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1.
Int J Rheum Dis ; 27(7): e15255, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38982881

RESUMO

BACKGROUND: The Oxidative Balance Score (OBS) is a systematic tool to assess the effects of diet and lifestyle in relation to oxidative stress. The association between OBS and gout has not been reported previously. We conducted a cross-sectional study to investigate the complex association between OBS and gout in US adults. METHODS: In all, 10 492 participants were included in this study. The exposure variable was OBS, which was scored by 16 dietary and four lifestyle factors. Multivariate logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were used to analyze the association between OBS and gout. RESULTS: Compared with the lowest OBS quartile group (Q1), the multivariate corrected odds ratio (OR) (95% confidence interval [C]) for the highest quartile of OBS (Q4) was 0.72 (0.52-1.00) (p = .13 for trend); furthermore, the RCS showed a negative linear relationship between OBS and gout (p-nonlinear = .606). CONCLUSION: In conclusion, the risk of gout is higher with high OBS. The prevalence of gout decreased with higher OBS. Diabetes may alter this negative correlation.


Assuntos
Gota , Inquéritos Nutricionais , Estresse Oxidativo , Humanos , Gota/epidemiologia , Gota/diagnóstico , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia , Adulto , Prevalência , Estilo de Vida , Medição de Risco , Dieta/efeitos adversos , Idoso
2.
J Immunother Cancer ; 12(6)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886114

RESUMO

BACKGROUND: Epstein-Barr virus (EBV) is a double-stranded DNA oncogenic virus. Several types of solid tumors, such as nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and lymphoepithelioma-like carcinoma of the lung, have been linked to EBV infection. Currently, several TCR-T-cell therapies for EBV-associated tumors are in clinical trials, but due to the suppressive immune microenvironment of solid tumors, the clinical application of TCR-T-cell therapy for EBV-associated solid tumors is limited. Figuring out the mechanism by which EBV participates in the formation of the tumor immunosuppressive microenvironment will help T cells or TCR-T cells break through the limitation and exert stronger antitumor potential. METHODS: Flow cytometry was used for analyzing macrophage differentiation phenotypes induced by EBV-infected and EBV-uninfected tumors, as well as the function of T cells co-cultured with these macrophages. Xenograft model in mice was used to explore the effects of M2 macrophages, TCR-T cells, and matrix metalloprotein 9 (MMP9) inhibitors on the growth of EBV-infected tumors. RESULTS: EBV-positive tumors exhibited an exhaustion profile of T cells, despite the presence of a large T-cell infiltration. EBV-infected tumors recruited a large number of mononuclear macrophages with CCL5 and induced CD163+M2 macrophages polarization through the secretion of CSF1 and the promotion of autocrine IL10 production by mononuclear macrophages. Massive secretion of MMP9 by this group of CD163+M2 macrophages induced by EBV infection was an important factor contributing to T-cell exhaustion and TCR-T-cell therapy resistance in EBV-positive tumors, and the use of MMP9 inhibitors improved the function of T cells cocultured with M2 macrophages. Finally, the combination of an MMP9 inhibitor with TCR-T cells targeting EBV-positive tumors significantly inhibited the growth of xenografts in mice. CONCLUSIONS: MMP9 inhibitors improve TCR-T cell function suppressed by EBV-induced M2 macrophages. TCR-T-cell therapy combined with MMP9 inhibitors was an effective therapeutic strategy for EBV-positive solid tumors.


Assuntos
Antígenos CD , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Macrófagos , Metaloproteinase 9 da Matriz , Receptores de Superfície Celular , Animais , Camundongos , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Receptores de Superfície Celular/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Microambiente Tumoral , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Feminino , Linfócitos T/imunologia , Linfócitos T/metabolismo , Imunoterapia Adotiva/métodos
3.
Beilstein J Nanotechnol ; 15: 694-703, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919165

