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BACKGROUND: Proteome-wide Mendelian randomization studies have been increasingly utilized to identify potential drug targets for diseases. We aimed to identify potential therapeutic targets for migraine and its subtypes through the application of Mendelian randomization and co-localization analysis methods. METHODS: We utilized cis-protein quantitative trait loci data for 1378 plasma proteins available from two studies with 7213 individuals and 35,559 individuals, respectively. Summary data for migraine and its subtypes were obtained from a genetic study involving up to 1,339,303 individuals. Proteins that passed both the discovery and validation Mendelian randomization analysis, sensitivity analysis, heterogeneity test, and pleiotropy test, were associated with ≥2 outcomes, and received strong support from co-localization analysis (PP.H4.abf ≥0.80) and were classified as tier 1 proteins. RESULTS: We identified three tier 1 proteins (LRP11, ITIH1, and ADGRF5), whose genes have not been previously identified as causal genes for migraine in genetic studies. LRP11 was significantly associated with the risk of any migraine (OR [odds ratio] = 0.968, 95% CI [confidence interval] = 0.955-0.981, p = 1.27 × 10-6) and significantly/suggestively associated with three migraine subtypes. ITIH1 was significantly associated with the risk of any migraine (OR = 1.044, 95% CI = 1.024-1.065, p = 1.08 × 10-5) and migraine with visual disturbances. ADGRF5 was significantly associated with the risk of any migraine (OR = 0.964, 95% CI = 0.946-0.982, p = 8.74 × 10-5) and suggestively associated with migraine with aura. The effects of LRP11 and ADGRF5 were further replicated using cerebrospinal fluid protein data. Apart from ADGRF5, there was no evidence of potential adverse consequences when modulating the plasma levels. We also identified another four proteins (PLCG1, ARHGAP25, CHGA, and MANBA) with no potential adverse consequences when modulating the plasma levels, and their genes were not reported by previous genetic studies. CONCLUSIONS: We found compelling evidence for two proteins and suggestive evidence for four proteins that could be promising targets for migraine treatment without significant adverse consequences. The corresponding genes were not reported in previous genetic studies. Future studies are needed to confirm the causal role of these proteins and explore the underlying mechanisms.
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Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Migrañosos , Proteoma , Humanos , Estudio de Asociación del Genoma Completo/métodos , Trastornos Migrañosos/genética , Trastornos Migrañosos/sangre , Trastornos Migrañosos/líquido cefalorraquídeo , Trastornos Migrañosos/diagnóstico , Proteoma/metabolismo , Sitios de Carácter Cuantitativo , Femenino , Masculino , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido SimpleRESUMEN
Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and patterning. FGFs and their receptors (FGFR) are crucial for adult tissue repair processes. Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage, bone loss, muscle reduction, and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis (OA), intervertebral disc degeneration (IVDD), osteoporosis (OP), and sarcopenia. In OA and IVDD pathologies specifically, FGF1, FGF2, FGF8, FGF9, FGF18, FGF21, and FGF23 regulate the synthesis, catabolism, and ossification of cartilage tissue. Additionally, the dysregulation of FGFR expression (FGFR1 and FGFR3) promotes the pathological process of cartilage degradation. In OP and sarcopenia, endocrine-derived FGFs (FGF19, FGF21, and FGF23) modulate bone mineral synthesis and decomposition as well as muscle tissues. FGF2 and other FGFs also exert regulatory roles. A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration. Moreover, an increasing number of potential targets within the FGF signaling have been identified, such as FGF9, FGF18, and FGF23. However, it should be noted that most of these discoveries are still in the experimental stage, and further studies are needed before clinical application can be considered. Presently, this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases. Besides, current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.
