RESUMO
Xanthogranulomatous cholecystitis (XGC) is a rare type of cholecystitis that, despite being benign poses diagnostic challenges due to its low prevalence and need for consensus on diagnostic criteria. Consequently, distinguishing XGC from gallbladder cancer (GBC) is challenging, leading to clinical misdiagnoses. This article presents a case where a patient initially diagnosed with GBC was later found to have XGC.
RESUMO
Inflammatory retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) are prominent causes of blindness in industrialized countries. The complexity of these diseases, involving diverse cell types and pathways that give rise to a multifactorial pathogenesis, complicates drug discovery. As such, therapies exhibiting polypharmacology are expected to improve outcomes through broader disease stage coverage and beneficial spatiotemporal effects. We report herein the first dual modulator of PPARα and STING, two targets tied to disparate pathologies in retinal diseases. Recognizing structural similarities between a reported STING inhibitor SN-013 and our previously described PPARα agonist A229, we designed BH400, which agonizes PPARα (EC50 = 1.2 µM) and inhibits STING (IC50 = 8.1 µM). BH400 demonstrates superior protection over single-target PPARα or STING modulation in microglial and photoreceptor cells. These findings provide compelling evidence for the potential benefit of polypharmacology in common retinal diseases through dual PPARα/STING modulation, motivating further studies.
RESUMO
A novel Fe-MoOx nanozyme, engineered with enhanced peroxidase (POD)-like activity through strategic doping and the creation of oxygen vacancies, is introduced to catalyze the oxidation of TMB with high efficiency. Furthermore, Fe-MoOx is responsive to single electron transfer (SET) and hydrogen atom transfer (HAT) mechanisms related to antioxidants and can serve as a desirable nanozyme for total antioxidant capacity (TAC) determination. The TAC colorimetric platform can reach a low LOD of 0.512 µM in solution and 24.316 µM in the smartphone-mediated RGB hydrogel (AA as the standard). As proof of concept, the practical application in real samples was explored. The work paves a promising avenue to design diverse nanozymes for visual on-site inspection of food quality.
Assuntos
Antioxidantes , Colorimetria , Oxirredução , Antioxidantes/química , Antioxidantes/análise , Antioxidantes/metabolismo , Colorimetria/métodos , Catálise , Molibdênio/química , Limite de Detecção , Ferro/química , Benzidinas/química , Smartphone , Hidrogéis/química , Transporte de Elétrons , Técnicas Biossensoriais/métodos , Óxidos/químicaRESUMO
Obstructive sleep apnea (OSA) can lead to intestinal injury, endotoxemia, and disturbance of intestinal flora. Additionally, as a crucial component of the endocannabinoid system, some studies have demonstrated that cannabinoid 1 (CB1) receptors are closely linked to the multiple organ dysfunction triggered by OSA. However, the role of the CB1 receptor in alleviating OSA-induced colon injury remains unclear. Here, through the construction of the OSA classic model, we found that the colon tissue of chronic intermittent hypoxia (CIH)-induced mice exhibited an overexpression of the CB1 receptor. The results of hematoxylin-eosin staining and transmission electron microscopy revealed that inhibition of the CB1 receptor could decrease the gap between the mucosa and muscularis mucosae, alleviate mitochondrial swelling, reduce microvilli shedding, and promote the recovery of tight junctions of CIH-induced mice. Furthermore, CB1 receptor inhibition reduced the levels of metabolic endotoxemia and inflammatory responses, exhibiting significant protective effects on the colon injury caused by CIH. At the molecular level, through western blotting and real-time polymerase chain reaction techniques, we found that inhibiting the CB1 receptor can significantly increase the expression of ZO-1 and Occludin proteins, which are closely related to the maintenance of intestinal mucosal barrier function. Through 16S rRNA high-throughput sequencing and short-chain fatty acid (SCFA) determination, we found that inhibition of the CB1 receptor increased the diversity of the microbial flora and controlled the makeup of intestinal flora. Moreover, butyric acid concentration and the amount of SCFA-producing bacteria, such as Ruminococcaceae and Lachnospiraceae, were both markedly elevated by CB1 receptor inhibition. The results of the spearman correlation study indicated that Lachnospiraceae showed a positive association with both ZO-1 and Occludin but was negatively correlated with the colon CB1 receptor, IL-1ß, and TNF-α. According to this study, we found that inhibiting CB1 receptor can improve CIH-induced colon injury by regulating gut microbiota, reducing mucosal damage and promoting tight junction recovery. KEY POINTS: â¢CIH leads to overexpression of CB1 receptor in colon tissue. â¢CIH causes intestinal flora disorder, intestinal mucosal damage, and disruption of tight junctions. â¢Inhibition of CB1 receptor can alleviate the colon injury caused by CIH through regulating the gut microbiota, reducing mucosal injury, and promoting tight junction recovery.
