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BACKGROUND: Insular low-grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). PURPOSE: This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. STUDY TYPE: Retrospective. POPULATION: 42 patients (mean age 40.26 ± 10.21 years, 25 male) with insular LGGs. FIELD STRENGTH/SEQUENCE: Imaging was performed using 3.0 Tesla MRI, incorporating T1-weighted magnetization-prepared rapid gradient-echo, T2-weighted space dark-fluid with spin echo (SE), and diffusional kurtosis imaging (DKI) with gradient echo sequences, all integrated with echo planar imaging. ASSESSMENT: Shape metrics of the CST, including span, irregularity, radius, and irregularity of end regions (RER and IER, respectively), were compared between the affected and healthy hemispheres. Total end region radius (TRER) was determined as the sum of RER 1 and RER 2. The relationships between shape metrics and postoperative short-term (4 weeks) and long-term (>8 weeks) motor disturbances assessing by British Medical Research Council grading system, was analyzed using multivariable regression models. STATISTICAL TESTING: Paired t-tests compared CST metrics between hemispheres. Logistic regression identified associations between these metrics and motor disturbances. The models were developed using all available data and there was no independent validation dataset. Significance was set at P < 0.05. RESULTS: Short-term motor disturbance risk was significantly related to TRER (OR = 199.57). Long-term risk significantly correlated with IER 1 (OR = 59.84), confirmed as a significant marker with an AUC of 0.78. Furthermore, the CST on the affected side significantly had the greater irregularity, larger TRER and RER 1, and smaller span compared to the healthy side. DATA CONCLUSION: Preoperative evaluation of TRER and IER 1 metrics in the CST may serve as a tool for assessing the risk of postoperative motor complications in insular LGG patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.
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OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.
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Neoplasias Encefálicas , Glioma , Humanos , Metilación de ADN , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/tratamiento farmacológico , Enzimas Reparadoras del ADN/genética , O(6)-Metilguanina-ADN Metiltransferasa/genética , Metilasas de Modificación del ADN/genética , Regiones Promotoras Genéticas , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Proteínas Supresoras de Tumor/genéticaRESUMEN
Radix ginseng and Schisandra chinensis have been extensively documented in traditional Chinese medicine (TCM) for their potential efficacy in treating dementia. However, the precise mechanism of their therapeutic effects remains to be fully elucidated. In this study, air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) and network pharmacology are used to investigate the pharmacodynamics and mechanism underlying the herbal combination consisting of Radix ginseng-Schisandra chinensis (RS) in a rodent model for Alzheimer's disease (AD). Brain histopathological findings suggested that RS attenuates hippocampal damage in AD mice, making this combination a potential AD treatment. Twenty-eight biomarkers were identified by spatial metabolomics analysis, which are intricately linked to neuroinflammation, neurotransmitter imbalance, energy deficiency, oxidative stress, and aberrant fatty acid metabolism in AD. The total extract of RS (TE) affected 22 of these biomarkers, with the small molecule components of RS (SN) significantly influencing 19 and the large molecule components of RS (PR) impacting 14. Nine small molecule components are likely to dominate the pharmacodynamics of RS. We constructed a target interaction network based on the corresponding bioactivities that revealed relationships amongst 11 key biomarkers, 8 active ingredients and 12 critical targets. This research illustrates the immense potential of spatial metabolomics and network pharmacology in the study of TCM, revealing the targets and mechanisms underlying herbal formulas.