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Factores de Crecimiento de Fibroblastos , Osteoartritis , Transducción de Señal , Humanos , Factores de Crecimiento de Fibroblastos/fisiología , Factores de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal/fisiología , Osteoartritis/fisiopatología , Factor-23 de Crecimiento de Fibroblastos , Degeneración del Disco Intervertebral/fisiopatología , Osteoporosis/fisiopatología , Osteoporosis/etiología , Sarcopenia/fisiopatología , Envejecimiento/fisiología , AnimalesRESUMEN
BACKGROUND: To investigate the relationship between egg consumption and mortality in individuals with pre-existing coronary heart disease or stroke. METHODS: This study utilized data from the National Health and Nutrition Examination Survey conducted between 1999 and 2018. Egg consumption was evaluated through 24 h dietary recalls at baseline. Mortality status was tracked until December 31, 2019. Survey-weighted Cox proportional hazards models were utilized. RESULTS: The study involved 3,975 participants aged 20 years or older with a median follow-up of 89.00 months. A total of 1,675 individuals died during follow-up. Compared to individuals who did not consume eggs, the consumption of 0-50 g/day (hazard ratio [HR] = 1.033, 95% confidence interval [CI] =0.878-1.214) was not found to have a significant association with all-cause mortality. However, consuming 50-100 g/day (HR = 1.281, 95% CI = 1.004-1.635) and >100 g/day (HR = 1.312, 95% CI =1.036-1.661) exhibited a significant association with an increased risk of all-cause mortality. We identified a non-liner relationship between egg consumption and cardiovascular mortality, where the risk was found to be lowest at an intake of about 50 g/day. For individuals consuming more than 50 g/day, each additional 50 g increment in egg consumption was significantly linked to an elevated risk of cardiovascular mortality (HR = 1.276, 95% CI = 1.009-1.614). CONCLUSION: In U.S. adults with pre-existing cardiovascular disease, a significant positive association was found between consuming over 50 g of eggs per day and the risk of mortality, highlighting the importance of moderate intake.
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Enfermedad Coronaria , Huevos , Encuestas Nutricionales , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Estados Unidos/epidemiología , Persona de Mediana Edad , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/epidemiología , Adulto , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/epidemiología , Anciano , Estudios de Cohortes , Dieta/estadística & datos numéricos , Factores de Riesgo , Modelos de Riesgos ProporcionalesRESUMEN
This study investigated the correlation of newly identified inflammatory and insulin resistance indices with cerebral amyloid angiopathy (CAA), and explored their potential to differentiate CAA from hypertensive arteriopathy (HA). We retrospectively analyzed 514 consecutive patients with cerebral small vessel disease (CSVD)-related haemorrhage, comparing the differences in novel inflammatory and insulin resistance indices between patients with CAA and HA. Univariate regression, LASSO and multivariate regression were used to screen variables and construct a classification diagnosis nomogram. Additionally, these biomarkers were explored in patients with mixed haemorrhagic CSVD. Inflammatory indices were higher in CAA patients, whereas insulin resistance indices were higher in HA patients. Further analysis identified neutrophil-to-lymphocyte ratio (NLR, OR 1.17, 95% CI 1.07-1.30, P < 0.001), and triglyceride-glucose index (TyG, OR = 0.56, 95% CI 0.36-0.83, P = 0.005) as independent factors for CAA. Therefore, we constructed a CAA prediction nomogram without haemorrhagic imaging markers. The nomogram yielded an area under the curve (AUC) of 0.811 (95% CI 0.764-0.865) in the training set and 0.830 (95% CI 0.718-0.887) in the test set, indicating an ability to identify high-risk CAA patients. These results show that CSVD patients can be phenotyped using novel inflammatory and insulin resistance indices, potentially allowing identification of high-risk CAA patients without haemorrhagic imaging markers.