Assuntos
Colo , Modelos Animais de Doenças , Mucosa Intestinal , Receptor CB1 de Canabinoide , Animais , Receptor CB1 de Canabinoide/metabolismo , Receptor CB1 de Canabinoide/genética , Camundongos , Colo/patologia , Colo/microbiologia , Colo/metabolismo , Masculino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Hipóxia/metabolismo , Camundongos Endogâmicos C57BL , Proteína da Zônula de Oclusão-1/metabolismo , Ocludina/metabolismo , Ocludina/genética , Microbioma Gastrointestinal , Junções Íntimas/metabolismoRESUMO
OBJECTIVES: To observe the effect of acupuncture and moxibustion on arterial elasticity in patients with early carotid atherosclerosis. METHODS: A total of 62 patients with early carotid atherosclerosis were randomly divided into a blank group (12 cases, 1 cases dropped-off), a sham-acupuncture group (25 cases, 5 cases dropped-off) and an acupuncture group (25 cases, 3 cases dropped-off). Patients in the acupuncture group received acupuncture treatment, including â acupunctureï¼Baihui (GV20), Yintang (GV24+), Renying (ST9), Neiguan (PC6), Yanglingquan (GB34)ï¼â¡moxibustionï¼Yinqiguiyuan (Zhongwan ï¼»CV12ï¼½, Xiawan ï¼»CV10ï¼½, Qihai ï¼»CV6ï¼½, Guanyuan ï¼»CV4ï¼½), Sihua (Geshu ï¼»BL17ï¼½, Danshu ï¼»BL19ï¼½)ï¼â¢Intradermal needleï¼Xinshu (BL15), Danshu (BL19). Patients in the sham acupuncture group received placebo acupuncture, moxibustion, an intradermal needle, and the acupoints were the same as the acupuncture group. The above treatments were performed twice a week for 12 weeks. No intervention was given to the patients in the blank group. Diet and lifestyle education was given to the three groups. The ultrafast pulse wave velocity, including beginning-systolic pulse wave velocity (BS) and end-systolic pulse wave velocity (ES), was observed before treatment and 1, 2, 3 months after treatment in the three groups. The blood lipid level and platelet count (PLT) at each time point were observed. The safety of the treatments was also evaluated. RESULTS: Compared with those before treatment, the BS and ES values of both sides in the acupuncture group decreased at 2 and 3 months after treatment (P<0.05). Compared with the blank group, the bilateral ES of the acupuncture group were decreased at 2 months after treatment (P<0.05), and the bilateral BS and ES were decreased at 3 months (P<0.05). Compared with the sham-acupuncture group, the acupuncture group showed a decrease in left BS and left ES after 3 months of treatment (P<0.05), and the overall decrease on the left side of the acupuncture group was better than that on the right side. There were no significant differences between three groups in the levels of blood lipid and PLT at each time point. No serious adverse safety events occurred in the three groups during the treatment. CONCLUSIONS: Acupuncture and moxibustion therapy can improve arterial elasticity in patients with early carotid atherosclerosis, and it is safe and effective.
Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Doenças das Artérias Carótidas , Moxibustão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doenças das Artérias Carótidas/terapia , Doenças das Artérias Carótidas/fisiopatologia , Elasticidade , Adulto , Artérias Carótidas/fisiopatologiaRESUMO
This study selected 15 key predictors of the maximum of 8-hour averaged ozone (O3) concentration (O3-8h), using the O3 concentration of Haikou and ERA5 reanalysis data from 2015 to 2020, and constructed a multiple linear regression (MLR) model, support vector machine (SVM) model, and BP neural network (BPNN) model, to predict and test the O3-8h concentration of Haikou in 2021. The results showed that the absolute value of correlation coefficients between the O3-8h and related key prediction factors was mainly among 0.2 and 0.507. The 1 000 hPa relative humidity (RH1000), wind direction (WD1000), and 875 hPa meridional wind (v875) showed a good indicative effect on the O3-8h, with the absolute correlation value exceeding 0.4. The three prediction models could predict the seasonal variation in the O3-8h in Haikou, which was larger in the winter half year and smaller in the summer half year. The root mean square error(RMSE) was the smallest (22.29 µg·m-3) in the BPNN model. The correlation coefficients between the predicted values of three statistical models and observations were ranked as 0.733 (BPNN) > 0.724 (SVM) > 0.591 (MLR), all passing the 99.9% significance test. For the prediction of the O3-8h level, we found that TS scores of these three prediction models decreased with the increase in O3-8h concentration level. Relatively, the point over rate and not hit rate increased with the rise in O3-8h concentration level. TS scores of the SVM and BPNN model were relatively larger than those of MLR, especially in the light pollution level with TS scores remaining above 70%, indicating a better prediction capability.
RESUMO
RATIONALE: Negative pressure pulmonary edema (NPPE) is an acute onset of non-cardiogenic interstitial pulmonary edema, commonly seen among surgical patients after extubation from general aneasthesia. It is mainly caused by rapid inspiration with acute upper airway obstruction resulting in significant negative thoracic pressure. PATIENT CONCERNS: A 24-year-old female patient who underwent laparoscopic cholecystectomy under general anesthesia and developed NPPE postoperatively. DIAGNOSES: Her main clinical manifestation was coughing up pink foamy sputum; postoperative CT showed increased texture in both lungs and bilateral ground glass opacities. INTERVENTIONS: Diuretics and steroids were used, and symptomatic supportive treatments such as oxygen were given. OUTCOMES: After treatment, on the fourth post-operative day, her symptoms were relieved and her vital signs were stable enough for her to be discharged. LESSONS: Although this is a rare and severe complication, the prognosis of NPPE is good when it is managed with proper diagnosis and treatment.