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Enfermedad de Alzheimer , Medicamentos Herbarios Chinos , Metabolómica , Farmacología en Red , Panax , Schisandra , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Metabolómica/métodos , Panax/química , Schisandra/química , Farmacología en Red/métodos , Ratones , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/farmacocinética , Masculino , Biomarcadores/metabolismo , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
As a widely distributed plant in Northeast China, Carex meyeriana Kunth (CMK) is generally considered to have antibacterial properties; however, there is a lack of scientific evidence for this. Therefore, we investigated the chemical composition of CMK extract and its effect against C. albicans. A total of 105 compounds were identified in the alcohol extracts of CMK by UPLC-Q-TOF-MS. Most were flavonoids, with Luteolin being the most represented. Among them, 19 compounds are found in the C. albicans lysates. After treatment with CMK ethanol extract, a significant reduction in the number of C. albicans colonies was observed in a vaginal douche solution from day 5 (p < 0.05). Furthermore, the CMK extract can reduce the number of C. albicans spores. The levels of IL-4, IL-6, IL-10, IL-1ß, and TNF-α in vaginal tissues all exhibited a significant decrease (p < 0.05) compared to those in the model group as determined by ELISA. The results of HE staining showed that CMK extract can eliminate vaginal mucosa inflammation. CMK adjusts the vaginal mucosa cells by targeting twenty-six different metabolites and five specific metabolic pathways in order to effectively eliminate inflammation. Simultaneously, the CMK regulates twenty-three types of metabolites and six metabolic pathways against C. albicans infection. So, CMK strongly inhibits the growth of C. albicans and significantly reduces vaginal inflammation, making it a promising candidate for treating C. albicans infection.
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Antifúngicos , Candida albicans , Extractos Vegetales , Vagina , Candida albicans/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Femenino , Antifúngicos/farmacología , Antifúngicos/química , Vagina/microbiología , Vagina/efectos de los fármacos , Animales , Citocinas/metabolismo , Humanos , RatonesRESUMEN
Cell membrane chromatography (CMC) has been widely recognized as a highly efficient technique for in vitro screening of active compounds. Nevertheless, conventional CMC approaches suffer from a restricted repertoire of cell membrane proteins, making them susceptible to oversaturation. Moreover, the binding mechanism between silica gel and proteins primarily relies on intermolecular hydrogen bonding, which is inherently unstable and somewhat hampers the advancement of CMC. Consequently, this investigation aimed to establish a novel CMC column that could augment protein loading, enhance detection throughput, and bolster binding affinity through the introduction of covalent bonding with proteins. This study utilizes polydopamine (PDA)-coated silica gel, which is formed through the self-polymerization of dopamine (DA), as the carrier for the CMC column filler. The objective is to construct the HK-2/SiO2-PDA/CMC model to screen potential therapeutic drugs for gout. To compare the quantity and characteristics of Human Kidney-2 (HK-2) cell membrane proteins immobilized on SiO2-PDA and silica gel, the proteins were immobilized on both surfaces. The results indicate that SiO2-PDA has a notably greater affinity for membrane proteins compared to silica gel, resulting in a significant improvement in detection efficiency. Furthermore, a screening method utilizing HK-2/SiO2-PDA/CMC was utilized to identify seven potential anti-gout compounds derived from Plantago asiatica L. (PAL). The effectiveness of these compounds was further validated using an in vitro cell model of uric acid (UA) reabsorption. In conclusion, this study successfully developed and implemented a novel CMC filler, which has practical implications in the field.
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Gota , Indoles , Plantago , Polímeros , Humanos , Gel de Sílice , Dióxido de Silicio , Membrana Celular , Proteínas de la Membrana , Riñón , Cromatografía , ExcipientesRESUMEN
Based on aggregation-induced emission (AIE) and twisted intramolecular charge transfer (TICT) mechanisms, a fluorescent probe SWJT-12 for the detection of ClO- was designed by using the CîN bond as a reactive group. This synthesized probe can react with ClO- in a high aqueous phase, and it shows a large Stokes shift (144 nm) and low biological toxicity. Its limit of detection was calculated to be 0.28 µM. Furthermore, SWJT-12 was successfully used for ratiometric imaging of the exogenous hypochlorite anion in living cells.