RESUMO

Multifrequency atomic force microscopy (AFM) utilizes the multimode operation of cantilevers to achieve rapid high-resolution imaging and extract multiple properties. However, the higher-order modal response of traditional rectangular cantilever is weaker in air, which affects the sensitivity of multifrequency AFM detection. To address this issue, we previously proposed a bridge/cantilever coupled system model to enhance the higher-order modal response of the cantilever. This model is simpler and less costly than other enhancement methods, making it easier to be widely used. However, previous studies were limited to theoretical analysis and preliminary simulations regarding ideal conditions. In this paper, we undertake a more comprehensive investigation of the coupled system, taking into account the influence of probe and excitation surface sizes on the modal response. To facilitate the exploration of the effectiveness and optimal conditions for the coupled system in practical applications, a macroscale experimental platform is established. By conducting finite element analysis and experiments, we compare the performance of the coupled system with that of traditional cantilevers and quantify the enhancement in higher-order modal response. Also, the optimal conditions for the enhancement of macroscale cantilever modal response are explored. Additionally, we also supplement the characteristics of this model, including increasing the modal frequency of the original cantilever and generating additional resonance peaks, demonstrating the significant potential of the coupled system in various fields of AFM.

4.
Plast Reconstr Surg Glob Open ; 12(5): e5845, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38798928

RESUMO

Background: Botulinum toxin type A (BTA) is becoming more and more prevalent as an injection agent in cosmetic surgery. However, there is an increasing amount of cases reporting unexpected adverse reactions related to BTA injection. BTA can invoke many kinds of hypersensitive reactions, some of which can be delayed-type or even fatal; hence, it is of crucial importance to pay close attention to atypical and early symptoms that may indicate the presence of BTA allergy in patients. Methods: In this study, we reported three cases of mild and unexpected BTA-related hypersensitive reaction with a symptom of nonpruritic erythema on the chest that happened after BTA treatment of upper facial wrinkles and proposed several suggestions based on our practical experience and literature review. Results: Two patients' symptoms were alleviated spontaneously, and one patient's were alleviated after taking oral corticosteroid. According to our literature review, we believe that these incidences indicate a kind of unreported allergic reaction relevant to botulinum toxin. Conclusions: We suggest clinicians consider warily patients' subsequent BTA injection schedule if any suspicious reaction occurs after treatment. We suggest that patients who experience nonpruritic erythema after botulinum toxin injection should suspend subsequent injection plans for at least 3 months to prevent more severe consequences.

5.
BMC Neurol ; 24(1): 164, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773425

RESUMO

BACKGROUND AND PURPOSE: The relationship between heart rate and the prognosis of patients with large vessel occlusion strokes treated with mechanical thrombectomy (MT) is not well established. This study aimed to evaluate the association of mean heart rate and heart rate variability (HRV) with the clinical outcomes after MT therapy. METHODS: Acute ischemic stroke patients undergoing MT therapy were prospectively recruited from March 2020 to November 2022. Their heart rate was collected every hour for the initial 72 h after MT procedure, and the variability of heart rate was measured by standard deviation (SD) and coefficient of variation (CV). All-cause mortality and worsening of functional outcome (change in modified Rankin Scale (mRS) score) at 3-month were captured. Binary logistic regression was used to evaluate the association between heart rate indicators and all-cause mortality. Ordinal logistic regression was used to evaluate the association between heart rate indicators and worsening of functional outcome. RESULTS: Among 191 MT-treated patients, 51(26.7%) patients died at 3-month after stroke. Increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were all associated with the increased risk of mortality (adjusted hazard ratio [aHR] with 95% CI: 1.29 [1.09-1.51], 1.19 [1.07-1.32], 1.14 [1.03-1.27]; respectively). Patients in the highest tertile of heart rate SD had an increased risk of mortality (4.62, 1.70-12.52). After using mRS as a continuous variable, we found increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were associated with the worsening of functional outcome (adjusted odds ratio [aOR] with 95% CI: 1.35 [1.11-1.64], 1.27 [1.05-1.53], 1.19 [1.02-1.40]; respectively). A linear relationship was observed between mean heart rate or heart rate SD and mortality; while all of the heart rate measures in this study showed a linear relationship with the worsening of functional outcome. CONCLUSIONS: Higher mean heart rate and HRV were associated with the increased risk of 3-month all-cause mortality and worse functional outcome after MT therapy for AIS patients.