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Biomarcadores , Angiopatía Amiloide Cerebral , Inflamación , Resistencia a la Insulina , Humanos , Masculino , Femenino , Angiopatía Amiloide Cerebral/patología , Anciano , Estudios Retrospectivos , Biomarcadores/sangre , Inflamación/patología , Persona de Mediana Edad , Neutrófilos/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/patología , Enfermedades de los Pequeños Vasos Cerebrales/sangre , Nomogramas , Linfocitos/metabolismo , Triglicéridos/sangreRESUMEN
Mechanical stress can directly activate chemical reactions by reducing the reaction energy barrier. A possible mechanism of such mechanochemical activation is structural deformation of the reactant species. However, the effect of deformation on the reaction energetics is unclear, especially, for shear stress-driven reactions. Here, we investigated shear stress-driven oligomerization reactions of cyclohexene on silica using a combination of reactive molecular dynamics simulations and ball-on-flat tribometer experiments. Both simulations and experiments captured an exponential increase in reaction yield with shear stress. Elemental analysis of ball-on-flat reaction products revealed the presence of oxygen in the polymers, a trend corroborated by the simulations, highlighting the critical role of surface oxygen atoms in oligomerization reactions. Structural analysis of the reacting molecules in simulations indicated the reactants were deformed just before a reaction occurred. Quantitative evidence of shear-induced deformation was established by comparing bond lengths in cyclohexene molecules in equilibrium and prior to reactions. Nudged elastic band calculations showed that the deformation had a small effect on the transition state energy but notably increased the reactant state energy, ultimately leading to a reduction in the energy barrier. Finally, a quantitative relationship was developed between molecular deformation and energy barrier reduction by mechanical stress.
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Previous researches have primarily emphasized the deleterious impacts of NH4+ on anaerobic granular sludge due to its biotoxicity. Despite this, the role of NH4+ as a monovalent cation in leaching multivalent Ca2+, thereby hindering granule formation and undermining its stability, remains underappreciated. This study investigated the potential of NH4+ to leach Ca2+ from anaerobic granular sludges. The results indicated that a shock loading of NH4+ at a concentration of 900 mg/L caused a Ca2+ leaching of 57.1 mg/L at pH 7.0. In an acidified environment (pH 5.0), the shock loading resulted in a Ca2+ release of 127.3 mg/L, a magnitude 5.24 times greater than the control group. The leaching process modestly affected granular sludge activity and size but markedly compromised granular strength due to calcium loss. Subsequent to the NH4+ shock, the granular strength manifested a significant reduction, as evidenced by a 15-fold increase in protein release from the granules compared to the intact ones. Additionally, NH4+ shock altered the calcium partitioning within the granular sludge, resulting in a decrease in residual calcium and a concomitant increase in bound calcium, further affecting granular strength. This study underscores the overlooked significant phenomenon of NH4+ shock-leaching Ca2+ in anaerobic granular sludge, which warrants significant attention given to its rapid and deleterious effects on granular strength and the shift in calcium state.
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Degenerative musculoskeletal diseases are structural and functional failures of the musculoskeletal system, including osteoarthritis, osteoporosis, intervertebral disc degeneration (IVDD), and sarcopenia. As the global population ages, degenerative musculoskeletal diseases are becoming more prevalent. However, the pathogenesis of degenerative musculoskeletal diseases is not fully understood. Previous studies have revealed that endoplasmic reticulum (ER) stress is a stress response that occurs when impairment of the protein folding capacity of the ER leads to the accumulation of misfolded or unfolded proteins in the ER, contributing to degenerative musculoskeletal diseases. By affecting cartilage degeneration, synovitis, meniscal lesion, subchondral bone remodeling of osteoarthritis, bone remodeling and angiogenesis of osteoporosis, nucleus pulposus degeneration, annulus fibrosus rupture, cartilaginous endplate degeneration of IVDD, and sarcopenia, ER stress is involved in the pathogenesis of degenerative musculoskeletal diseases. Preclinical studies have found that regulation of ER stress can delay the progression of multiple degenerative musculoskeletal diseases. These pilot studies provide foundations for further evaluation of the feasibility, efficacy, and safety of ER stress modulators in the treatment of musculoskeletal degenerative diseases in clinical trials. In this review, we have integrated up-to-date research findings of ER stress into the pathogenesis of degenerative musculoskeletal diseases. In a future perspective, we have also discussed possible directions of ER stress in the investigation of degenerative musculoskeletal disease, potential therapeutic strategies for degenerative musculoskeletal diseases using ER stress modulators, as well as underlying challenges and obstacles in bench-to-beside research.
