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BACKGROUND: Infraorbital neuralgia is a refractory facial pain that may cause various psychological disorders. There is no optimal treatment for infraorbital neuralgia because few relevant studies have been conducted. Pulsed radiofrequency (PRF) is a minimally invasive procedure that has been proven effective in treating trigeminal neuralgia and other painful diseases. Our previous study demonstrated that high-voltage PRF was effective in patients with infraorbital neuralgia. However, there is little literature on the long-term follow-up of infraorbital neuralgia treated with high-voltage PRF with a large sample size. OBJECTIVES: To explore the long-term effectiveness and safety of high-voltage PRF guided by computed tomography for patients with infraorbital neuralgia who failed conservative treatment. STUDY DESIGN: Monocentric, retrospective, observational study. SETTING: This study enrolled patients with infraorbital neuralgia who failed conservative treatment for infraorbital neuralgia and who underwent a high-voltage PRF procedure at the Department of Pain Management in Beiging Tiantan Hospital. METHODS: From January 2013 through June 2022, a total of 223 patients were included in this study; 16 were excluded according to the exclusion criteria. Finally, the medical records of 207 patients were extracted and analyzed including demographic data, intraoperative records, pain-related baseline, data and side effects. Treatment efficacy was evaluated using the Barrow Neurological Institute scores for pain. The Barrow Neurological Institute pain intensity score, onset time, perioperative complications and the time of recurrence were routinely followed up at month one, month 3, month 6 and every year postoperatively. Recurrence-free survival curves were presented by a Kaplan-Meier plot. RESULTS: The initial pain relief rate after the high-voltage PRF treatment was 86.0%. The cumulative recurrence-free survival rates were 85.5% (at month one), 82.6% (at month 3), 77.8% (at month 6), 65.7%(at month 12), 61.7% (at month 24), 55.8% (at month 48), 47.6% (at month 96) and 45.2% (at month 120) postoperatively. The median follow-up time of the 207 patients was 67.0 months (interquartile range, 38.0-93.0 months; range from 12 months to 125 months), with a median recurrence-free time of 80 months according to the Kaplan-Meier estimator. LIMITATIONS: This was a retrospective observational study. Multicenter, prospective, randomized controlled studies should be conducted. In addition, the optimal parameters for PRF treatment of infraorbital neuralgia need to be further explored. CONCLUSION: Computed tomography-guided high-voltage PRF treatment provides a minimally invasive and effective treatment option for patients with infraorbital neuralgia who fail conservative treatment, which could be considered as a preferred treatment before more invasive treatments.
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Tratamento por Radiofrequência Pulsada , Humanos , Estudos Retrospectivos , Tratamento por Radiofrequência Pulsada/métodos , Seguimentos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Adulto , Neuralgia do Trigêmeo/terapia , Neuralgia do Trigêmeo/cirurgiaRESUMO
BACKGROUND: Gasserian ganglion-targeted conventional and pulsed radiofrequency treatments are percutaneous procedures performed for drug-refractory trigeminal neuralgia. However, ideal outcomes are not always achieved with these procedures; frequent postprocedural complications and therapeutic ineffectiveness are also of major concern. OBJECTIVES: This study was conducted to investigate a novel strategy for effective, uncomplicated pain relief in patients with drug-refractory trigeminal neuralgia. STUDY DESIGN: A multicenter, retrospective, observational study. SETTING: Participating centers were Beijing Tiantan Hospital and Sanbo Brain Hospital. METHODS: From January 2010 through December 2019, a total of 2,087 patients with drug-refractory trigeminal neuralgia were included in the current study. Of them, 143 underwent sequential conventional radiofrequency treatment and 1,944 underwent conventional radiofrequency treatment only. The primary outcome was being pain free at 24 months postprocedure; multiple secondary outcomes were compared between treatments before and after propensity score matching. RESULTS: At the 24-month follow-up, sequential radiofrequency treatment provided a higher pain-free outcome than conventional radiofrequency treatment (0.93 [95% CI, 0.92-0.94]) vs 0.89, (95% CI, 0.84-0.94; P = 0.04); hazard ratio, 1.703 (95% CI, 1.01-2.86). For the 124 propensity score-matched pairs, there was no significant difference between groups, although pain-free outcomes were numerically higher in the sequential radiofrequency treatment group (0.93 [95% CI, 0.89-0.98]) vs 0.90 (95% CI, 0.85-0.96; P = 0.3); hazard ratio, 0.653 (95% CI, 0.27-1.60). Notably, sequential radiofrequency treatment correlated with fewer overall postprocedural complications than conventional radiofrequency treatment, despite propensity score matching analysis (14/143 vs 723/1944, relative risk, 0.69 (95% CI, 0.65-0.74; P < 0.001); 11/124 vs 45/124, relative risk 0.69 (95% CI, 0.60-0.80; P < 0.001). LIMITATIONS: Procedural parameters and quality of life evaluation by treatment were not analyzed and cost data were not collected. CONCLUSION: Sequential radiofrequency treatment has the potential to provide effective, uncomplicated, pain-free outcomes.
