < 0.001, respectively). CONCLUSION: This is the first study to demonstrate the acute effects of daily dose coffee consumption on retinal capillary perfusion using SD-OCTA combinate with blood flow MRI. The findings imply that although moderate coffee intake caused a significant increase in retina-choroid blood flow, there was a significant acute decrease both in macular retinal capillary perfusion and CBF.


Assuntos
Café , Veias , Humanos , Perfusão , Retina/diagnóstico por imagem , Nível de Saúde
19.
Ophthalmic Res ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36382640

RESUMO

INTRODUCTION: We aimed to detect early retinal microcirculation changes in prediabetic patients and investigate their correlation with clinical examinations. METHODS: Forty-seven prediabetic individuals, 29 controls, and 81 type 2 diabetic mellitus (T2DM) patients were enrolled in this study. A review of clinical data and spectral-domain optical coherence tomography angiography (SD-OCTA) parameters of macular vessel diameter (VD), foveal avascular zone (FAZ), and macular vessel area density (VAD) was performed. RESULTS: Levels of low-density lipoprotein cholesterol and triglycerides in prediabetes and T2DM groups were significantly higher than those in the control group. Urine microalbumin-to-creatinine ratio (ACR) was mildly and moderately increased in the prediabetes and T2DM groups, respectively. Estimated glomerular filtration rate of the three groups were within the normal range. SD-OCTA showed that VAD in the superficial macular area was decreased in the prediabetes group compared to the control group (p=0.01). The FAZ size, particularly in the deep layer, was expanded in the prediabetes group. In the deep retinal layer of the macular area, VD and FAZ size in the prediabetes group were larger than those in the control group. In the prediabetes group, the axial length was significantly correlated with macular VD and FAZ size (p<0.05), and ACR was correlated with FAZ size (p<0.05). Age had a negative correlation with VAD (p<0.01). ACR had a positive correlation with FAZ size (p<0.05). CONCLUSIONS: Enlargement and irregularity of the FAZ area, deep capillary dilation, and decrease in VAD occur in the retina of prediabetes patients with mild kidney function impairment.

20.
BMC Health Serv Res ; 22(1): 160, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35130901

RESUMO

BACKGROUND: The success of telescreening and the management of diabetic retinopathy (DR) in communities depends on stakeholder satisfaction, including both individuals with diabetes and community health center (CHC) staff. In this study, we investigated the satisfaction of both individuals with vision-threatening DR (VTDR) and CHC staff within the Shanghai Eye Disease Study (SEDS) comprehensive system for managing diabetic eye diseases at the primary care level. METHODS: The cross-sectional survey of patients receiving the service included 3,817 respondents with VTDR and focused on their satisfaction with the SEDS system, including the telescreening process, speed of feedback, interpretation of results, increased awareness of related diseases, and eye care services. The survey of the providers included 234 CHC staff respondents and focused on their satisfaction and the main barriers encountered during the implementation of the system. Sociodemographic characteristics and perceived barriers related to satisfaction were identified by conducting univariate and multivariate logistic regression analyses. RESULTS: The overall satisfaction of service recipients was 96.0%, and 75.8% of them were willing to undergo future telescreening for DR. The convenience of telescreening, organization of telescreening, and improvement in related disease awareness significantly correlated with satisfaction. Only 48.3% of the providers were satisfied with the SEDS system. The most frequently mentioned barriers to the development of the system were the inadequate levels of staffing (particularly technical staff), insufficient funding, and incomplete information transmission systems. CONCLUSIONS: Disparities between high patient satisfaction and low provider satisfaction with the SEDS system were mainly related to the current weak level of ophthalmic expertise in the CHCs and the low awareness of screening for diabetic eye diseases among both patients and providers.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , China , Centros Comunitários de Saúde , Estudos Transversais , Retinopatia Diabética/terapia , Humanos , Programas de Rastreamento
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