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Degeneración del Disco Intervertebral , Osteoartritis , Osteoporosis , Sarcopenia , Humanos , Estrés del Retículo Endoplásmico/fisiología , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patologíaRESUMEN
Cerebral small vessel disease (CSVD) causes 20%-25% of stroke and contributes to 45% of dementia cases worldwide. However, since its early symptoms are inconclusive in addition to the complexity of the pathological basis, there is a rather limited effective therapies and interventions. Recently, accumulating evidence suggested that various brain-waste-clearance dysfunctions are closely related to the pathogenesis and prognosis of CSVD, and after a comprehensive and systematic review we classified them into two broad categories: trans-barrier transport and lymphatic drainage. The former includes blood brain barrier and blood-cerebrospinal fluid barrier, and the latter, glymphatic-meningeal lymphatic system and intramural periarterial drainage pathway. We summarized the concepts and potential mechanisms of these clearance systems, proposing a relatively complete framework for elucidating their interactions with CSVD. In addition, we also discussed recent advances in therapeutic strategies targeting clearance dysfunction, which may be an important area for future CSVD research.
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Enfermedades de los Pequeños Vasos Cerebrales , Sistema Glinfático , Accidente Cerebrovascular , Humanos , Barrera Hematoencefálica/metabolismo , Meninges , Encéfalo/metabolismoRESUMEN
Liquid biopsy is an emergent test method for the diagnosis and prognosis in the clinic. Joint fluid, also known as synovial fluid, contains a variety of bioactive constituents that can be selectively detected and further evaluated in a convenient fashion. Therefore, synovial fluid analysis functions as a specific form of liquid biopsy and plays a vital role in numerous joint diseases. In spite of the component analysis of aspirated synovial fluid beingconsidered as the gold standard for diagnosis of joint infections, biopsy of joint fluid benefits the initial diagnosis and long-term prognosis of degenerative, inflammatory, autoimmune, traumatic, congenital, and even neoplastic joint diseases. The convenience and accuracy for disease evaluation are significantly elevated as a result of the combination of synovial fluid analysis and other novel clinical technologies. In this review, we shed light on the latent role of synovial fluid in the diagnosis and prognosis of articular diseases and proposed future prospects for relevant research in this field.
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Artropatías , Infecciones Relacionadas con Prótesis , Humanos , Líquido Sinovial , Pronóstico , Biomarcadores/análisis , BiopsiaRESUMEN
Background: Cerebral small vessel disease (CSVD) is common in the elderly population. Neutrophil gelatinase-associated lipocalin (NGAL) is closely related to cardiovascular and cerebrovascular diseases. NGAL causes pathological changes, such as damage to the vascular endothelium, by causing inflammation, which results in other related diseases. The purpose of this study was to investigate whether serum NGAL levels could predict disease severity in patients with CSVD. Methods: The patients with CSVD who visited the Department of Neurology at the First Affiliated Hospital of Zhengzhou University between January 2018 and June 2022 were prospectively included. The total CSVD burden score was calculated using whole-brain magnetic resonance imaging (MRI), and the patients were divided into a mild group (total CSVD burden score < 2 points) and a severe group (total CSVD burden score ≥ 2 points). Age, sex, height, smoking and alcohol consumption history, medical history, and serological results of patients were collected to perform the univariate analysis. Multivariate logistic regression was used to analyze the risk factors that affect CSVD severity. The multiple linear regression method was used to analyze which individual CSVD markers (periventricular white matter hyperintensities, deep white matter hyperintensities, lacune, and cerebral microbleed) play a role in the association between total CSVD burden score and NGAL. Results: A total of 427 patients with CSVD (140 in the mild group and 287 in the severe group) were included in the study. A multivariate logistic regression analysis showed that the following factors were significantly associated with CSVD severity: male sex [odds ratio(OR), 1.912; 95% confidence interval (CI), 1.150-3.179], age (OR, 1.046; 95% CI, 1.022-1.070), history of cerebrovascular disease (OR, 3.050; 95% CI, 1.764-5.274), serum NGAL level (OR, 1.005; 95% CI, 1.002-1.008), and diabetes (OR, 2.593; 95% CI, 1.424-4.722). A multivariate linear regression shows that periventricular white matter hyperintensities and cerebral microbleed are associated with serum NGAL concentrations (P < 0.05). Conclusion: Serum NGAL level is closely related to CSVD severity and is a risk factor for the burden of CSVD brain damage. Serum NGAL has high specificity in reflecting the severity of CSVD.