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Pontuação de Propensão , Neuralgia do Trigêmeo , Humanos , Neuralgia do Trigêmeo/cirurgia , Neuralgia do Trigêmeo/terapia , Neuralgia do Trigêmeo/radioterapia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Tratamento por Radiofrequência Pulsada/métodos , Manejo da Dor/métodosRESUMO
The substantial promotion of hydrogen evolution reaction (HER) catalytic performance relies on the breakup of the Sabatier principle, which can be achieved by the alternation of the support and electronic metal support interaction (EMSI) is noticed. Due to the utilization of tungsten disulfides as support for platinum (Pt@WS2), surprisingly, Pt@WS2 demands only 31 mV overpotential to attain 10 mA cm-2 in acidic HER test, corresponding to a 2.5-fold higher mass activity than benchmarked Pt/C. The pH dependent electrochemical measurements associated with H2-TPD and in-situ Raman spectroscopy indicate a hydrogen spillover involved HER mechanism is confirmed. The WS2 support triggers a higher hydrogen binding strength for Pt leading to the increment in hydrogen concentration at Pt sites proved by upshifted d band center as well as lower Gibbs free energy of hydrogen, favourable for hydrogen spillover. Besides, the WS2 shows a comparably lower effect on Gibbs free energy for different Pt layers (-0.50 eV layer-1) than carbon black (-0.88 eV layer-1) contributing to a better Pt utilization. Also, the theoretical calculation suggests the hydrogen spillover occurs on the 3rd Pt layer in Pt@WS2; moreover, the energy barrier is lowered with increment in hydrogen coverage on Pt.
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Establishing an effective system to measure formaldehyde (HCHO) content in food is of great significance due to food safety concern. Inspired by the mechanism of HCHO-induced protein denaturation and its effect on ion/molecule transport in nanochannels, a bioinspired microchannel-based electrochemiluminescence (ECL) sensor was constructed for HCHO detection. Benefiting from the water solubility of HCHO, the molecules rapidly spread and enriched at the ethylenediamine (EDA) functionalized microchannel interface. The reaction between EDA and HCHO significantly increased the negative charge density, leading to enhanced electroosmotic flow (EOF). This enhancement resulted in ion concentration depletion at the microchannel tip and a corresponding decrease in ionic current and ECL intensity. The ECL intensity exhibited a linear dependence on the logarithm of HCHO concentration ranging from 1 pg mL-1 to 100 ng mL-1, with a detection limit of 0.26 pg mL-1(S/N = 3). The biosensor demonstrated high selectivity, successfully detecting HCHO in shrimp samples. The performance of the bioinspired sensor was confirmed through comparation with existing methods, showcasing its superior sensitivity and reliability. The bioinspired sensor provides robust technical support for HCHO detection, crucial for food safety monitoring. Additionally, the innovative combination of bionics and microchannel-based ECL technology broadens the application range of ECL sensors, marking a significant advancement in the field.