Assuntos
Frequência Cardíaca , AVC Isquêmico , Trombectomia , Humanos , Masculino , Feminino , Idoso , Frequência Cardíaca/fisiologia , Pessoa de Meia-Idade , Trombectomia/métodos , Trombectomia/estatística & dados numéricos , AVC Isquêmico/mortalidade , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , AVC Isquêmico/fisiopatologia , Resultado do Tratamento , Idoso de 80 Anos ou mais , Estudos Prospectivos , Prognóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/fisiopatologia
6.
Front Nutr ; 11: 1361567, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650637

RESUMO

Background: Nonalcoholic fatty liver disease (NAFLD) stands a prevalent chronic liver condition significantly influenced by oxidative stress. We investigated the unclear relationship between antioxidant-rich diet and lifestyle and cardiovascular disease (CVD) prevalence rate and mortality in adult patients with NAFLD. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHAENS) spanning from 1999 to 2018 to investigate the association between adherence to an antioxidant-rich diet and lifestyle and the cardiovascular disease (CVD) prevalence rate and mortality in adult patients with NAFLD. The study employed the Oxidative Balance Score (OBS) to define antioxidant diet and lifestyle. Results: Including 8,670 adult patients with NAFLD, the study revealed an inverse association between OBS and the prevalence of most CVD conditions. Fully adjusted models demonstrated that each unit increase in diet OBS, lifestyle OBS, and overall OBS corresponded to a 2, 7, and 2% reduction in all-cause mortality, respectively. In models 2, findings revealed that lifestyle Q2 and Q3 were linked to reduced cancer mortality, whereas diet and overall OBS did not exhibit an association. Additionally, Stratified analysis revealed that age (<45 years) and education level (> high school) significantly influenced the association between the OBS and the prevalence of CVD. Conclusion: These results underscore the protective link between adherence to an antioxidant diet and lifestyle and a diminished prevalence of CVD and mortality in adults with NAFLD, particularly among younger and higher-educated populations.

7.
Ultramicroscopy ; 261: 113964, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38579523

RESUMO

Compressive sensing (CS) can reconstruct the rest information almost without distortion by advanced computational algorithm, which significantly simplifies the process of atomic force microscope (AFM) scanning with high imaging quality. In common CS-AFM, the partial measurements randomly come from the whole region to be measured, which easily leads to detail loss and poor image quality in regions of interest (ROIs). Consequently, important microscopic phenomena are missed probably. In this paper, we developed an adaptive under-sampling strategy for CS-AFM to optimize the process of sampling. Under a certain under-sampling ratio, the weight coefficient of ROIs and regions of base (ROBs) were set to control the distribution of under-sampling points and corresponding measurement matrix. A series of simulations were completed to demonstrate the relationship between the weight coefficient of ROIs and image quality. After that, we verified the effectiveness of the method on our homemade AFM. Through a lot of simulations and experiments, we demonstrated how the proposed method optimized the sampling process of CS-AFM, which speeded up the process of AFM imaging with high quality.

8.
Biomolecules ; 14(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38672450

RESUMO

Motilin is a gastrointestinal hormone that is mainly produced in the duodenum of mammals, and it is responsible for regulating appetite. However, the role and expression of motilin are poorly understood during starvation and the weaning stage, which is of great importance in the seeding cultivation of fish. In this study, the sequences of Yangtze sturgeon (Acipenser dabryanus Motilin (AdMotilin)) motilin receptor (AdMotilinR) were cloned and characterized. The results of tissue expression showed that by contrast with mammals, AdMotilin mRNA was richly expressed in the brain, whereas AdMotilinR was highly expressed in the stomach, duodenum, and brain. Weaning from a natural diet of T. Limnodrilus to commercial feed significantly promoted the expression of AdMotilin in the brain during the period from day 1 to day 10, and after re-feeding with T. Limnodrilus the change in expression of AdMotilin was partially reversed. Similarly, it was revealed that fasting increased the expression of AdMotilin in the brain (3 h, 6 h) and duodenum (3 h), and the expression of AdMotilinR in the brain (1 h) in a time-dependent manner. Furthermore, it was observed that peripheral injection of motilin-NH2 increased food intake and the filling index of the digestive tract in the Yangtze sturgeon, which was accompanied by the changes of AdMotilinR and appetite factors expression in the brain (POMC, CART, AGRP, NPY and CCK) and stomach (CCK). These results indicate that motilin acts as an indicator of nutritional status, and also serves as a novel orexigenic factor that stimulates food intake in Acipenser dabryanus. This study lays a strong foundation for the application of motilin as a biomarker in the estimation of hunger in juvenile Acipenser dabryanu during the weaning phase, and enhances the understanding of the role of motilin as a novel regulator of feeding in fish.