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Plankton are widely distributed in the aquatic environment and serve as an indicator of water quality. Monitoring the spatiotemporal variation in plankton is an efficient approach to forewarning environmental risks. However, conventional microscopy counting is time-consuming and laborious, hindering the application of plankton statistics for environmental monitoring. In this work, an automated video-oriented plankton tracking workflow (AVPTW) based on deep learning is proposed for continuous monitoring of living plankton abundance in aquatic environments. With automatic video acquisition, background calibration, detection, tracking, correction, and statistics, various types of moving zooplankton and phytoplankton were counted at a time scale. The accuracy of AVPTW was validated with conventional counting via microscopy. Since AVPTW is only sensitive to mobile plankton, the temperature- and wastewater-discharge-induced plankton population variations were monitored online, demonstrating the sensitivity of AVPTW to environmental changes. The robustness of AVPTW was also confirmed with natural water samples from a contaminated river and an uncontaminated lake. Notably, automated workflows are essential for generating large amounts of data, which are a prerequisite for available data set construction and subsequent data mining. Furthermore, data-driven approaches based on deep learning pave a novel way for long-term online environmental monitoring and elucidating the correlation underlying environmental indicators. This work provides a replicable paradigm to combine imaging devices with deep-learning algorithms for environmental monitoring.
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Aprendizaje Profundo , Plancton , Animales , Fitoplancton , Zooplancton , Calidad del Agua , Monitoreo del Ambiente , EcosistemaRESUMEN
OBJECTIVES: To determine whether dual-energy CT (DECT) can be used to accurately and reliably detect anterior cruciate ligament (ACL) rupture. MATERIALS AND METHODS: Participants with unilateral ACL rupture were prospectively enrolled, and the bilateral knees were scanned by DECT. A tissue-specific mapping algorithm was applied to improve the visualization of the ACLs. The 80-keV CT value, mixed-keV CT value, electron density (Rho), and effective atomic number (Zeff) were measured to quantitatively differentiate torn ACLs from normal ACLs. MRI and arthroscopy served as the reference standards. RESULTS: Fifty-one participants (mean age, 27.0 ± 8.7 years; 31 men) were enrolled. Intact and torn ACLs were explicitly differentiated on color-coded DECT images. The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs (p < 0.001). The optimal cutoff values were an 80-keV CT value of 61.8 HU, a mixed-keV CT value of 60.9 HU, and a Rho of 51.8 HU, with AUCs of 98.0% (95% CI: 97.0-98.9%), 99.2% (95% CI: 98.6-99.7%), and 99.8% (95% CI: 99.6-100.0%), respectively. Overall, DECT had almost perfect reliability and validity in detecting ACL integrity (sensitivity = 97.1% [95% CI: 88.1-99.8%]; specificity = 98.0% [95% CI: 89.5-99.9%]; PPV = 98.0% [95% CI: 93.0-99.8%]; NPV = 97.1% [95% CI: 91.7-99.4%]; accuracy = 97.5% [95% CI: 94.3-99.2%]). There was no evidence of a difference between MRI and DECT in the diagnostic performance (p > 0.99). CONCLUSION: DECT has excellent diagnostic accuracy and reliability in qualitatively and quantitatively diagnosing ACL rupture. CLINICAL RELEVANCE STATEMENT: DECT could validly and reliably diagnose ACL rupture using both qualitative and quantitative methods, which may become a promising substitute for MRI to evaluate the integrity of injured ACLs and the maturity of postoperative ACL autografts. KEY POINTS: ⢠On color-coded DECT images, an uncolored ACL was a reliable sign for qualitatively diagnosing ACL rupture. ⢠The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs, which contributed to the quantitative diagnosis of ACL rupture. ⢠DECT had an almost perfect diagnostic performance for ACL rupture, and diagnostic capability was comparable between MRI and DECT.