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Pomacea canaliculata, an invasive species native to South America, is recognized for its broad geographic distribution and adaptability to a variety of ecological conditions. The details concerning the evolution and adaptation of P. canaliculate remain unclear due to a lack of whole-genome resequencing data. We examined 173 P. canaliculata genomes representing 17 geographic populations in East and Southeast Asia. Interestingly, P. canaliculata showed a higher level of genetic diversity than other mollusks, and our analysis suggested that the dispersal of P. canaliculata could have been driven by climate changes and human activities. Notably, we identified a set of genes associated with low temperature adaptation, including Csde1, a cold shock protein coding gene. Further RNA sequencing analysis and reverse transcription quantitative polymerase chain reaction experiments demonstrated the gene's dynamic pattern and biological functions during cold exposure. Moreover, both positive selection and balancing selection are likely to have contributed to the rapid environmental adaptation of P. canaliculata populations. In particular, genes associated with energy metabolism and stress response were undergoing positive selection, while a large number of immune-related genes showed strong signatures of balancing selection. Our study has advanced our understanding of the evolution of P. canaliculata and has provided a valuable resource concerning an invasive species.
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Adaptação Fisiológica , Espécies Introduzidas , Caramujos , Sequenciamento Completo do Genoma , Animais , Caramujos/genética , Adaptação Fisiológica/genética , Evolução Molecular , Ásia , Variação Genética , Seleção Genética , Filogenia , Evolução BiológicaRESUMO
Combined the electrostatic interaction of the negatively charged gold nanorods (AuNRs) (as acceptor) and Ru(bpy)32+ (as donor), an electrochemiluminescence resonance energy transfer (ECL-RET) sensor was constructed and applied for the detection of organophosphorus pesticides (OPs). Negatively charged AuNRs were synthesized by modifying AuNRs with polystyrene sulfonate (PSS) firstly, which can bind to Ru(bpy)32+ through electrostatic interaction so that the luminophore was absorbed by the acceptor, the resonance energy transfer occurred and only low ECL signal had been detected. Thiocholine can be produced by the hydrolysis process of acetylthiocholine (ATCh) with the help of acetylcholinesterase (AChE), which can bond with PSS-modified AuNRs (PSS-AuNRs) through gold-sulfur interaction, this caused the releasing of the adsorbed Ru(bpy)32+ into the solution and resulting in the restoration of the ECL intensity. However, the activity of AChE was inhibited by OPs, and the recovery process of the ECL signal was thus suppressed as well. In this study, chlorpyrifos was chosen as model target, the results indicated that the correlation between the ECL intensity and the logarithm of chlorpyrifos concentration showed remarkable linearity across 1 ng/mL to 1 mg/mL, achieving a detection limit of 0.51 ng/mL. The proposed system has been utilized for detecting OPs in real samples with satisfied results.
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The realization of a rechargeable zinc-air battery (ZAB) is hindered by the low intrinsic oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) activities. In this work, an abundant built-in electric field is noticed in a 1D/2D CoO/CoS2 heterostructure, triggering electron transfer from CoO to CoS2 associated with a downshifted d band center of the Co atom mitigating the strong electrochemical adsorption of *OH species on active sites; thereby, boosted OER and ORR performance are achieved. Namely, the OER specific activity of CoO/CoS2 is enhanced by 3.8- and 2.2-fold compared to the counterpart of CoO and CoS2, respectively. Furthermore, the kinetic current density of CoO/CoS2, a fingerprint of intrinsic ORR activity, is promoted by 46 and 6.6 times relative to CoO and CoS2. The rechargeable ZAB performance attains 215.6 mW cm-2, 1.6-times better than Pt/C-IrO2. Moreover, the superior performance remained for 600 h. Besides, the battery performance of the all-solid-state ZAB reaches 83.8 mW cm-2, revealing its promising application in wearable device.
