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Tissue-specific gene knockout by CRISPR/Cas9 is a powerful approach for characterizing gene functions during development. However, this approach has not been successfully applied to most Drosophila tissues, including the Drosophila neuromuscular junction (NMJ). To expand tissue-specific CRISPR to this powerful model system, here we present a CRISPR-mediated tissue-restricted mutagenesis (CRISPR-TRiM) toolkit for knocking out genes in motoneurons, muscles, and glial cells. We validated the efficacy of CRISPR-TRiM by knocking out multiple genes in each tissue, demonstrated its orthogonal use with the Gal4/UAS binary expression system, and showed simultaneous knockout of multiple redundant genes. We used CRISPR-TRiM to discover an essential role for SNARE components in NMJ maintenance. Furthermore, we demonstrate that the canonical ESCRT pathway suppresses NMJ bouton growth by downregulating retrograde Gbb signaling. Lastly, we found that axon termini of motoneurons rely on ESCRT-mediated intra-axonal membrane trafficking to release extracellular vesicles at the NMJ. Thus, we have successfully developed an NMJ CRISPR mutagenesis approach which we used to reveal genes important for NMJ structural plasticity.
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The development of electrochemical energy storage devices has a decisive impact on clean renewable energy. Herein, novel ultrafast rechargeable hybrid sodium dual-ion capacitors (HSDICs) were designed by using ultrathin carbon film (UCF) as the cathode material. The UCF is synthesized by a simple low temperature catalytic route followed by an acid leaching process. UCF owns a large adsorption interface and number of additional active sites, which is due to the nitrogen doping. In addition, there exists several short-range order carbons on the surface of UCF, which are beneficial for anionic storage. An ultrafast rechargeable remarkable performance, remarkable anion hybrid storage capability and outstanding structure stability is fully tapped employing UCF as cathode for HSDICs. The electrochemical performance of UCF in a half-cell system at the operating voltage between 1.0 and 4.8 V, achieving an admirable specific discharge capacity of 358.52 mAh·g-1at 500 mA·g-1, and a high capacity retention ratio of 98.42% after cycling 2500 times at 1000 mA·g-1, respectively. Besides, with the support ofex-situTEM and EDS mapping, the structural stability principle and anionic hybrid storage mechanism of UCF electrode are investigated in depth. In the full-cell system, HSDICs with the UCF as cathode and hard carbon as anode also presents a super-long cycle stability (80.62% capacity retention ratio after cycling 1300 times at 1000 mA·g-1).
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BACKGROUND: The risk factors for hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT) are unclear. Therefore, we conducted this systematic review and meta-analysis to investigate the risk factors for HC in children undergoing HSCT. METHODS: We performed this meta-analysis by retrieving studies from PubMed, EMBASE, and the Cochrane Library up to October 10, 2023, and analyzing those that met the inclusion criteria. I2 statistics were used to evaluate heterogeneity. RESULTS: Twelve studies, including 2,764 patients, were analyzed. Male sex (odds ratio [OR] = 1.52; 95% confidence interval [CI], 1.16-2.00; p = 0.003, I2 = 0%), allogeneic donor (OR = 5.28; 95% CI, 2.60-10.74; p < 0.00001, I2 = 0%), human leukocyte antigen (HLA) mismatched donor (OR = 1.86; 95% CI, 1.00-3.44; p = 0.05, I2 = 31%), unrelated donor (OR = 1.58; 95% CI, 1.10-2.28; p = 0.01, I2 = 1%), myeloablative conditioning (MAC) (OR = 3.17; 95% CI, 1.26-7.97; p = 0.01, I2 = 0%), busulfan (OR = 2.18; 95% CI, 1.33-3.58; p = 0.002, I2 = 0%) or anti-thymoglobulin (OR = 1.65; 95% CI, 1.07-2.54; p = 0.02, I2 = 16%) use, and cytomegalovirus (CMV) reactivation (OR = 2.64; 95% CI, 1.44-4.82; p = 0.002, I2 = 0%) were risk factors for HC in children undergoing HSCT. CONCLUSIONS: Male sex, allogeneic donor, HLA-mismatched, unrelated donor, MAC, use of busulfan or anti-thymoglobulin, and CMV reactivation are risk factors for HC in children undergoing HSCT.