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Ácido Hipocloroso , Imagen Óptica , Humanos , Células HeLa , Microscopía Fluorescente , Colorantes Fluorescentes/químicaRESUMEN
A series of lathyrane-type Euphorbia diterpene derivatives featured 3R configuration (H-3ß) were synthesized from natural rich Euphorbia factor L3via modified Mitsunobu reaction based on configuration inversion strategy. The antiproliferation activity and MDR reversal ability of the lathyrane derivatives were evaluated, and the most synthesized compounds showed moderate or strong potencies. Among them, diterpenes 21 (IC50 values of 2.6, 5.2 and 13.1 µM, respectively) and 25 (IC50 values of 5.5, 8.6 and 1.3 µM, respectively) presented the strong cytotoxicity against MCF-7, 4 T1 and HepG2 cells. Meanwhile, derivative 25 exhibited excellent MDR reversal ability with the reversal fold of 16.1 higher than that of verapamil. The cellular thermal shift assay and molecular docking proved direct engagement of diterpene 25 to ABCB1, suggesting 25 could be a promising MDR modulator. Furthermore, the preliminary SARs of these diterpenes were also discussed.
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Antineoplásicos , Diterpenos , Euphorbia , Humanos , Línea Celular Tumoral , Diterpenos/síntesis química , Diterpenos/farmacología , Euphorbia/química , Células Hep G2 , Simulación del Acoplamiento Molecular , Estructura Molecular , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacologíaRESUMEN
BACKGROUND: Balance training is the first choice of treatment for chronic ankle instability (CAI). However, there is a lack of research on the effects of balance training in CAI with generalized joint hypermobility (GJH). This study is to compare the outcomes of balance training in CAI patients with and without GJH. METHODS: Forty CAI patients were assigned into the GJH group (Beighton ≥ 4, 20) and non-GJH group (Beighton < 4, 20) and they received same 3-month supervised balance training. Repeated measure ANOVA and independent t test were used to analyze self-reported questionnaires (Foot and ankle ability measure, FAAM), the number of patients experiencing ankle sprain, isokinetic muscle strength and postural control tests (Star excursion balance test, SEBT and Balance errors system, BES) before training, post-training immediately, and post-training 3 months, respectively. RESULTS: At baseline, no differences were found between groups with except for GJH group having poorer SEBT in the posteromedial direction (83.6 ± 10.1 vs 92.8 ± 12.3, %) and in the posterolateral direction (84.7 ± 11.7 vs 95.7 ± 8.7, %). Following the balance training, GJH group demonstrated lower re-sprain ratio (immediately after training, 11.1% vs 23.5%, 3 month after training, 16.7% vs 29.4%) than non-GJH group, as well as greater FAAM-S score, plantarflexion strength and dorsiflexion strength at post-training immediately and 3 months, and both groups improved similarly in the FAAM-A score, muscle strength and balance control (SEBT in the posterior-lateral and posterior-medial directions, and BES scores) compared with baseline. CONCLUSIONS: CAI patients with GJH gained equally even better postural stability and muscle strength after the balance training than the non-GJH patients. Balance training could still be an effective treatment for CAI patients with GJH before considering surgery. TRIAL REGISTRATION: ChiCTR1900023999, June 21st, 2019.
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Tobillo , Inestabilidad de la Articulación , Humanos , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/terapia , Estudios Prospectivos , Rango del Movimiento Articular/fisiología , Enfermedad Crónica , Articulación del Tobillo , Equilibrio Postural/fisiologíaRESUMEN
Herein, we report that α,ß-unsaturated ketones could be obtained by palladium-catalyzed ring-opening of mono-substituted cyclopropyl ketones efficiently and systematically. (E)-1-Arylbut-2-en-1-ones were generated from aryl cyclopropyl ketones stereoselectively in yields of 23-89% by the Pd(OAc)2/PCy3 catalytic system. The reaction exhibited stereoselectivity (only E products were found) and was suitable for both phenyl and heteroaryl cyclopropyl ketones.