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A smart window that dynamically regulates light transmittance is crucial for modern life end-users and promising for on-demand optical devices. The advent of three-dimensional (3D) photonic crystal microspheres has enriched the functions of a smart window. However, the smart window formed by polymer microspheres encounters poor mechanical strength and microstructural defects. Herein, to solve this limitation, we report the microsphere-based smart window composed of tightly packed cross-linked polymer microspheres (as a precursor) containing organic photochromic dyes, followed by compression under a high elastic state. When excited under an ultraviolet supply, our smart window showed a rapid and reversible fluorescent photoluminescence without fatigue (50 cycles). Moreover, the bulk devices with a microsphere cross-linked network structure enable excellent mechanical strength (hardness reached 0.158 GPa) and visible-light transparency. Interestingly, a QR code can be recognized under visible light exposure but not under ultraviolet light exposure because of photoluminescence of the smart window. Our method generally provided a paradigm for various amorphous polymers, which can be regarded as a simple and effective approach to build a versatile strategy to introduce an ideal marketplace with economic and community benefits.
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High entropy alloy nanoparticles encapsulated into nitrogen-doped carbon nanotubes show superior bifunctionality for the ORR and OER, evidenced by a battery performance of 214 mW cm-2, sustained for 200 h.
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As regulatory standards for per- and polyfluoroalkyl substances (PFAS) become increasingly stringent, innovative water treatment technologies are urgently demanded for effective PFAS removal. Reported sorbents often exhibit limited affinity for PFAS and are frequently hindered by competitive background substances. Recently, fluorinated sorbents (abbreviated as fluorosorbents) have emerged as a potent solution by leveraging fluorine-fluorine (F···F) interactions to enhance selectivity and efficiency in PFAS removal. This review delves into the designs and applications of fluorosorbents, emphasizing how F···F interactions improve PFAS binding affinity. Specifically, the existence of F···F interactions results in removal efficiencies orders of magnitude higher than other counterpart sorbents, particularly under competitive conditions. Furthermore, we provide a detailed analysis of the fundamental principles underlying F···F interactions and elucidate their synergistic effects with other sorption forces, which contribute to the enhanced efficacy and selectivity. Subsequently, we examine various fluorosorbents and their synthesis and fluorination techniques, underscore the importance of accurately characterizing F···F interactions through advanced analytical methods, and emphasize the significance of this interaction in developing selective sorbents. Finally, we discuss challenges and opportunities associated with employing advanced techniques to guide the design of selective sorbents and advocate for further research in the development of sustainable and cost-effective treatment technologies leveraging F···F interactions.
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The lenticel is a channel-like structure that facilitates oxygen, carbon dioxide, and water vapor exchange on secondary growth tissue, such as a tree stem. Although the structure of lenticel has been described, there is limited understanding regarding the impact of this secondary structure on secondary growth as well as the cellular and metabolic processes underlying its formation. The study reveals the essential role of the lenticel in the process of tree secondary growth and the cellular and metabolic processes that take place during its formation. Under the stomata, lenticel development occurs when cells divide and differentiate into a structure of disconnected cells with air spaces between them. During lenticel formation, specific metabolic pathways and wax biosynthesis are activated. The SERK (somatic embryogenesis receptor kinase) gene controls lenticel density, and serk1serk3serk5 triple mutants enhance lenticel initiation. The findings shed light on the cellular and metabolic processes involved in lenticel formation, laying the groundwork for further mechanistic elucidation of their development, function, and genetic regulation in trees.
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The faradaic efficiency of Bi2WO6 is 62.0% at -0.3 V vs. RHE, an improvement of 1.4- and 1.8-times relative to Bi2O3 and WO3 for the nitrate reduction reaction. In addition, the catalysis occurring on Bi2WO6 follows the pathway: *NO3-*NO2-*NO-*NOH-*HNOH-*H2NOH-*NH3, as verified by operando Raman spectroscopy and theoretical calculations.
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1,1,3-Polyfunctionalized cyclobutane derivatives have been synthesized from sulfur ylides and bicyclo[1.1.0]butanes (BCBs). This protocol operates under mild reaction conditions without the need for catalysts, generally producing moderate to good yields of syn-addition derivatives with structural diversity. An unexpected intramolecular rearrangement mechanism has also been proposed.