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Cistitis Hemorrágica , Trasplante de Células Madre Hematopoyéticas , Hemorragia , Niño , Femenino , Humanos , Masculino , Cistitis Hemorrágica/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemorragia/etiología , Factores de Riesgo , Factores Sexuales , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
PURPOSE: This study aimed to evaluate the impact of the pressure gradient on papilledema after stenting in patients with idiopathic intracranial hypertension (IIH) patients and venous sinus stenosis (VSS). MATERIALS AND METHODS: In this prospective cohort study, we examined 121 patients with IIH and VSS who underwent stenting. The papilledema Frisen grade at the 1-month follow-up was used as a grouping factor (favorable outcome: 0-1; unfavorable outcome: 2-5). We used multivariable logistic regression modeling to determine independent predictors of favorable outcome. The performance of the prediction model was evaluated using a receiver operating characteristic (ROC) analysis. RESULTS: A total of 96 patients had papilledema grades 0 to 1, and 25 patients had papilledema grades 2 to 5. Patients with the first group had significantly lower gradient pressures preoperatively (15.2 mmHg vs. 21.4 mmHg, p=0.001) and postoperatively (2 mmHg vs. 3.3 mmHg, p=0.002) relative to those in the second group. Multivariate analysis indicated that preoperative pressure gradient (odds ratio [OR] = 1.119; 95% confidence interval [CI] = 1.034-1.211]) and postoperative pressure gradient (OR = 1.498; 95% CI = 1.147-1.957) were independent predictors of favorable outcome. In the ROC analysis, the cut-off pressure gradient for the highest sensitivity (0.44) and specificity (0.874) was 22.75 mmHg, with a Youden's index of 0.314. Survival analysis demonstrated that patients with a preoperative pressure gradient <22.75 mmHg had more rapid improvement of papilledema than did those with a pressure gradient >22.75 mmHg (mean+SD: 2.639+0.382 [95% CI: 1.890-3.388] versus mean+SD: 3.882+0.884 [95% CI: 2.149-5.616]; p=0.004). CONCLUSION: A significant reduction in the pressure gradient appears to be strongly correlated with the success of VSS in patients with IIH. A higher preoperative pressure gradient may reduce stenting efficacy in patients with IIH. CLINICAL IMPACT: Venous sinus stenting has the potential to yield substantial clinical advantages in individuals diagnosed with idiopathic intracranial hypertension with venous sinus stenosis. Nevertheless, a heightened preoperative pressure gradient could lead to less favorable results. Thus, the early adoption of venous sinus stenting is advised to avert additional irreversible clinical deterioration among idiopathic intracranial hypertension patients with venous sinus stenosis.
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PURPOSE: Mitochondrial dysfunction plays an important role in the development of obesity and obesity-associated metabolic diseases. METHODS: In this study, we dynamically observed the characteristics of mitochondrial damage in a rat model of diet-induced obesity (DIO). From the 2nd to the 10th week, animals were killed every 2 weeks and the heart, liver, kidney, and testicular tissues were harvested. Mitochondria were isolated and the activities of respiratory chain complexes I, II, III, and IV as well as the 8-Hydroxy-2-deoxy Guanosine content were determined. Reactive oxygen species and malondialdehyde were measured. RESULTS: Mitochondrial damages were observed in the heart and liver of DIO and DR rats, and the damages occurred later in DR group than that in DIO group. The mitochondrial membrane potential of heart and liver decreased in DIO and DR groups. The activity of the heart mitochondria complexes I, III, and IV (composing NADH oxidative respiratory) was higher in the early stage of DIO and lower in the end of week 10. The higher activity of the liver complexes I, III, and IV was found until the end of week 10 in DIO and DR groups, accompanied with enhanced oxidative stress. Besides, mitochondrial DNA damages were observed in all tissues. CONCLUSION: In DIO rats, the heart mitochondrial dysfunction occurred first and the liver presented the strongest compensatory ability against oxidative stress.