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Cetonas , Paladio , Catálisis , Estructura MolecularRESUMEN
Andrographolide(ADE) has been demonstrated to inhibit tumor growth through direct cytotoxicity on tumor cells. However, its potential activity on tumor microenvironment (TME) remains unclear. Tumor-associated macrophages (TAMs), composed mainly of M2 macrophages, are the key cells that create an immunosuppressive TME by secretion of cytokines, thus enhancing tumor progression. Re-polarized subpopulations of macrophages may represent vital new therapeutic alternatives. Our previous studies showed that ADE possessed anti-metastasis and anoikis-sensitization effects. Here, we demonstrated that ADE significantly suppressed M2-like polarization and enhanced M1-like polarization of macrophages. Moreover, ADE inhibited the migration of M2 and tube formation in HUVECs under M2 stimulation. In vivo studies showed that ADE restrained the growth of MDA-MB-231 and HCC1806 human breast tumor xenografts and 4T-1 mammary gland tumors through TAMs. Wnt5a/ß-catenin pathway and MMPs were particularly associated with ADE's regulatory mechanisms to M2 according to RNA-seq and bioinformatics analysis. Moreoverï¼ western blot also verified the expressions of these proteins were declined with ADE exposure. Among the cytokines released by M2, PDGF-AA and CCL2 were reduced. Our current findings for the first time elucidated that ADE could modulate macrophage polarization and function through Wnt5a signaling pathway, thereby playing its role in inhibition of triple-negative breast cancer.
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Neoplasias de la Mama , Diterpenos , Vía de Señalización Wnt , Femenino , Humanos , beta Catenina , Neoplasias de la Mama/tratamiento farmacológico , Microambiente Tumoral , Macrófagos Asociados a Tumores , Diterpenos/farmacología , Células Endoteliales de la Vena Umbilical Humana , Células MDA-MB-231 , AnimalesRESUMEN
PURPOSE: To compare the clinical outcomes, rate of return to sports, postural control, and muscle strength between the arthroscopic and open modified Broström procedure for chronic lateral ankle instability (CLAI) patients. METHODS: From September 2018 to April 2019, 70 patients diagnosed with CLAI were prospectively included with arthroscopic modified Broström procedure (n = 36) and open modified Broström procedure (n = 34). They were evaluated at five time points (preoperation and 3 months, 6 months, 1 year and 2 years postoperatively). The main results examined the rate of return to sports, American Orthopaedic Foot and Ankle Society Score (AOFAS), Foot and Ankle Ability Measure (FAAM), visual analogue scale (VAS), centre of pressure (COP) excursion velocity, time to boundary (TTB), plantar pressure, isokinetic muscle strength and complications. RESULTS: Compared with the open group, the arthroscopic group demonstrated a significantly shorter period of return to the preinjury sport (13.2 ± 2.4 weeks vs. 18.7 ± 3.1 weeks, P = 0.023) and a higher early sport ratio (80.6 vs. 61.8%, P = 0.011) combined with better FAAM sports and AOFAS at 3 months and 6 months postoperatively and VAS at 3 months postoperatively. In addition, better anterior-posterior postural control stability, less time to peak force under lateral hindfoot and better dorsiflexion strength were shown in the arthroscopic group at 6 months postoperatively. No significant difference was found in clinical scores, posture control or muscle strength at the 1- or 2-year follow-up between the two groups. CONCLUSIONS: Shorter period and higher rates of return to sport activities and better clinical scores, posture control and muscle strength were achieved in the arthroscopic group at 6 months postoperatively, and no clinical differences were found between arthroscopic and open modified Broström procedure 1 year or 2 years postoperatively. Arthroscopic modified Broström procedure is a reliable procedure for CLAI injuries with the demand for fast exercise recovery. CLINICAL REGISTRATION: ChiCTR1900023999. LEVEL OF EVIDENCE: II.