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Homogeneous electrochemiluminescence (ECL) has gained attention for its simplicity and stability. However, false positives due to solution background interference pose a challenge. To address this, magnetic ECL nanoparticles (Fe3O4@Ru@SiO2 NPs) were synthesized, offering easy modification, magnetic separation, and stable luminescence. These were utilized in an ECL sensor for miRNA-155 (miR-155) detection, with locked DNAzyme and substrate chain (mDNA) modified on their surface. The poor conductivity of long-chain DNA significantly impacts the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs, resulting in weaker ECL signals. Upon target presence, unlocked DNAzyme catalyzes mDNA cleavage, leading to shortened DNA chains and reduced density. In contrast, the presence of short-chain DNA has minimal impact on the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs. Simultaneously, the material surface's electronegativity decreases, weakening the electrostatic repulsion with the negatively charged electrode, resulting in the system detecting stronger ECL signals. This sensor enables homogeneous ECL detection while mitigating solution background interference through magnetic separation. Within a range of 100 fM to 10 nM, the sensor exhibits a linear relationship between ECL intensity and target concentration, with a 26.91 fM detection limit. It demonstrates high accuracy in clinical sample detection, holding significant potential for clinical diagnostics. Future integration with innovative detection strategies may further enhance sensitivity and specificity in biosensing applications.
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DNA , Técnicas Eletroquímicas , Medições Luminescentes , MicroRNAs , Dióxido de Silício , MicroRNAs/análise , Técnicas Eletroquímicas/métodos , DNA/química , Dióxido de Silício/química , Humanos , Técnicas Biossensoriais/métodos , Propriedades de Superfície , DNA Catalítico/química , DNA Catalítico/metabolismo , Nanopartículas de Magnetita/química , Limite de Detecção , Rutênio/químicaRESUMO
BACKGROUND: Depression is a serious and complex mental disease that has attracted worldwide attention because of its high incidence rate, high disability rate and high mortality. Excitotoxicity is one of the most important mechanisms involved in the pathophysiological process of depression. In our previous studies, n-butanol extract from maize roots was found to have good neuroprotective effects due to its antioxidative activity. However, the antidepressive effective constituents, efficacy in vivo and mechanism of action of maize root extracts have not been determined. PURPOSE: This study aimed to determine the main active neuroprotective compound in maize root extract and investigate its antidepressant effects and possible underlying mechanism in vitro and in vivo. METHODS: Sixteen extracts were isolated and purified from maize roots. The active components of the most active extracts of maize roots (hereafter referred to as EM 2) were identified using UF-HPLC-QTOF/MS. In vitro cell models of NMDA-induced excitotoxicity in SH-SY5Y cells were used to analyze the anti-excitatory activity of the extracts. The MTT assay and Annexin V-FITC/PI Apoptosis Detection were used to evaluate cell viability. Several network pharmacological strategies have been employed to investigate the potential mechanism of action of EM 2. The effects of EM 2 on depressive-like behaviors were evaluated in CUMS mice. Changes in the levels of related proteins were detected via western blotting. RESULTS: Among the 16 extracts extracted by n-butanol, EM 2 was determined to be the most active extract against NMDA-induced excitotoxicity by n-butanol extraction. Meanwhile, seventeen compounds were further identified as the main active components of EM 2. Mechanistically, EM 2 inhibited NMDA-induced excitatory injury in SH-SY5Y cells and alleviated the depressive-like behaviors of CUMS mice by suppressing NR2B and subsequently mediating the downstream CREB/TRKB/BDNF, PI3K/Akt and MAPK pathways, as well as the Nrf2/HO-1 antioxidant signaling pathway. CONCLUSION: The study indicated that EM 2 could potentially be developed as a potential therapeutic candidate to cure depression in NMDA-induced excitatory damage.