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Lesiones del Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Masculino , Humanos , Adolescente , Adulto Joven , Adulto , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/cirugía , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Tomografía Computarizada por Rayos X/métodosRESUMEN
Mixotrophic denitrification processes have a great potential in nitrogen removal in biological wastewater treatment processes. However, so far, few studies have focused on the mixotrophic denitrification system using Fe(II) as an exclusively assisted electron donors and the underlying mechanisms in such a process remain unclear. Furthermore, the mechanisms by which microorganisms cover carbon, nitrogen, phosphorus and iron in an iron-assisted mixotrophic system remain unrevealed. In this work, we explore the feasibility of using Fe(II) as an assisted electron donor for enhancing simultaneous nitrogen and phosphorus removal via long-term reactor operation and batch tests. The results show that Fe(II) could provide electrons for efficient nitrate reduction and that biological reactions played a predominant role in these systems. In these systems Thermomonas, a strain of nitrate-reduction Fe(II)-oxidation bacterium, was enriched and accounted for a maximum abundance of 60.2%. These findings indicate a great potential of the Fe(II)-assisted mixotrophic denitrification system for practical use as an efficient simultaneous nitrogen and phosphorus removal process.
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BACKGROUND: Necroptosis of macrophages is a necessary element in reinforcing intrapulmonary inflammation during acute lung injury (ALI). However, the molecular mechanism that sparks macrophage necroptosis is still unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor expressed broadly on monocytes/macrophages. The influence of TREM-1 on the destiny of macrophages in ALI requires further investigation. METHODS: TREM-1 decoy receptor LR12 was used to evaluate whether the TREM-1 activation induced necroptosis of macrophages in lipopolysaccharide (LPS)-induced ALI in mice. Then we used an agonist anti-TREM-1 Ab (Mab1187) to activate TREM-1 in vitro. Macrophages were treated with GSK872 (a RIPK3 inhibitor), Mdivi-1 (a DRP1 inhibitor), or Rapamycin (an mTOR inhibitor) to investigate whether TREM-1 could induce necroptosis in macrophages, and the mechanism of this process. RESULTS: We first observed that the blockade of TREM-1 attenuated alveolar macrophage (AlvMs) necroptosis in mice with LPS-induced ALI. In vitro, TREM-1 activation induced necroptosis of macrophages. mTOR has been previously linked to macrophage polarization and migration. We discovered that mTOR had a previously unrecognized function in modulating TREM-1-mediated mitochondrial fission, mitophagy, and necroptosis. Moreover, TREM-1 activation promoted DRP1Ser616 phosphorylation through mTOR signaling, which in turn caused surplus mitochondrial fission-mediated necroptosis of macrophages, consequently exacerbating ALI. CONCLUSION: In this study, we reported that TREM-1 acted as a necroptotic stimulus of AlvMs, fueling inflammation and aggravating ALI. We also provided compelling evidence suggesting that mTOR-dependent mitochondrial fission is the underpinning of TREM-1-triggered necroptosis and inflammation. Therefore, regulation of necroptosis by targeting TREM-1 may provide a new therapeutic target for ALI in the future.
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Lesión Pulmonar Aguda , Lipopolisacáridos , Animales , Ratones , Receptor Activador Expresado en Células Mieloides 1 , Lipopolisacáridos/farmacología , Dinámicas Mitocondriales , Necroptosis , Serina-Treonina Quinasas TOR , Macrófagos , InflamaciónRESUMEN
The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.