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Inestabilidad de la Articulación , Ligamentos Laterales del Tobillo , Tobillo , Articulación del Tobillo/cirugía , Artroscopía/métodos , Humanos , Inestabilidad de la Articulación/cirugía , Ligamentos Laterales del Tobillo/cirugía , Estudios Retrospectivos , Volver al DeporteRESUMEN
PURPOSE: To compare the mid- to long-term clinical and radiological outcomes of the confluent L-shaped tunnel technique with the Y-graft technique for anatomic lateral ankle ligament reconstruction. METHODS: This retrospective study involved 41 patients who underwent lateral ankle ligament reconstruction between 2013 and 2018. Based on the tunnel direction and tendon fixation method at the fibula side, patients were divided into two groups, with 17 patients in the L-shaped tunnel group and 24 patients in the Y-graft group. The American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) pain score, Tegner score, and Karlsson score were evaluated and compared preoperatively and at follow-up. Anterior talar translation and talar tilt at stress radiographs, postoperative sprain recurrence, range of motion (ROM) restriction, sensory disturbance, etc., were also collected and compared. RESULTS: The mean follow-up times were 72 and 42 months for the L-shaped group and Y-graft group, respectively. The median VAS pain score, Tegner score, AOFAS score, Karlsson score significantly improved from a preoperative level in both groups (all with p < 0.01). No significant difference was found between the two groups regarding the changes from preoperatively to postoperatively except for the VAS pain score reduction (1.58 ± 1.58 in the L-shaped group vs. 2.53 ± 1.29 in the Y-graft group, p = 0.035). The incidence of flexion-extension ROM restriction (≥ 5°) was significantly higher in the Y-graft group (41.2%) than in the L-shaped group (12.5%) (p = 0.035). CONCLUSIONS: Both the confluent L-shaped tunnel technique and the Y-graft technique significantly improved symptoms, ankle function, and radiographic outcomes in patients with chronic lateral ankle instability (CLAI) at mid- to long-term follow-up. The confluent L-shaped tunnel technique resulted in lower rates of flexion-extension ROM restriction, while the Y-graft technique showed better VAS pain reduction. This result could provide further evidence for the surgical treatment of CLAI. LEVEL OF EVIDENCE: III.
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Inestabilidad de la Articulación , Ligamentos Laterales del Tobillo , Tobillo , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/cirugía , Humanos , Inestabilidad de la Articulación/cirugía , Ligamentos Laterales del Tobillo/cirugía , Dolor , Estudios RetrospectivosRESUMEN
Adoptive immunotherapy is a new potential method of tumour therapy, among which anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T cell), is a typical treatment agent for haematological malignancies. Previous clinical trials showed that the quality and phenotype of CAR-T cells expanded ex vivo would seriously affect the tumour treatment efficacy. Although magnetic beads are currently widely used to expand CAR-T cells, the optimal expansion steps and methods have not been completely established. In this study, the differences between CAR-T cells expanded with anti-CD3/CD28 mAb-coated beads and those expanded with cell-based aAPCs expressing CD19/CD64/CD86/CD137L/mIL-15 counter-receptors were compared. The results showed that the number of CD19-specific CAR-T cells with a 4-1BB and CD28 co-stimulatory domain was much greater with stimulation by aAPCs than that with beads. In addition, the expression of memory marker CD45RO was higher, whereas expression of exhausted molecules was lower in CAR-T cells expanded with aAPCs comparing with the beads. Both CAR-T cells showed significant targeted tumoricidal effects. The CAR-T cells stimulated with aAPCs secreted apoptosis-related cytokines. Moreover, they also possessed marked anti-tumour effect on NAMALWA xenograft mouse model. The present findings provided evidence on the safety and advantage of two expansion methods for CAR-T cells genetically modified by piggyBac transposon system.
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Antígenos CD19/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Animales , Western Blotting , Antígenos CD8/metabolismo , Línea Celular Tumoral , Electroporación , Citometría de Flujo , Humanos , Inmunoterapia Adoptiva/métodos , Células K562 , Masculino , Ratones , Ratones SCID , Plásmidos/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Traditional Chinese medicine believes that qi deficiency is important pathogenesis and syndrome of liver cancer and thus is crucial in related research. However, the effect of qi deficiency on the occurrence and development of liver cancer is still unclear. This study aimed to establish a liver cancer model of qi deficiency through the swimming exhaustion and xenograft of human hepatoma HepG2 cells. The effects of qi deficiency on the occurrence and development of liver cancer were investigated by analyzing tumor development, blood routine, histopathology, and serum metabolomics. Results showed that qi deficiency greatly affected the physiology and tumor growth of xenograft mice. Eight potential biomarkers were identified by metabolomics based on ultra-high performance liquid chromatography and tandem quadrupole time-of-flight mass spectrometry. Their main pathways were arachidonic acid metabolism, phenylalanine metabolism, purine metabolism, glycerolipid metabolism, steroid biosynthesis, sphingomyelin metabolism, and fatty acid metabolism pathway. Finally, the effects of qi deficiency on the occurrence and development of liver cancer were comprehensively analyzed, and the mechanism of this process was preliminarily clarified.