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Dieta Alta en Grasa/efectos adversos , Transporte de Electrón/fisiología , Obesidad/complicaciones , Estrés Oxidativo/fisiología , Animales , Masculino , Malondialdehído/metabolismo , Mitocondrias/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de OxígenoRESUMEN
Habitat is of great importance in determining the trophic transfer of pollutants in freshwater ecosystems; however, the major factors influencing chemical trophodynamics in pelagic and benthic food webs remain unclear. This study investigated the levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), polycyclic aromatic hydrocarbons (PAHs), and substituted PAHs (s-PAHs) in 2 plankton species, 6 invertebrate species, and 10 fish species collected from Lake Dianchi in southern China. Relatively high concentrations of PAHs and s-PAHs were detected with total concentrations of 11.4-1400 ng/g wet weight (ww) and 5.3-115 ng/g ww, respectively. Stable isotope analysis and stomach content analysis were applied to quantitatively determine the trophic level of individual organisms and discriminate between pelagic and benthic pathways, and the trophodynamics of the detected compounds in the two food webs were assessed. P,p'-DDE was found to exhibit relatively higher trophic magnification rate in the pelagic food web than in the benthic food web. In contrast, PAHs and s-PAHs exhibited greater dilution rates along the trophic levels in the pelagic food web. The lower species differences of pollutants accumulated in benthic organisms compared to pelagic organisms is attributable to extra uptake via ingested sediment in benthos. The average uptake proportions of PAHs and s-PAHs via ingested sediment in benthic biotas were estimated to be 31-77%, and that of p,p'-DDE was 46%. The uptake routes are of importance for assessing the trophic magnification potentials of organic pollutants, especially in eutrophic freshwater ecosystems.
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Cadena Alimentaria , Contaminantes Químicos del Agua , Animales , China , Monitoreo del Ambiente , Peces , LagosRESUMEN
The purified total sterols and ß-sitosterol extracted from Sargassum horneri were evaluated for their antidepressant-like activity using the forced swim test (FST) and tail suspension test (TST) in mice. Total sterols and ß-sitosterol significantly reduced the immobility time in the FST and TST. Total sterols were administered orally for 7 days at doses of 50, 100, and 200 mg/kg, and ß-sitosterol was administered intraperitoneally at doses of 10, 20, and 30 mg/kg. ß-sitosterol had no effect on locomotor activity in the open field test. In addition, total sterols and ß-sitosterol significantly increased NE, 5-HT, and the metabolite 5-HIAA in the mouse brain, suggesting that the antidepressant-like activity may be mediated through these neurotransmitters.
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Antidepresivos/química , Antidepresivos/farmacología , Sargassum/química , Sitoesteroles/química , Sitoesteroles/farmacología , Esteroles/química , Esteroles/farmacología , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Suspensión Trasera/métodos , Ácido Hidroxiindolacético/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Actividad Motora/efectos de los fármacos , Neurotransmisores/metabolismo , Serotonina/metabolismo , Natación/fisiologíaRESUMEN