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Terapia por Acupuntura , Desplazamiento del Disco Intervertebral , Meridianos , Humanos , Medicina Tradicional China , Desplazamiento del Disco Intervertebral/terapia , Terapia por Acupuntura/métodos , Procedimientos Quirúrgicos Vasculares , Puntos de AcupunturaRESUMEN
BACKGROUND: Severe knee valgus/varus or complex multiplanar deformities are common in clinic. If not corrected in time, cartilage wear will be aggravated and initiate the osteoarthritis due to lower limb malalignment. Internal fixation is unable to correct severe complex deformities, especially when combined with lower limb discrepancy (LLD). Based on the self-designed digital six-axis external fixator Q spatial fixator (QSF), which can correct complex multiplanar deformities without changing structures, accuracy of correction can be improved significantly. METHODS: This retrospective study included 24 patients who suffered from complex knee deformity with LLD treated by QSF and internal fixation at our institution from January 2018 to February 2021. All patients had a closing wedge distal femoral osteotomy with internal fixation for immediate correction and high tibia osteotomy with QSF fixation for postoperative progressive correction. Data of correction prescriptions were computed by software from postoperative CT scans. RESULTS: Mean discrepancy length of operative side was 2.39 ± 1.04 cm (range 0.9-4.4 cm) preoperatively. The mean difference of lower limb was 0.32 ± 0.13 cm (range 0.11-0.58 cm) postoperatively. The length of limb correction had significant difference (p < 0.05). The mean MAD and HKA decreased significantly (p < 0.05), and the mean MPTA and LDFA increased significantly (p < 0.05). There were significant increase (p < 0.05) in the AKSS-O, AKSS-F and Tegner Activity Score. The lower limb alignment was corrected (p < 0.05). The mean time of removing external fixator was 112.8 ± 17.9 days (range 83-147 days). CONCLUSIONS: Complex knee deformity with LLD can be treated by six-axis external fixator with internal fixation without total knee arthroplasty. Lower limb malalignment and discrepancy can be corrected precisely and effectively by this approach.
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Fijadores Externos , Fijación de Fractura , Humanos , Estudios Retrospectivos , Articulación de la Rodilla/cirugía , Extremidad Inferior , Tibia/diagnóstico por imagen , Tibia/cirugíaRESUMEN
PURPOSE: To evaluate the extent of tunnel widening after anterior cruciate ligament reconstruction (ACLR) using the all-inside technique and to establish its correlation with patient-reported clinical outcomes and femoral graft bending angle (GBA). METHODS: Tunnel widening was evaluated using computed tomography (CT)-based three-dimensional (3D) models, and the femoral GBA was directly measured on CT images using the Picture Archiving and Communication System (PACS) software. Clinical follow-up was routine procedure, and patient-reported clinical outcomes mainly included International Knee Documentation Committee (IKDC), Lysholm, and Knee Injury and Osteoarthritis Outcome Scores (KOOS) scores, and subjective knee stability assessment. RESULTS: Fifty-two patients received standard all-inside ACLR, with a median follow-up of 6 months. Reconstructed anterior cruciate ligaments (ACLs) were scanned during the first 3 days and 6 months after surgery. On both the femoral and tibial sides, bone tunnels were most significantly enlarged at the articular aperture segment; the femoral tunnel was 9.2 ± 1.3 mm postoperatively and was significantly enlarged by 32% to a mean tunnel diameter of 12.1 ± 2.0 mm at 6 months after surgery. Moreover, the extent of tunnel enlargement gradually decreased as the measured levels approached those of the bone cortex. The femoral tunnel center was shifted into the anterior and distal direction, and the tibial tunnel center was shifted into the posterior and lateral direction. Additionally, the mean femoral GBA was 105.9° ± 8.1° at the 6-month follow-up. Tunnel enlargement and GBA were not significantly correlated with patient-reported outcomes. CONCLUSIONS: Femoral and tibial tunnels were significantly greater and eccentrically shifted at the 6-month follow-up after all-side ACLR. However, the extent of tunnel widening does not markedly affect the short-term clinical outcomes. Meanwhile, the femoral GBA was not significantly correlated with femoral tunnel widening or patient-reported outcomes. Although the tunnel widening following all-inside ACLR was not associated with clinical outcomes, it potentially caused difficulties in revision ACLR. LEVEL OF EVIDENCE: Level IV.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Humanos , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Ligamento Cruzado Anterior/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Tibia/diagnóstico por imagen , Tibia/cirugía , Fémur/diagnóstico por imagen , Fémur/cirugía , Tomografía Computarizada por Rayos X/métodos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Hipertrofia/cirugíaRESUMEN