Assuntos
Obstrução das Vias Respiratórias , Colecistectomia Laparoscópica , Edema Pulmonar , Humanos , Feminino , Adulto Jovem , Adulto , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/etiologia , Colecistectomia Laparoscópica/efeitos adversos , Diuréticos/uso terapêutico , Oxigênio , Anestesia Geral/efeitos adversos , Obstrução das Vias Respiratórias/complicaçõesRESUMO
OBJECTIVE: Kallistatin (KST), also known as SERPIN A4, is a circulating, broadly acting human plasma protein with pleiotropic properties. Clinical studies in humans revealed reduced KST levels in obesity. The exact role of KST in glucose and energy homeostasis in the setting of insulin resistance and type 2 diabetes is currently unknown. METHODS: Kallistatin mRNA expression in human subcutaneous white adipose tissue (sWAT) of 47 people with overweight to obesity of the clinical trial "Comparison of Low Fat and Low Carbohydrate Diets With Respect to Weight Loss and Metabolic Effects (B-SMART)" was measured. Moreover, we studied transgenic mice systemically overexpressing human KST (hKST-TG) and wild type littermate control mice (WT) under normal chow (NCD) and high-fat diet (HFD) conditions. RESULTS: In sWAT of people with overweight to obesity, KST mRNA increased after diet-induced weight loss. On NCD, we did not observe differences between hKST-TG and WT mice. Under HFD conditions, body weight, body fat and liver fat content did not differ between genotypes. Yet, during intraperitoneal glucose tolerance tests (ipGTT) insulin excursions and HOMA-IR were lower in hKST-TG (4.42 ± 0.87 AU, WT vs. 2.20 ± 0.27 AU, hKST-TG, p < 0.05). Hyperinsulinemic euglycemic clamp studies with tracer-labeled glucose infusion confirmed improved insulin sensitivity by higher glucose infusion rates in hKST-TG mice (31.5 ± 1.78 mg/kg/min, hKST-TG vs. 18.1 ± 1.67 mg/kg/min, WT, p < 0.05). Improved insulin sensitivity was driven by reduced hepatic insulin resistance (clamp hepatic glucose output: 7.7 ± 1.9 mg/kg/min, hKST-TG vs 12.2 ± 0.8 mg/kg/min, WT, p < 0.05), providing evidence for direct insulin sensitizing effects of KST for the first time. Insulin sensitivity was differentially affected in skeletal muscle and adipose tissue. Mechanistically, we observed reduced Wnt signaling in the liver but not in skeletal muscle, which may explain the effect. CONCLUSIONS: KST expression increases after weight loss in sWAT from people with obesity. Furthermore, human KST ameliorates diet-induced hepatic insulin resistance in mice, while differentially affecting skeletal muscle and adipose tissue insulin sensitivity. Thus, KST may be an interesting, yet challenging, therapeutic target for patients with obesity and insulin resistance.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Doenças não Transmissíveis , Serpinas , Humanos , Camundongos , Animais , Glucose/metabolismo , Resistência à Insulina/fisiologia , Serpinas/genética , Sobrepeso , Insulina/metabolismo , Obesidade/metabolismo , Camundongos Transgênicos , Dieta Hiperlipídica/efeitos adversos , Homeostase , Redução de Peso , RNA Mensageiro/metabolismoRESUMO
Laser wakefield acceleration is paving the way for the next generation of electron accelerators, for their own sake and as radiation sources. A controllable dual-wake injection scheme is put forward here to generate an ultrashort triplet electron bunch with high brightness and high polarization, employing a radially polarized laser as a driver. We find that the dual wakes can be driven by both transverse and longitudinal components of the laser field in the quasiblowout regime, sustaining the laser-modulated wakefield which facilitates the subcycle and transversely split injection of the triplet bunch. Polarization of the triplet bunch can be highly preserved due to the laser-assisted collective spin precession and the noncanceled transverse spins. In our three-dimensional particle-in-cell simulations, the triplet electron bunch, with duration about 500 as, six-dimensional brightness exceeding 10^{14} A/m^{2}/0.1% and polarization over 80%, can be generated using a few-terawatt laser. Such an electron bunch could play an essential role in many applications, such as ultrafast imaging, nuclear structure and high-energy physics studies, and the operation of coherent radiation sources.