OBJECTIVE: To realize the oxidative damage of kidney mitochondrial complex in obese rats induced by high-fat diet and investigate the protective effects of sulforaphane against the damage. METHODS: Eighty-eight adult male SD rats were used, after 1 week adaptability feeding, 8 rats were selected as control group and given low-fat diet. The other 80 rats were given high-fat diet. After 2 weeks, the 32 diet-induced obesity models were choosen whose weight gain was higher than 40%. The 32 rats were randomly divided into 4 groups, i.e. high fat group, high fat+sulforaphane low dose group, high fat+sulforaphane middle dose group and high fat+sulforaphane high dose group. The rats in the sulforaphane low, middle and high dose groups were orally administered with sulforaphane 5, 10 and 20 mg/kg, all the 4 groups were kept feeding high-fat diet for 5 weeks. All rats were sacrificed and their kidneys were removed to assay the index of oxidative damages. RESULTS: The content of ROS (0.26 ± 0.04) and MDA((0.87 ± 0.05) U/mg) in the hight-fat group were significantly higher than those in the control group((0.20 ± 0.02),(0.57 ± 0.08) U/mg)(t values were -3.02 and -4.72, P < 0.05). The activity of T-AOC((0.43 ± 0.04) U/mg) and MMP (12.09 ± 1.56) were lower than the control group ((0.48 ± 0.04 U/mg, (16.08 ± 3.12) )(t values were 2.06 and 2.28, P < 0.05). Gavage intervention with sulforaphane, the MDA amount ((0.67 ± 0.05), (0.55 ± 0.05), (0.56 ± 0.07) U/mg) in the sulforaphane low, middle and high dose groups were lower than the hight-fat group ((0.87 ± 0.05) U/mg (t values were 3.65, 5.71 and 5.60. P < 0.05). The activity of T-AOC ((0.49 ± 0.05), (0.55 ± 0.05), (0.54 ± 0.04) U/mg), T-SOD ((61.07 ± 2.79), (55.95 ± 2.39), (60.26 ± 6.02) U/mg) and the level of MMP ((17.17 ± 2.52), (18.24 ± 2.54), (18.21 ± 3.65)) were higher than in the high-fat group ((0.43 ± 0.04) U/mg,(47.22 ± 2.43) U/mg,(12.09 ± 1.56)) (tT-AOC values were -2.36, -4.83 and -4.30; tT-SOD values were -6.37, -4.71 and -5.99; tMMP values were -2.90, -3.52 and -3.50, P < 0.05). The activity of GSH-Px in the sulforaphane low and middle dose groups ((69.12 ± 8.63), (64.43 ± 6.58) U/mg) were higher than those in the high-fat group((53.03 ± 5.70) U/mg)(t values were -3.82 and -2.71, P < 0.05). But there were no significant difference between the high dose group ((60.02 ± 7.05) U/mg) and the high-fat group (t = -1.66, P > 0.05). CONCLUSION: High-fat diet can induce the mitochondrial oxidative dysfunction in kidney, and sulforaphane shows protective effect on the kidney mitochondrial complex from oxidative damage in obese rats induced by high-fat diet.
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Dieta Alta en Grasa , Isotiocianatos , Riñón , Mitocondrias , Estrés Oxidativo , Animales , Dieta , Masculino , Obesidad , Ratas , Ratas Endogámicas , SulfóxidosRESUMEN
With the global aging population, addressing prevalent age-related conditions such as osteoporosis and sarcopenia is crucial. Traditional nutritional strategies focusing on single nutrients like calcium, vitamin D, or protein have limitations, prompting a nuanced exploration of the relationship between aging, nutrition, and musculoskeletal health. This cross-sectional study examines the complex interplay between dietary intake of macronutrients, common micronutrients, and water, as well as their association with musculoskeletal health in adults aged 50 to 80 years, using U.S. National Health and Nutrition Examination Survey data (NHANES). Employing multiple linear regression, restricted cubic splines, weighted quantile sum (WQS), and quantile-based g-computation (QGC) regression models, our initial analysis using the WQS model revealed that a one-quartile increase in mixed macronutrient intake was associated with a significant 0.009 unit increase in bone mineral density (BMD) and a 0.670 unit increase in grip strength, while a similar increase in mixed micronutrient intake showed a 0.007 unit increase in BMD and a 0.442 unit increase in grip strength. Our findings highlight the importance of a balanced dietary approach in promoting musculoskeletal health in the elderly, offering holistic strategies for overall well-being.