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Antidepressivos , Apoptose , Depressão , Fármacos Neuroprotetores , Extratos Vegetais , Raízes de Plantas , Zea mays , Animais , Antidepressivos/farmacologia , Zea mays/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Raízes de Plantas/química , Humanos , Camundongos , Depressão/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Introduction: We have developed a risk-scoring model using gene expression levels related to mitotic spindle assembly (MSA) to predict the prognosis of liver cancer. Methods and results: Initially, we identified 470 genes related to MSA from public databases. Subsequently, through analysis of sequencing data from liver cancer patient samples in online databases, we identified 7 genes suitable for constructing the risk-scoring model. We validated the predictive accuracy and clinical utility of the model. Through drug sensitivity analysis, we identified SAC3D1 as a gene sensitive to the most common anti-tumor drugs among these 7 genes. We propose SAC3D1 as a significant target for future clinical treatment. Furthermore, we conducted in vivo and in vitro experiments to validate the relevance of SAC3D1 to MSA and found its significant impact on the PI3K/Akt signaling pathway and spindle function. Conclusion: Our research introduces a novel risk-scoring model that accurately predicts liver cancer prognosis. Additionally, our findings suggest SAC3D1 as a promising therapeutic target for hepatocellular carcinoma, potentially revealing new mechanisms underlying liver cancer development.
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Prediabetes is an early phase before diabetes. Diabetes and dietary inflammation are two crucial factors that are strongly associated with cardiovascular diseases (CVDs). Dietary interventions slowed the progression of diabetes and CVD. However, the associations between CVDs and dietary inflammation in different stages of pathoglycaemia have not been investigated. To explore the effect of a proinflammatory diet on CVD incidence at different stages of diabetes, NHANES (2001-2018) data were collected and analysed. A total of 3137 CVD patients with a comparable non-CVD group (n = 3137) were enrolled after propensity score matching (PSM) analysis. These patients were subsequently categorized into three subgroups: those with diabetes (n = 3043), those with prediabetes (n = 1099) and those with normoglycemia (n = 2132). The DII (Dietary inflammatory index) is a risk factor for CVD, both in overall individuals and in each subgroup of population-based information. In diabetic individuals, the odds ratios (ORs) (95% CIs) of CVD incidence for the DII were 1.10 (1.05, 1.15) and 1.08 (1.03, 1.13) according to the crude and adjusted models, respectively. For individuals with prediabetes, the ORs (95% CIs) of CVD risk for DII were 1.05 (0.97, 1.14) and 1.11 (1.01, 1.22) according to the crude and adjusted models, respectively. After adjusting for population-based information and hypertension status, the DII appeared to have the highest OR for individuals with prediabetes, and no significant association was found between the DII score and CVD risk in the normoglycemia group. Moreover, the OR of CVD for DII in the uncontrolled diabetes group was 1.06 (0.98, 1.16)*. These results suggest that the DII is more closely associated with the risk of CVDs in prediabetic and diabetic populations, and we should pay more attention to diet control before a person develops diabetes to prevent CVD progression.
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Doenças Cardiovasculares , Dieta , Inflamação , Inquéritos Nutricionais , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/complicações , Masculino , Feminino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Pessoa de Meia-Idade , Inflamação/epidemiologia , Prevalência , Adulto , Fatores de Risco , Incidência , Idoso , Diabetes Mellitus/epidemiologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To explore the efficacy and safety of 5% lidocaine-medicated plaster (LMP) in patients with trigeminal neuralgia (TN). BACKGROUND: TN is an excruciatingly painful type of neuropathic facial pain. Anti-epileptics are the first-line treatment for TN; however, these oral drugs alone sometimes fail to achieve satisfactory analgesic effects. Two retrospective studies have shown that LMP can be an effective and safe treatment option for some patients with TN. No other high-quality clinical studies have explored the effect and safety of LMP in patients with TN. METHODS: The PATCH trial is an enriched enrollment with randomized withdrawal, double-blind, vehicle-controlled, parallel-group trial performed at five study centers. Eligible patients with TN received LMP during a 3-week initial open-label phase. Patients who met the response criteria entered the double-blind treatment phase and were randomly assigned for treatment with either LMP (LMP group) or vehicle patches (control group) at a 1:1 ratio. Patients who met the criteria for treatment failure were withdrawn from the double-blind treatment phase, and treatment was continued in the remaining patients for up to 28 days. The primary outcome was the number of treatment failures. The secondary endpoints were the time to loss of therapeutic response (LTR) in the double-blind phase and the weekly mean pain severity in both the open-label phase and the double-blind phase of the study. RESULTS: The first patient was enrolled in this study on May 1, 2021, and the enrollment of the last patient was completed on August 26, 2022. A total of 307 patients were initially screened, 226 (74.0%) of whom entered the open-label phase. Of the 226 respondents, 124 (55.0%) were randomized to the double-blind phase. In the double-blind phase, 62 patients were assigned to the LMP group, and 62 were assigned to the control group. For the primary endpoint, 16 (26.0%) patients with LMP and 36 (58.0%) patients with vehicle patches met the treatment failure criteria during the double-blind phase (relative risk, 0.48; 95% confidence interval [CI], 0.31 to 0.75; p < 0.001). The survival curve of the LTR showed that the LTR of LMP was significantly longer than that of the vehicle patches (hazard ratio, 0.275; 95% CI, 0.15 to 0.50; log-rank p < 0.001). LMP also significantly reduced the weekly mean pain severity in the double-blind phase of the study (p = 0.007). CONCLUSIONS: LMP produced partial relief of pain symptoms in some patients with TN. For responders, LMP may be used as an add-on therapy in a multidrug treatment protocol.