RESUMO
BACKGROUND AND AIM: A novel study found interferon enhanced antitumor activity of anti-PD-1-based immunotherapy and played a crucial role in improving efficacy on HCC, but the opposite results about the efficacy of interferon on HBV-related HCC were obtained from previous clinical studies and meta-analyses. Thus, this meta-analysis aimed to re-evaluate whether interferon could improve survival and reduce recurrence of patients with HBV-related HCC after curative surgery. METHODS: MEDLINE/PubMed, Cochrane Library, EMBASE, Web of Science and CNKI were searched for eligible studies from inception to November 2022 and a meta-analysis was done. RESULTS: 10 trials with a total of 2062 subjects were screened. Interferon significantly improved 1-, 2-, 3- and 5-year OS and 1-, 2- and 3-year DFS, and reduced 2-, 3- and 5-year recurrence rates of patients with HBV-related HCC after curative surgery. However, interferon did not improve 8-year OS and 5-year DFS, did not reduce 1-year recurrence rate. CONCLUSIONS: Interferon may significantly reduce recurrence and improve DFS of patients with HBV-related HCC after curative surgery, and finally improve the OS. However, the efficacy advantage may gradually weaken as time goes on. The clinical application of interferon combined with NAs recommended in this meta-analysis is needed to be further studied.
Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Vírus da Hepatite B , Neoplasias Hepáticas/patologia , Interferons/uso terapêutico , Imunoterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do Tratamento , Hepatectomia , Hepatite B/complicações , Hepatite B/tratamento farmacológicoRESUMO
Corneal dysfunctions associated with Diabetes Mellitus (DM), termed diabetic keratopathy (DK), can cause impaired vision and/or blindness. Hypoxia affects both Type 1 (T1DM) and Type 2 (T2DM) surprisingly, the role of hypoxia in DK is unexplored. The aim of this study was to examine the impact of hypoxia in vitro on primary human corneal stromal cells derived from Healthy (HCFs), and diabetic (T1DMs and T2DMs) subjects, by exposing them to normoxic (21% O2) or hypoxic (2% O2) conditions through 2D and 3D in vitro models. Our data revealed that hypoxia affected T2DMs by slowing their wound healing capacity, leading to significant alterations in oxidative stress-related markers, mitochondrial health, cellular homeostasis, and endoplasmic reticulum health (ER) along with fibrotic development. In T1DMs, hypoxia significantly modulated markers related to membrane permeabilization, oxidative stress via apoptotic marker (BAX), and protein degradation. Hypoxic environment induced oxidative stress (NOQ1 mediated reduction of superoxide in T1DMs and Nrf2 mediated oxidative stress in T2DMs), modulation in mitochondrial health (Heat shock protein 27 (HSP27), and dysregulation of cellular homeostasis (HSP90) in both T1DMs and T2DMs. This data underscores the significant impact of hypoxia on the diabetic cornea. Further studies are warranted to delineate the complex interactions.
Assuntos
Doenças da Córnea , Diabetes Mellitus , Humanos , Substância Própria/metabolismo , Córnea/metabolismo , Doenças da Córnea/etiologia , Doenças da Córnea/metabolismo , Hipóxia/metabolismoRESUMO
BACKGROUND AND PURPOSE: Whether symptomatic unruptured intracranial aneurysms (UIAs) lead to change in circulating inflammation remains unclear. This study aims to evaluate the role of hematological inflammatory indicators in predicting symptomatic UIA. METHODS: Adult patients diagnosed with saccular intracranial aneurysm from March 2019 to September 2023 were recruited retrospectively. Clinical and laboratory data, including the white blood cells (WBC), neutral counts (NEUT), lymphocyte counts (LYM), and monocyte counts (MONO) of each patient, were collected. The neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were calculated as NLR = NEUT/LYM, LMR = LYM/MONO, SII = PLT*NEUT/LYM. The hematological inflammatory indicators were compared in symptomatic saccular and asymptomatic UIA patients. Multivariable logistic regression analyses were performed to explore the factors predicting symptomatic UIA. RESULTS: One hundred and fifty UIA patients with a mean age of 58.5 ± 12.4 were included, of which 68% were females. The NLR and LMR were significantly associated with symptomatic UIA, and the association remained in small UIAs (< 7 mm). The multiple logistic regression analysis showed that NLR was independently associated with symptomatic UIA. On ROC curve analysis, the optimal cutoff value of NLR to differentiate symptomatic from asymptomatic was 2.38. In addition, LMR was significantly associated with symptomatic UIA smaller than 7 mm. CONCLUSION: There was a significant correlation between NLR and symptomatic UIA. The NLR was independently associated with symptomatic UIA.