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Densidad Ósea , Micronutrientes , Nutrientes , Encuestas Nutricionales , Humanos , Anciano , Micronutrientes/administración & dosificación , Masculino , Femenino , Nutrientes/administración & dosificación , Persona de Mediana Edad , Estudios Transversales , Anciano de 80 o más Años , Densidad Ósea/efectos de los fármacos , Estado Nutricional , Envejecimiento/fisiología , Dieta/métodos , Fuerza de la Mano , Osteoporosis/prevención & controlRESUMEN
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) using umbilical cord blood is a valuable therapy option for patients with acute leukemia (AL). Acute graft-versus-host disease (aGVHD) remains the most frequently encountered complication. This study investigated risk factors for aGVHD and assessed whether post-transplant serum ferritin (SF) within 2 weeks is a potential biomarker for aGVHD in pediatric patients with AL undergoing umbilical cord blood transplantation (UCBT). MATERIAL AND METHODS We conducted a retrospective cohort study of 71 patients with AL who underwent UCBT at the Children's Hospital of Soochow University between 2017 and 2022. We evaluated several factors related to aGVHD. Univariate and multivariate analyses were performed using the proportional subdistribution hazard regression model of Fine and Gray. Analyses of overall survival (OS) were performed using the Kaplan-Meier method, and differences were compared using log-rank tests. RESULTS Of the 71 patients, 23 (32.4%) experienced grade II-IV aGVHD, of whom 18 (25.4%) developed grade III-IV aGVHD. Patients with grade II-IV and III-IV aGVHD had worse 5-year OS (69.4±10%, p=0.01; and 60.6±11.6, P=0.007, respectively). Conditioning intensity was a risk factor for grade III-IV aGVHD (HR: 0.34, 95% CI: 0.13-0.89, P=0.027). An SF level >1650 ng/mL within 2 weeks post-transplant was associated with an increased risk of severe aGVHD (HR: 3.61, 95% CI: 1.09-11.97, P=0.036). CONCLUSIONS Post-transplant SF within 2 weeks was a potential biomarker for developing severe aGVHD. Higher levels of post-transplant SF are associated with a higher incidence of grade II-IV aGVHD and grade III-IV aGVHD.
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Biomarcadores , Trasplante de Células Madre de Sangre del Cordón Umbilical , Ferritinas , Enfermedad Injerto contra Huésped , Humanos , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/diagnóstico , Masculino , Femenino , Ferritinas/sangre , Niño , Estudios Retrospectivos , Preescolar , Biomarcadores/sangre , Adolescente , Lactante , Enfermedad Aguda , Leucemia/sangre , Leucemia/terapia , Factores de Riesgo , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/terapiaRESUMEN
BACKGROUND: Traditional metrics such as body mass index (BMI) and waist circumference (WC) fail to accurately assess the health outcomes associated with abdominal adiposity, because they neglect the intricacies of adipose tissue distribution. Notably, the variability in body composition scaled to height remains underexplored in Chinese demographics. This study introduces height-normalised indices of abdominal adiposity using computed tomography (CT) scans and further assesses their associations with various health outcomes. METHODS: In a large, diverse Chinese population (n = 1054 healthy individuals; n = 1159 with dyslipidemia; n = 803 with diabetes; n = 1289 with cardio-cerebrovascular diseases; n = 1108 with cancers; and n = 509 with abnormal bone mas), abdominal CT scans were performed and allometric growth model analyses were used to derive height-normalised indices (body composition/heightß). Logistic regression models assessed the associations between these indices and health outcomes. RESULTS: Distinct scaling powers were observed for visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total abdominal adipose tissue (TAT), as well as for sagittal diameter (SAD), with marked sex differences. Powers for VAT were 1.786 ± 1.270 for males and 1.274 ± 0.692 for females. Powers for SAT were 2.266 ± 0.856 for males and 1.656 ± 0.497 for females. Powers for TAT were 2.141 ± 0.967 for males and 1.438 ± 0.489 for females. Powers for SAD were 0.646 ± 0.217 for males and 0.678 ± 0.141 for females. After controlling for age, BMI and WC, VAT/heightß, TAT/heightß and SAD/heightß retained their significantly positive associations with the odds of health outcomes, whereas SAT/heightß did not. CONCLUSIONS: Our findings endorse the clinical utility of height-normalised indices, particularly VAT/heightß, TAT/heightß and SAD/heightß, in health outcomes assessment. These indices, grounded in robust empirical data, underscore the necessity of a nuanced approach in obesity-related health evaluations, advocating for a departure from conventional methods like BMI.