Assuntos
Comportamento Alimentar , Peixes , Motilina , Animais , Encéfalo/metabolismo , Proteínas de Peixes/metabolismo , Peixes/metabolismo , Peixes/genética , Peixes/fisiologia , Motilina/genética , Motilina/metabolismo , Motilina/farmacologia , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores dos Hormônios Gastrointestinais/genética , Receptores de Neuropeptídeos/metabolismo , Receptores de Neuropeptídeos/genética
9.
Food Chem Toxicol ; 188: 114686, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38663762

RESUMO

Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), two common types of phthalates, are known to cause reproductive and developmental toxicity in animals and humans. The reference doses (RfD) of DBP and DEHP should be determined by sensitive endpoints. We here aimed to identify sensitive endpoints for DBP- and DEHP-induced such toxicity using published literatures. By examining the impacts of maternal exposure to DBP or DEHP on anogenital distance (AGD) and semen quality of offspring, we discovered that DBP or DEHP caused AGD decline in boys but increase in girls with DBP being more potent and the first 14weeks of pregnancy being more susceptible, suggesting a chemical- and time-dependent phenomenon. We also identified AGD shortening and total sperm count reduction as two sensitive endpoints for DBP- or DEHP-induced reproductive and developmental toxicity, respectively. Based upon these two endpoints and the employment of the Bayesian benchmark dose approach with an uncertainty factor of 3,000, we estimated the RfD values of DBP and DEHP were 15 µg/kg/day and 36 µg/kg/day, respectively. Thus, we uncover previously unrecognized phenomena of DBP- or DEHP-induced reproductive and developmental toxicity and establish new and comparable or more conservative RfDs for the risk assessment of phthalates exposure in humans.


Assuntos
Dibutilftalato , Reprodução , Masculino , Humanos , Reprodução/efeitos dos fármacos , Feminino , Animais , Dibutilftalato/toxicidade , Gravidez , Dietilexilftalato/toxicidade , Ácidos Ftálicos/toxicidade , Exposição Materna/efeitos adversos
10.
Aesthetic Plast Surg ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429530

RESUMO

A rare case of trigeminal neuralgia following injections of Hyaluronic Acid and Botox was documented. In addressing the severe pain and swelling caused by the injection, a novel combination therapy was employed, notably including 5-fluorouracil. The significant improvement observed in this case not only provided clinical insights but also spurred further investigation into the underlying mechanisms linking trigeminal nerve damage to local dermal filler injections. The aim was to glean new medical perspectives and develop practical preventive strategies to mitigate such complications in future cases. This approach highlights the importance of understanding and addressing the potential neurological impacts of cosmetic procedures. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

11.
Food Chem Toxicol ; 186: 114576, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458533

RESUMO

Cinnabar is the naturally occurring mercuric sulfide (HgS) and concerns about its safety have been grown. However, the molecular mechanism of HgS-related neurotoxicity remains unclear. S-phase kinase-associated protein 1 (Skp1), identified as the target protein of HgS, plays a crucial role in the development of neurological diseases. This study aims to investigate the neurotoxic effects and molecular mechanism of HgS based on Skp1 using the Caenorhabditis elegans (C. elegans) model. We prepared the HgS nanoparticles and conducted a comparative analysis of neurobehavioral differences in both wild-type C. elegans (N2) and a transgenic strain of C. elegans (VC1241) with a knockout of the SKP1 homologous gene after exposure to HgS nanoparticles. Our results showed that HgS nanoparticles could suppress locomotion, defecation, egg-laying, and associative learning behaviors in N2 C. elegans, while no significant alterations were observed in the VC1241 C. elegans. Furthermore, we conducted a 4D label-free proteomics analysis and screened 504 key proteins significantly affected by HgS nanoparticles through Skp1. These proteins play pivotal roles in various pathways, including SNARE interactions in vesicular transport, TGF-beta signaling pathway, calcium signaling pathway, FoxO signaling pathway, etc. In summary, HgS nanoparticles at high doses suppress the neurobehavioral functions of C. elegans through a Skp1-dependent mechanism.