Assuntos
Aneurisma Intracraniano , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico , Neutrófilos , Estudos Retrospectivos , Linfócitos , Contagem de LinfócitosRESUMO
BACKGROUND: Infertility is a prevalent global condition, and emerging reproductive technologies may enhance its evaluation and treatment. Understanding the current features of randomized clinical trials in infertility is crucial for improving study design and ensuring the translation of results for patient benefits. OBJECTIVES: To investigate the primary characteristics of randomized clinical trials related to infertility and areas where require improvement. MATERIALS AND METHODS: We conducted a search on the International Clinical Trials Registry platform for eligible infertility trials between 2003 and 2022. The distribution ratio of various characteristics uploaded by infertility-related studies on the platform was analyzed and compared according to sex and registration year. RESULTS: Out of the total trials, 85.3% (1,906) included only women, 8.6% (192) included only men, and 6.1% (136) included couples. The majority of retrieved trials followed a parallel arm design (91.0%) and were non-industry-funded (92.2%), with a median planned sample size of 131 patients (interquartile range 75-270). Among these trials, 54.5% (1,217) were conducted in Asia. The most common primary purpose of infertility-related trials was treatment (88.8%), with over half of the investigated interventions focusing on medication (57.9%). DISCUSSION: Asia is the leading region for research, and the drug therapy is still widely used and updated. However, support care for infertile couples has also received some preference. Areas that require improvement and promotion include addressing male infertility and focusing on underserved regions like Africa. The results also highlight deficiencies in trial registration and masking methods, emphasizing the need for better regulation and facilitation of infertility trials in the post-COVID-19 era. CONCLUSION: Based on the current status of infertility RCT studies, greater attention should be paid to infertile men and populations in underdeveloped regions like Africa in future studies, together with a standardized registration and implementation procedures.
Assuntos
Infertilidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Masculino , Infertilidade/terapia , Feminino , Técnicas de Reprodução AssistidaRESUMO
Fenofibrate has shown therapeutic effects on diabetic retinopathy. However, fenofibrate can be rapidly cleared from the eye after a single intravitreal injection. Here, we aim to develop fenofibrate loaded PLGA microparticles (Feno-MP) with high drug loading and sustained in vitro release up to 6 months suitable for intravitreal injection. First, orthogonal array experimental design was applied for formulation optimization. The selected formulation parameters were used to formulate Feno-MP using homogenization method and direct membrane emulsification method. Both methods generated Feno-MP with high drug loading and sustained in vitro drug release more than 140 days. Unlike the polydisperse Feno-MP prepared using homogenization method, membrane emulsification method generated Feno-MP with uniform size distribution. By controlling the membrane pore size, 1.5 µm, 8 µm and 16 µm Feno-MP were formulated and we found that larger Feno-MP demonstrated higher drug loading, more sustained drug release in vitro with less burst drug release than the smaller Feno-MP. In conclusion, we developed Feno-MP with high drug loading and sustained release profile, and elucidated that changing the particle size could have notable impacts on drug loading and release kinetics. Formulating Feno-MP with uniform size distribution by membrane emulsification method would benefit the batch-to-batch repeatability.