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PURPOSE: To investigate the association between pathological myopia (PM) and immunological/inflammatory markers and to identify the possible risk factors for the formation of myopic choroidal neovascularization (mCNV). METHODS: One hundred fourteen unrelated subjects were recruited: 63 PM patients (PM group) with spherical equivalent of at least -8.00 diopters (range, -8.00 to -25.00) and axial length exceeding 26.5 mm, accompanied by characteristic pathologic changes, and 51 emmetropic age- and sex-matched individuals (control group) with spherical equivalent within ±1.0 diopter in both eyes. In the PM group, patients were assigned to two subgroups, mCNV group and no CNV group, according to the results of fluorescein angiography. Serum high-sensitivity C-reactive protein (hs-CRP) and complement profile (C3, C4, and CH50) were assayed. Statistical analysis was performed between the two groups. Binary logistic regression analysis was used to analyze the relative risk factors that were associated with the development of mCNV in the PM group patients. RESULTS: The range of axial length was 26.50 to 37.08 mm in the PM group and 22.32 to 24.56 mm in the control group. There were 24 patients in the mCNV group and 39 patients in the no CNV group. The PM group patients had significantly higher serum hs-CRP (p = 0.033), C3 (p = 0.004), and CH50 (p < 0.001) compared with the control group patients. There were no significant differences between the two groups for C4 level (p = 0.071). Binary logistic regression analysis, which included hs-CRP, C3, C4, CH50, age, and sex as covariates, showed that C3 (p = 0.03) and age (p = 0.01) were risk factors for mCNV, whereas serum hs-CRP, C4, CH50, and sex were not statistically significant predictors of mCNV in the PM group patients (p > 0.05). CONCLUSIONS: Our data support the hypothesis that immunological/inflammatory markers, namely hs-CRP, C3, and CH50 may play an important role in the development of PM, and that C3 level may be a predictive risk factor for mCNV formation.
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Proteína C-Reactiva/metabolismo , Proteínas del Sistema Complemento/metabolismo , Miopía Degenerativa/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Femenino , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Miopía Degenerativa/diagnóstico , Miopía Degenerativa/fisiopatología , Refracción Ocular , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
PDT-SPACE is an open-source software tool that automates interstitial photodynamic therapy treatment planning by providing patient-specific placement of light sources to destroy a tumor while minimizing healthy tissue damage. This work extends PDT-SPACE in two ways. The first enhancement allows specification of clinical access constraints on light source insertion to avoid penetrating critical structures and to minimize surgical complexity. Constraining fiber access to a single burr hole of adequate size increases healthy tissue damage by 10%. The second enhancement generates an initial placement of light sources as a starting point for refinement, rather than requiring entry of a starting solution by the clinician. This feature improves productivity and also leads to solutions with 4.5% less healthy tissue damage. The two features are used in concert to perform simulations of various surgery options of virtual glioblastoma multiforme brain tumors.
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INTRODUCTION: Anti-vascular endothelial growth factor (anti-VEGF) injection was widely used in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV); however, the systemic and local levels of vascular endothelial growth factor (VEGF)-B were seldom detected before. This study was conducted to detect and compare the aqueous humor and plasma VEGF-B levels in nAMD and PCV before and after anti-VEGF therapy. METHODS: Concentrations of VEGF-B in aqueous humor and plasma of individuals with nAMD (n = 10), PCV (n = 22), and age-related cataract controls (n = 12) were measured by enzyme-linked immunosorbent assay. Ranibizumab was injected intravitreally in patients monthly for three consecutive months. Before each injection in patients and at the baseline of controls, blood and aqueous humor samples were collected. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were collected before each injection in patient groups. The differences of BCVA, CRT, and VEGF-B levels in aqueous humor and plasma between groups before and after anti-VEGF therapy were compared. RESULTS: VEGF-B was overexpressed in aqueous humor and plasma of nAMD and PCV groups compared with control group (P < 0.05), but no statistically significant difference existed across nAMD and PCV groups (P > 0.05). Moreover, there were no obvious difference in levels of VEGF-B in aqueous humor and plasma within the treatment groups after anti-VEGF treatment (P > 0.05). The mean CRT in the nAMD group was thinner than that in the PCV group at baseline (P < 0.01). After injections, the CRT obviously declined in both groups (P < 0.05). There was no correlation between CRT reduction and high VEGF-B expression in aqueous humor and plasma of treatment groups. CONCLUSION: Overexpression of VEGF-B locally and systemically in patients with nAMD and PCV indicated that elevated VEGF-B concentrations were relevant to the disease processes. Ranibizumab did not influence the levels of VEGF-B in the real world. CRT might help to distinguish PCV from nAMD.