Assuntos
Proteínas de Caenorhabditis elegans , Compostos de Mercúrio , Nanopartículas , Animais , Caenorhabditis elegans/metabolismo , Proteínas Quinases Associadas a Fase S/genética , Compostos de Mercúrio/toxicidade , Nanopartículas/toxicidade , Proteínas de Caenorhabditis elegans/metabolismo
12.
Fish Physiol Biochem ; 50(3): 941-954, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38381278

RESUMO

Gastrin is an important intragastrointestinal hormone, but reports on its regulation of feeding behavior in fish are still scarce. This study aimed to determine the feeding regulatory function of gastrin in sturgeon. In this study, a gastrin/cholecystokinin-like peptide was identified in the genomes of sturgeon and proved to be gastrin by evolutionary tree analysis. Tissue distribution of gastrin and its receptor, cholecystokinin receptor B (CCKRB), showed that both had high mRNA abundance in the hypothalamus and gastrointestinal tract. In the duodenum, gastrin and CCKRB mRNAs were reduced at 1 h of fasting, and both were also observed in the stomach and hypothalamus in response to changes in feeding status. Sulfated gastrin 17 is the major form of gastrin in vivo. Therefore, we investigated the effect of sulfated gastrin 17 on feeding by intraperitoneal injection into Siberian sturgeon using sulfated gastrin 17. The results showed that gastrin 17 significantly reduced the cumulative feeding of Siberian sturgeon in the short term (1, 3 and 6 h) and long term (1, 2, 3, 4, 5 and 7 days). Finally, we explored the potential mechanism of feeding inhibition after intraperitoneal injection of gastrin 17 for 7 consecutive days. The results showed that gastrin 17 treatment significantly increased the mRNA levels of anorexigenic peptides (cart, cck and pyy), while it had no significant effect on the mRNA abundance of orexigenic peptides (npy and agrp). In addition, gastrin 17 treatment significantly affected the expression of appetite signaling pathways in the hypothalamus, such that the mRNA expression of ampkα1 was significantly reduced, whereas the mRNA abundance of stat3, mtor and s6k was significantly increased. In conclusion, the present study confirmed the anorectic effect of gastrin on Siberian sturgeon.


Assuntos
Peixes , Gastrinas , Receptor de Colecistocinina B , Animais , Gastrinas/metabolismo , Peixes/fisiologia , Peixes/metabolismo , Receptor de Colecistocinina B/metabolismo , Receptor de Colecistocinina B/genética , Comportamento Alimentar/efeitos dos fármacos , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Hipotálamo/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-38191049

RESUMO

Emerging findings point to a role for C1q/TNF-related protein 4 (CTRP4) in feeding in mammals. However, it remains unknown whether CTRP4 regulates feeding in fish. This study aimed to determine the feeding regulation function of CTRP4 in Siberian sturgeon (Acipenser baerii). In this study, the Siberian sturgeon ctrp4 (Abctrp4) gene was cloned, and Abctrp4 mRNA was shown to be highly expressed in the hypothalamus. In the hypothalamus, Abctrp4 mRNA decreased during fasting and reversed after refeeding. Subsequently, we obtained the AbCTRP4 recombinant protein by prokaryotic expression and optimized the expression and purification conditions. Siberian sturgeon (81.28 ± 14.75 g) were injected intraperitoneally using 30, 100, and 300 ng/g Body weight (BW) AbCTRP4 to investigate its effect on feeding. The results showed that 30, 100, and 300 ng/g BW of the AbCTRP4 significantly reduced the cumulative food intake of Siberian sturgeon at 1, 3, and 6 h. Finally, to investigate the potential mechanism of CTRP4 feeding inhibition, 300 ng/g BW AbCTRP4 was injected intraperitoneally. The findings demonstrated that AbCTRP4 treatment for 1 h significantly promoted the mRNA levels of anorexigenic peptides (pomc, cart, and leptin) while suppressing the mRNA abundances of orexigenic peptides (npy and agrp).In addition, the jak2/stat3 pathway in the hypothalamus was significantly activated after 1 h of AbCTRP4 treatment. In conclusion., this study confirms the anorexigenic effect of CTRP4 in Siberian sturgeon.


Assuntos
Apetite , Complemento C1q , Animais , Apetite/genética , Complemento C1q/metabolismo , Complemento C1q/farmacologia , Ingestão de Alimentos/fisiologia , Peixes/fisiologia , Peptídeos/genética , Peptídeos/farmacologia , Peptídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mamíferos/metabolismo
14.
Mol Biol Rep ; 51(1): 152, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236332