Assuntos
Fenofibrato , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Liberação Controlada de Fármacos , Tamanho da Partícula , Microesferas , Preparações de Ação RetardadaRESUMO
INTRODUCTION/BACKGROUND: Positive surgical margins (PSMs) after radical prostatectomy (RP) can increase the risk of biochemical recurrence in prostate cancer (PCa) patients. However, the prediction of the likelihood of PSMs in patients undergoing similar surgical procedures remains a challenge. We aim to develop a predictive model for PSMs in patients undergoing non-nerve-sparing RP. PATIENTS AND METHODS: In this retrospective study, we analyzed data from PCa patients who underwent minimally invasive non-nerve-sparing RP at our hospital between June 2017 and June 2021. We identified independent risk factors associated with PSMs using clinical and MRI-based parameters in univariate and multivariate logistic regression analyzes. These factors were then used to develop a nomogram for predicting the probability of PSMs. The predictive performance was validated using calibration and receiver operating characteristic curve, area under the curve ,and decision curve analysis. RESULTS: Multivariate analyzes revealed prostate-specific antigen density, tumor size, tumor location at the apex, tumor contact length, extracapsular extension (ECE) level, and apparent diffusion coefficient value as independent risk factors. A nomogram was developed and validated with high accuracy (C-index = 0.78). Furthermore, we found that 44.2% of patients diagnosed with organ-confined disease had ECE after surgery, and 29.1% of patients with Gleason scores ≤7 had higher pathological scores. Interestingly, the tumor burden calculated from PCa biopsy cores was overestimated when compared to postoperative PCa specimens. CONCLUSION: We developed a reliable nomogram for predicting the risk of PSMs in PCa patients undergoing non-nerve-sparing RP. The study highlights the importance of incorporating these parameters in personalized surgical management.
Assuntos
Margens de Excisão , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/etiologia , Fatores de Risco , Antígeno Prostático Específico , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND:Myocardial patches are used as an effective way to repair damaged myocardium,and there is controversy over which cells to use to make myocardial patches and how to maximize the therapeutic effect of myocardial patches in vivo. OBJECTIVE:To find out the best way to make myocardial patches by overviewing the cellular sources of myocardial patches and strategies for perfecting them. METHODS:The first author searched PubMed and Web of Science databases by using"cell sheet,cell patch,cardiomyocytes,cardiac progenitor cells,fibroblasts,embryonic stem cell,mesenchymal stem cells"as English search terms,and searched CNKI and Wanfang databases by using"myocardial patch,biological 3D printing,myocardial"as Chinese search terms.After enrollment screening,94 articles were ultimately included in the result analysis. RESULTS AND CONCLUSION:(1)The cellular sources of myocardial patches are mainly divided into three categories:somatic cells,monoenergetic stem cells,and pluripotent stem cells,respectively.There are rich sources of cells for myocardial patches,but not all of them are suitable for making myocardial patches,e.g.,myocardial patches made from fibroblasts and skeletal myoblasts carry a risk of arrhythmogenicity,and mesenchymal stem cells have a short in vivo duration of action and ethical concerns.With the discovery of induced multifunctional stem cells,a reliable source of cells for making myocardial patches is available.(2)There are two methods of making myocardial patches.One is using cell sheet technology.The other is using biological 3D printing technology.Cell sheet technology can preserve the extracellular matrix components intact and can maximally mimic the cell growth ring in vivo.However,it is still difficult to obtain myocardial patches with three-dimensional structure by cell sheet technology.Biologicasl 3D printing technology,however,can be used to obtain myocardial patches with three-dimensional structures through computerized personalized design.(3)The strategies for perfecting myocardial patches mainly include:making myocardial patches after co-cultivation of multiple cells,improving the ink formulation and scaffold composition in biological 3D printing technology,improving the therapeutic effect of myocardial patches,suppressing immune rejection after transplantation,and perfecting the differentiation and cultivation protocols of stem cells.(4)There is no optimal cell source or method for making myocardial patches,and myocardial patches obtained from a particular cell or technique alone often do not achieve the desired therapeutic effect.Therefore,researchers need to choose the appropriate strategy for making myocardial patches based on the desired therapeutic effect before making them.