OBJECTIVE: GGC repeat expansions in the human-specific NOTCH2NLC gene have been reported as the cause of neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of cognitive impairment in NIID and cerebral small vessel disease (CSVD), both diseases have white matter hyperintensity on T2-fluid-attenuated inversion recovery sequences of brain MRI, and white matter hyperintensity is a primary neuroimaging marker of CSVD on MRI. Therefore, we hypothesised that the GGC repeat expansions might also contribute to CSVD. To further investigate the relationship between NOTCH2NLC GGC repeat expansions and CSVD, we performed a genetic analysis of 814 patients with the disease. METHODS: We performed a comprehensive GGC repeat expansion screening in NOTCH2NLC from 814 patients with sporadic CSVD. Their Fazekas score was greater than or equal to 3 points. Repeat-primed PCR and fluorescence amplicon length analyses were performed to identify GGC repeat expansions, and whole-exome sequencing was used to detect any pathogenic mutation in previously reported genes associated with CSVD. RESULTS: We identified nine (1.11%) patients with pathogenic GGC repeat expansions ranging from 41 to 98 repeats. The minor allele frequency of expanded GGC repeats in NOTCH2NLC was 0.55%. CONCLUSION: Our findings suggest that intermediate-length and longer-length GGC repeat expansions in NOTCH2NLC are associated with sporadic CSVD. This provides new thinking for studying the pathogenesis of CSVD.
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Enfermedades Neurodegenerativas , Humanos , Cuerpos de Inclusión Intranucleares/genética , Cuerpos de Inclusión Intranucleares/patología , Mutación , Imagen por Resonancia MagnéticaRESUMEN
Floccules are another major form of microbial aggregates in aerobic granular sludge systems. Previous studies mainly attributed the persistence of floccules to their relatively faster nutrient uptake and higher growth rate over aerobic granules; however, they failed to unravel the underlying mechanism of the long-term coexistence of these two aggregates. In this work, the existence and function of the floccules in an aerobic granule-dominated sequencing batch reactor were investigated from the view of quorum sensing (QS) and quorum quenching (QQ). The results showed that though the floccules were closely associated with the granules in terms of similar community structures (including the QS- and QQ-related ones), they exhibited a relatively higher QQ-related activity but a lower QS-related activity. A compatible proportion of floccules might be helpful to maintain the QS-related activity and keep the granules stable. In addition, the structure difference was demonstrated to diversify the QS- and QQ-related activities of the floccules and the aerobic granules. These findings could broaden our understanding of the interactions between the coexistent floccules and granules in aerobic granule-dominated systems and would be instructive for the development of the aerobic granular sludge process.
Asunto(s)
Percepción de Quorum , Aguas del Alcantarillado , Reactores Biológicos , Transporte Biológico , AerobiosisRESUMEN
Osteoarthritis (OA) is the most common joint disease, affecting hundreds of millions of people globally, which leads to a high cost of treatment and further medical care and an apparent decrease in patient prognosis. The recent view of OA pathogenesis is that increased vascularity, bone remodeling, and disordered turnover are influenced by multivariate risk factors, such as age, obesity, and overloading. The view also reveals the gap between the development of these processes and early stage risk factors. This review presents the latest research on OA-related signaling pathways and analyzes the potential roles of perlecan, a typical component of the well-known protective structure against osteoarthritic pericellular matrix (PCM). Based on the experimental results observed in end-stage OA models, we summarized and analyzed the role of perlecan in the development of OA. In normal cartilage, it plays a protective role by maintaining the integrin of PCM and sequesters growth factors. Second, perlecan in cartilage is required to not only activate vascular epithelium growth factor receptor (VEGFR) signaling of endothelial cells for vascular invasion and catabolic autophagy, but also for different signaling pathways for the catabolic and anabolic actions of chondrocytes. Finally, perlecan may participate in pain sensitization pathways.