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Tissue-specific gene knockout by CRISPR/Cas9 is a powerful approach for characterizing gene functions in animal development. However, this approach has been successfully applied in only a small number of Drosophila tissues. The Drosophila motor nervous system is an excellent model system for studying the biology of neuromuscular junction (NMJ). To expand tissue-specific CRISPR to the Drosophila motor system, here we present a CRISPR-mediated tissue-restricted mutagenesis (CRISPR-TRiM) toolkit for knocking out genes in motoneurons, muscles, and glial cells. We validated the efficacy of this toolkit by knocking out known genes in each tissue, demonstrated its orthogonal use with the Gal4/UAS binary expression system, and showed simultaneous knockout of multiple redundant genes. Using these tools, we discovered an essential role for SNARE pathways in NMJ maintenance. Furthermore, we demonstrate that the canonical ESCRT pathway suppresses NMJ bouton growth by downregulating the retrograde Gbb signaling. Lastly, we found that axon termini of motoneurons rely on ESCRT-mediated intra-axonal membrane trafficking to lease extracellular vesicles at the NMJ.
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BACKGROUND: Osteoporosis and obesity are closely related, and the relationships between different types of obesity and osteoporosis are inconsistent. OBJECTIVE: Our objective was to summarize earlier data concerning the association between osteoporosis and obesity (general and central), and to compare the impacts of these two obesity indicators on osteoporosis. METHODS: From inception to May 2021, a comprehensive search in electronic bibliographic databases was conducted, and the search was updated in December 2021, July 2022 and June 2023. The data were independently extracted and evaluated by two investigators from epidemiological studies that reported the impact of obesity on the odds of incident osteoporosis. RESULTS: There were 24 studies included in the final analysis when it came to general obesity measured by body mass index (BMI). Individuals with overweight and obesity had decreased odds of osteoporosis (odds ratio (OR), 0.451, 95% confidence intervals (CIs): 0.366-0.557). Sensitivity analyses showed that both overweight and obesity were decreased odds of osteoporosis, with reductions of 48.6% and 70.1%, respectively (OR, 0.514, 95% CI: 0.407-0.649; OR, 0.299, 95% CI: 0.207-0.433). Conversely, individuals classified as underweight were found to have higher odds of osteoporosis (OR, 2.540, 95% CI: 1.483-4.350). In term of central obesity, the final analysis consisted of 7 studies. No significant association was observed between central obesity and osteoporosis (OR, 0.913, 95% CI: 0.761-1.096). CONCLUSIONS: General overweight and obesity were associated with lower odds of developing osteoporosis, whereas underweight was associated with higher odds. However, central obesity did not show a significant association with osteoporosis. These findings underscore the importance of considering the impact of obesity on osteoporosis. Further research is necessary to reinforce the evidence and validate our findings.
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Sobrepeso , Delgadez , Humanos , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Obesidad Abdominal , Obesidad/complicaciones , Obesidad/epidemiología , Índice de Masa CorporalRESUMEN
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity. OBJECTIVE: To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes. METHODS: This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models. RESULTS: Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m2, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects. CONCLUSIONS: The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.