RESUMO
Traditional photonuclear reactions primarily excite giant dipole resonances, making the measurement of isovector giant resonances with higher multipolarities a great challenge. In this Letter, the manipulation of collective excitations of different multipole transitions in even-even nuclei via vortex γ photons is investigated. We develop the calculation method for photonuclear cross sections induced by the vortex γ photon beam using the fully self-consistent random-phase approximation plus particle-vibration coupling (RPA+PVC) model based on Skyrme density functional. We find that the electromagnetic transitions with multipolarity J<|m_{γ}| are forbidden for vortex γ photons due to the angular momentum conservation, with m_{γ} being the projection of total angular momentum of γ photon on its propagation direction. For instance, this allows for probing the isovector giant quadrupole resonance without interference from dipole transitions using vortex γ photons with m_{γ}=2. Furthermore, the electromagnetic transition with J=|m_{γ}|+1 vanishes at a specific polar angle. Therefore, the giant resonances with specific multipolarity can be extracted via vortex γ photons. Moreover, the vortex properties of γ photons can be meticulously diagnosed by measuring the nuclear photon-absorption cross section. Our method opens new avenues for photonuclear excitations, generation of coherent γ photon laser and precise detection of vortex particles, and consequently, has significant impact on nuclear physics, nuclear astrophysics and strong laser physics.
RESUMO
Injuries to the retinal pigment epithelium (RPE) and outer retina often result in the accumulation of retinal microglia within the subretinal space. These subretinal microglia play crucial roles in inflammation and resolution, but the mechanisms governing their functions are still largely unknown. Our previous research highlighted the protective functions of choroidal γδ T cells in response to RPE injury. In the current study, we employed single-cell RNA sequencing approach to characterize the profiles of immune cells in mouse choroid. We found that γδ T cells were the primary producer of interleukin-17 (IL-17) in the choroid. IL-17 signaled through its receptor on the RPE, subsequently triggering the production of interleukin-6. This cascade of cytokines initiated a metabolic reprogramming of subretinal microglia, enhancing their capacity for lipid metabolism. RPE-specific knockout of IL-17 receptor A led to the dysfunction of subretinal microglia and RPE pathology. Collectively, our findings suggest that responding to RPE injury, the choroidal γδ T cells can initiate a protective signaling cascade that ensures the proper functioning of subretinal microglia.
Assuntos
Degeneração Macular , Degeneração Retiniana , Animais , Camundongos , Citocinas/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Degeneração Macular/patologia , Retina/metabolismo , Degeneração Retiniana/metabolismo , Epitélio Pigmentado da Retina/metabolismoRESUMO
BACKGROUND: COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009). METHODS: In the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18-59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 µg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009. RESULTS: All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination. CONCLUSION: LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Método Duplo-Cego , População do Leste Asiático , Imunogenicidade da Vacina , SARS-CoV-2 , Vacinas de mRNARESUMO
We put forward a novel method for producing ultrarelativistic high-density high-polarization positrons through a single-shot interaction of a strong laser with a tilted solid foil. In our method, the driving laser ionizes the target, and the emitted electrons are accelerated and subsequently generate abundant γ photons via the nonlinear Compton scattering, dominated by the laser. These γ photons then generate polarized positrons via the nonlinear Breit-Wheeler process, dominated by a strong self-generated quasistatic magnetic field B^{S}. We find that placing the foil at an appropriate angle can result in a directional orientation of B^{S}, thereby polarizing positrons. Manipulating the laser polarization direction can control the angle between the γ photon polarization and B^{S}, significantly enhancing the positron polarization degree. Our spin-resolved quantum electrodynamics particle-in-cell simulations demonstrate that employing a laser with a peak intensity of about 10^{23} W/cm^{2} can obtain dense (â³10^{18} cm^{-3}) polarized positrons with an average polarization degree of about 70% and a yield of above 0.1 nC per shot. Moreover, our method is feasible using currently available or upcoming laser facilities and robust with respect to the laser and target parameters. Such high-density high-polarization positrons hold great significance in laboratory astrophysics, high-energy physics, and new physics beyond the standard model.