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This study aims to investigate the causal relationship between primary Sjögren's syndrome (SS) and multiple sclerosis (MS) using a two-sample Mendelian randomization (MR) analysis to provide insights into their common mechanisms and implications for therapeutic strategies. We utilized data from Genome-Wide Association Studies (GWAS) for primary SS (1,290 cases and 213,145 controls) and MS (4,888 cases and 10,395 controls), restricted to European ancestry. Instrumental variables (IVs) were selected based on genetic variants associated with primary SS. The primary MR method was Inverse Variance Weighted (IVW), supplemented by MR Egger, Weighted Median, Simple Mode, and Weighted Mode algorithms to assess the bidirectional causal relationships between MS and primary SS. Sensitivity analyses, including MR-PRESSO and leave-one-out analysis, were conducted to ensure the robustness of our findings. After excluding SNPs with pleiotropic effects, 42 and 5 SNPs were identified as robust IVs for primary SS and MS, respectively. Our analysis revealed a significant protective effect of MS on primary SS, with IVW showing an OR of 0.896 (95% CI: 0.841-0.954, P = 0.001). No significant heterogeneity or horizontal pleiotropy was detected, supporting the reliability of the results. Our findings suggest a potential protective effect of MS against primary SS, indicating a negative causal association between these two autoimmune diseases. This adds valuable genetic evidence to the understanding of the complex interplay between primary SS and MS, offering new avenues for research and therapeutic interventions.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Esclerose Múltipla , Polimorfismo de Nucleotídeo Único , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/genética , Esclerose Múltipla/genética , Predisposição Genética para Doença/genéticaRESUMO
Carbon nanomaterials rarely exist in isolation in the natural environment, and their combined effects cannot be ignored. Multi-walled carbon nanotubes (MWCNTs) have shown tremendous potential applications in diverse fields, including pollution remediation, biomedicine, energy, and smart agriculture. However, the combined toxicities of MWCNTs and pesticides on non-target organisms, particularly amphibians, are often overlooked. Fluxapyroxad (FLX), a significant succinate dehydrogenase inhibitor fungicide, has been extensively utilized for the protection of food and cash crops and control of fungi. This raises the possibility of coexistence of MWCNTs and FLX. The objective of this study was to explore the individual and combined toxic effects of FLX and MWCNTs on the early life stages of Xenopus laevis. Embryos were exposed to varying concentrations of FLX (0, 5, and 50 µg/L) either alone or in combination with MWCNTs (100 µg/L) for a duration of 17 days. The findings indicated that co-exposure to FLX and MWCNTs worsened the inhibition of growth, liver damage, and dysregulation of enzymatic activity in tadpoles. Liver transcriptomic analysis further revealed that the presence of MWCNTs exacerbated the disturbances in glucose and lipid metabolism caused by FLX. Additionally, the combined exposure groups exhibited amplified alterations in the composition and function of the gut microflora. Our study suggests that it is imperative to pay greater attention to the agricultural applications, management and ecological risks of MWCNTs in the future, considering MWCNTs may significantly enhance the toxicity of FLX.