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Receptor del Péptido 1 Similar al Glucagón , Sobrepeso , Humanos , Sobrepeso/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Obesidad/tratamiento farmacológico , Peso Corporal , Pérdida de PesoRESUMEN
BACKGROUND: This prospective cohort study compared the outcomes of stenting and medical treatment for patients with idiopathic intracranial hypertension (IIH) and venous sinus stenosis (VSS). METHODS: In this single-center cohort study, patients with IIH and VSS were evaluated between January 2014 and December 2019 with follow-up periods of 1, 3, and 6 months. The patients received either stenting or medical treatment. The two groups underwent 1:1 matching using propensity score analysis, and the clinical outcomes were compared. RESULTS: Following 1:1 matching, 36 patients who underwent stenting and 36 who underwent medical treatment were matched. The median improvements in the papilledema Frisén grade were greater in the stenting group at 1 month (-2 vs 0), 3 months (-3 vs -1), and 6 months (-3 vs -1) than in the medical treatment group. Patients who received stenting treatment had a significantly higher prevalence of complete resolution of their respective symptoms (headache, tinnitus, or visual disturbances) at 3 months (58.3% vs 13.9%, OR 8.68, 95% CI 2.74 to 27.52) and 6 months (80.6% vs 22.2%, OR 14.50, 95% CI 4.64 to 45.32) than those receiving medical treatment. CONCLUSIONS: This matched-control study shows that stenting has a greater efficacy rate and rapid resolution of papilledema and its respective symptoms compared with medical treatment.
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Hipertensión Intracraneal , Papiledema , Seudotumor Cerebral , Humanos , Seudotumor Cerebral/cirugía , Seudotumor Cerebral/etiología , Papiledema/terapia , Estudios de Cohortes , Estudios Prospectivos , Resultado del Tratamiento , Stents/efectos adversos , Constricción Patológica/etiología , Senos Craneales , Hipertensión Intracraneal/terapia , Estudios RetrospectivosRESUMEN
PURPOSE: This study aimed to identify predictors of rapid improvement of papilledema after stenting and develop a simple preintervention scale. METHODS: A prospective cohort of idiopathic intracranial hypertension (IIH) with venous sinus stenosis (VSS) treated with stenting in a tertiary hospital from January 2014 to December 2019 was reviewed. We categorized papilledema improvement into favorable (grades 0-1) and unfavorable (grades 2-5). We employed logistic regression analysis to find the predictive factors and develop the predictive scale. We then estimated the performance of the scale using the ROC curve and Hosmer-Lemeshow test. RESULTS: There were 110 patients who underwent venous sinus stenting, with a mean age of 37.1 years and a predominance of females (77.3%). A total of 85 patients had a favorable outcome following stenting, while 25 patients had an unfavorable outcome. The results of the multivariate analysis indicate that lower preoperative pressure gradients (odds ratio, OR: 4.01; 95% confidence interval, CI: 1.27-12.68), stenosis rates (OR: 4.16; 95% CI: 1.11-15.56), and preoperative papilledema grades (OR: 2.92; 95% CI: 1.44-5.91) were independently associated with rapid improvement of papilledema following stenting treatment. The 3item scale exhibited good discrimination with an area under the curve (AOC) of 0.81 (95% CI 0.72-0.89, pâ¯< 0.001), as well as acceptable calibration determined by the Hosmer-Lemeshow test (Pâ¯= 0.42). The optimal cut-off value of the scale (range 0-6 points) was ≥â¯4 points, with a sensitivity of 72%, specificity of 73%, and accuracy of 78%. CONCLUSION: The presence of lower preoperative pressure gradients, stenosis severity, and preoperative status of papilledema were identified as positive predictors of rapid improvement of the papilledema following stenting in IIH patients. The 3item scale provides a promising preintervention predictive model for predicting rapid response following stenting treatment in IIH patients with VSS.
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Papiledema , Seudotumor Cerebral , Femenino , Humanos , Adulto , Masculino , Seudotumor Cerebral/complicaciones , Seudotumor Cerebral/cirugía , Papiledema/terapia , Constricción Patológica , Estudios Prospectivos , Resultado del Tratamiento , Estudios Retrospectivos , Stents , Senos CranealesRESUMEN
Fungal endophthalmitis is a devastating infectious disease, with a poor visual prognosis and even possibility of eyeball enucleated. In recent years, the incidence of fungal endophthalmitis remarkably increased due to widely use of broad-spectrum antibiotics and corticosteroid hormone. This pose a challenge to ophthalmologists and their capacity of treating fungal endophthalmitis need to be improved. It is necessary to introduce the present status and progress in fungal endophthalmitis treatment focus on medications, surgery and its etiological examination, especially the use of newer antifungal agents, including voriconazole and liposomal amphotericin B.