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor that originates in the nasopharyngeal mucosa and is common in China and Southeast Asian countries. Cancer cells reprogram glycolytic metabolism to promote their growth, survival and metastasis. Glycolysis plays an important role in NPC development, but the underlying mechanisms remain incompletely elucidated. Lactate dehydrogenase A (LDHA) is a crucial glycolytic enzyme, catalyzing the last step of glycolysis. This study aims to investigate the exact role of LDHA, which catalyzes the conversion of pyruvate into lactate, in NPC development. METHODS AND RESULTS: The western blot and immunohistochemical (IHC) results indicated that LDHA was significantly upregulated in NPC cells and clinical samples. LDHA knockdown by shRNA significantly inhibited NPC cell proliferation and invasion. Further knockdown of LDHA dramatically weakened the tumorigenicity of NPC cells in vivo. Mechanistic studies showed that LDHA activated TGF-ß-activated kinase 1 (TAK1) and subsequent nuclear factor κB (NF-κB) signaling to promote NPC cell proliferation and invasion. Exogenous lactate supplementation restored NPC cell proliferation and invasion inhibited by LDHA knockdown, and this restorative effect was reversed by NF-κB inhibitor (BAY 11-7082) or TAK1 inhibitor (5Z-7-oxozeaenol) treatment. Moreover, clinical sample analyses showed that LDHA expression was positively correlated with TAK1 Thr187 phosphorylation and poor prognosis. CONCLUSIONS: Our results suggest that LDHA and its major metabolite lactate drive NPC progression by regulating TAK1 and its downstream NF-κB signaling, which could become a therapeutic target in NPC.


Assuntos
Lactato Desidrogenase 5 , MAP Quinase Quinase Quinases , NF-kappa B , Neoplasias Nasofaríngeas , Humanos , Lactato Desidrogenase 5/genética , Ácido Láctico , MAP Quinase Quinase Quinases/metabolismo , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , NF-kappa B/metabolismo
15.
Int J Ophthalmol ; 16(12): 2041-2048, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38111952

RESUMO

AIM: To evaluate the efficacy of retinal laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) for hemorrhagic retinal arterial macroaneurysm (RAM). METHODS: This was a retrospective clinical study. Patients with hemorrhagic RAM were divided into 4 groups defined by different treatments: a retinal laser photocoagulation therapy monotherapy group, an anti-VEGF intravitreal injection monotherapy group, a laser and anti-VEGF combination therapy group, and an observation group. Visual acuity (VA), central macular thickness (CMT), and retinal hemorrhage area (RHA) were collected. RESULTS: Forty-seven eyes of 47 patients were enrolled. VA improved and had a significant difference between baseline and final in each treatment group (logMAR; laser group: 1.90±0.53 vs 1.05±0.63, P<0.001; anti-VEGF group: 1.75±0.63 vs 1.12±0.54, P=0.009; combination group: 1.76±0.38 vs 1.01±0.52, P<0.001); however, VA decreased and had no significant difference in observation group (1.63±0.51 vs 1.76±0.61, P=0.660). CMT decreased and had a significant difference between baseline and final in each group (laser group: 815.16±310.83 vs 252.05±83.90 µm, P<0.001; anti-VEGF group: 725.00±290.79 vs 203.56±69.89 µm, P=0.001; combination group: 595.50±186.51 vs 253.13±55.06 µm, P=0.001; observation group: 758.88±195.65 vs 267.00±120.90 µm, P=0.001). RHA were 28.99±28.15, 25.94±11.58, 19.64±8.97, and 27.45±13.76 mm2 in laser group, anti-VEGF group, combination group and observation group, respectively. RHA was statistically correlated with final VA (P=0.032) in the observation group. CONCLUSION: Both laser and anti-VEGF treatments are effective for hemorrhagic RAM. Combination therapy reduces the number of injections of anti-VEGF. RHA is a visual prognosis predictor in the natural history of hemorrhagic RAM.

16.
Plast Reconstr Surg Glob Open ; 11(10): e5356, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37908327

RESUMO

Hemihypertrophy is a rare congenital disorder that causes unequal growth of the extremities, trunk, face, or half of the body. We report a case of a 32-year-old woman with hemihypertrophy-related gastrocnemius hypertrophy treated with botulinum toxin A injection. The patient has received two botulinum toxin A injections, and we measured the thickness of the gastrocnemius muscle using ultrasound and measured the maximum circumference around the calf with the patient in the prone position. The patient's maximum calf circumference was reduced by 1 cm. The thickness of the medial head of the gastrocnemius was reduced by 0.3 cm, and the thickness of the lateral head of the gastrocnemius was reduced by 0.6 cm. Botulinum toxin A injection therapy was effective in treating hemihypertrophy-related gastrocnemius hypertrophy.

17.
BMC Ophthalmol ; 23(1): 473, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990182

RESUMO

OBJECTIVES: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED). METHODS: Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022. RESULTS: One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0 mg group was better than IVR 0.5 mg (average difference 0.07) and IVR 2.0 mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58. CONCLUSIONS: IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.


Assuntos
Degeneração Macular , Descolamento Retiniano , Humanos , Ranibizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Descolamento Retiniano/tratamento farmacológico , Metanálise em Rede , Fator A de Crescimento do Endotélio Vascular , Epitélio Pigmentado da Retina , Estudos Retrospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico
18.
Opt Express ; 31(21): 34648-34666, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37859216

RESUMO

The space-based gravitational wave detection mission, TianQin, requires high-level synchronization between independent clocks of all spacecrafts to extract the gravitational wave signals. It is necessary to measure the inter-spacecraft relative clock jitter based on laser phase-sideband clock transfer. The main challenge is the tracking and locking of clock sideband beatnote signals with low signal-to-noise ratio and frequency variation. In this paper, a systematic scheme of inter-spacecraft clock jitter readout is reported. The requirement of the clock transfer link for TianQin based on the time-delay interferometry algorithm is derived. A bi-directional laser interferometer system with a transmission optical power below 1 nW and a time delay of ∼50 µs is built up to demonstrate the weak-light clock transfer. In this scheme, frequency modulation is performed on the laser to simulate the inter-spacecraft Doppler frequency shift and its variation. Based on electrical and optical clock transfer comparison experiments, it is demonstrated that the GHz frequency synthesizer is the main noise source below the 50 mHz frequency range. The residual clock jitter noise introduced by the optical transfer link is below 40 fs/Hz1/2 above the 6 mHz frequency range, and the fractional frequency instability is less than 6.7 × 10-17 at 1000 s, which meets the requirement of the TianQin mission. Ultimately, The carrier phase measurement accuracy reaches 1 × 10-4 cycles/Hz1/2 above 6 mHz after differential clock noise correction using measured clock jitter.

19.
Math Biosci Eng ; 20(7): 12731-12749, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37501464

RESUMO

In the era of digital economy, enterprise research and development (R&D) tends to be open-source. Due to their limited resources, small and medium-sized enterprises (SMEs) can join open-source platforms to get additional creative resources and technical support. In this context, from the perspective of complex networks, the influence diffusion of SMEs after embedding open-source innovation networks is studied in this paper. First, an integrated simulation model including a network model, agent model and innovative diffusion model is constructed. Second, the influence diffusion strategy is proposed considering initial impact, embedding timing and connection mode (same-match and heterogeneous) of the enterprise. Third, the dynamic simulation of the influence diffusion process of SMEs demonstrates that embedding timing has a significant impact. There is no significant difference in the influence diffusion at the early and mature stages in the evolution process of open-source innovation networks. The initial impact of enterprises has a significant influence on the diffusion during the developing period, but the effect on its influence diffusion at the initial and mature stages is not obvious. Finally, in light of experiment results, it is clear that the open-source platform plays an important role on the growth of SMEs as evidenced by the close correlation between the spread of SMEs' influence within the open-source innovation network and the community's stage of development.

20.
Clin Cosmet Investig Dermatol ; 16: 1089-1094, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37123621

RESUMO

Introduction: SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare disease clinically characterized by a wide range of cutaneous and osteoarticular manifestations, involving multiple system impairments. Vasculitis is a rare comorbidity of SAPHO. Henoch-Schönlein purpura (HSP) is a vasculitis involving the capillaries and arterioles mediated by IgA immune complex. No case report of SAPHO syndrome with HSP was ever found. Case: Here we reported a case of SAPHO syndrome complicated with HSP and was successfully treated by methylprednisolone and tofacitinib. Discussion: Although the treat-to-target management of HSP and the first-line clinical medication have given some advices on the treatment. A precise treatment was still needed based on the pathogenesis of the comorbidity. The mechanism of the co-occurrence includes innate immunity and adapted immunity. Considering the active inflammatory reaction and the rapid disease progression, methylprednisolone and tofacitinib were prescribed. Conclusion: HSP is a new comorbidity of SAPHO. The spectrum of cutaneous small-vessel vasculitis in SAPHO syndrome was enriched. A new treatment approach for SAPHO with HSP was provided.

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