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Metabolómica , Qi , Animales , Cromatografía Líquida de Alta Presión , Células Hep G2 , Humanos , Neoplasias Hepáticas Experimentales/sangre , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Análisis Multivariante , Células Tumorales CultivadasRESUMEN
PURPOSE: Muscle strength training is a common strategy for treating chronic ankle instability (CAI), but the effectiveness decreases for mechanical ankle instability (MAI) patients with initial severe ligament injuries. The purpose of this study was to investigate the characteristics and the potential predictors of muscle strength deficit in MAI patients, with a view to proposing a more targeted muscle strength training strategy. METHODS: A total of 220 MAI patients with confirmed initial lateral ankle ligament rupture and a postinjury duration of more than 6 months were included. All patients underwent a Biodex isokinetic examination of the ankle joints of both the affected and unaffected sides. Then, the associations between the limb symmetry index (LSI) (mean peak torque of the injury side divided by that of the healthy side) and the patients' sex, body mass index, postinjury duration, presence of intra-articular osteochondral lesions, presence of osteophytes and ligament injury pattern (i.e., isolated anterior talofibular ligament (ATFL) injury or combined with calcaneofibular ligament injury) were analysed. RESULTS: There was significantly weaker muscle strength on the affected side than on the unaffected side in all directions (p < 0.05). The LSI in plantar flexion was significantly lower than that in dorsiflexion at 60°/s (0.87 vs 0.98, p < 0.001). A lower LSI in eversion was significantly correlated with female sex (0.82 vs 0.94, p = 0.016) and isolated ATFL injury (0.86 vs 0.95, p = 0.012). No other factors were found to be associated with muscle strength deficits. CONCLUSION: MAI patients showed significant muscle strength deficits on the affected side, especially in plantar flexion. There were greater strength deficits in eversion in females and individuals with an isolated ATFL injury. Thus, a muscle strength training programme for MAI patients was proposed that focused more on plantar flexion training and eversion training for females and those with an isolated ATFL injury.
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Traumatismos del Tobillo , Inestabilidad de la Articulación , Ligamentos Laterales del Tobillo , Tobillo , Traumatismos del Tobillo/diagnóstico , Articulación del Tobillo , Femenino , Humanos , Fuerza MuscularRESUMEN
BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (P<0.05); variants in FOXL2 and MYH6 were found in patients with isolated, sporadic ASD (P<5×10^-4). CONCLUSIONS This was the first study that demonstrated variants in FOXL2 and HYDIN associated with sporadic ASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.
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Pueblo Asiatico/genética , Defectos del Tabique Interatrial/genética , Adulto , Miosinas Cardíacas/genética , Miosinas Cardíacas/metabolismo , China , Biología Computacional/métodos , Exoma , Exones , Femenino , Proteína Forkhead Box L2/genética , Proteína Forkhead Box L2/metabolismo , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Masculino , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Mutación , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Análisis de Secuencia de ADN/métodos , Secuenciación del Exoma/métodosRESUMEN
A high-precision Complementary Metal-Oxide-Semiconductor (CMOS) temperature sensor for (−5 °C, 120 °C) temperature range is designed and analyzed in this investigation. The proposed design is featured with a temperature range selection circuit so that the thermistor linear circuit automatically switches to a corresponding calibration loop in light of the temperature range besides the analysis of the calibration method. It resolves the problem that the temperature range of a single thermistor temperature sensor is too small. Notably, the output of the proposed design also attains a high linearity. The measurement results in a thermal chamber justifying that the output voltage is 1.96 V to 4.15 V, the maximum linearity error ≤1.4%, and the worst temperature error ≤1.1 °C in the temperature range of −5 °C to 120 °C.
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BACKGROUND: Post-operative volume of subdural fluid is considered to correlate with recurrence in chronic subdural haematoma (CSDH). Information on the applications of computer-assisted volumetric analysis in patients with CSDHs is lacking. OBJECTIVE: To investigate the relationship between haematoma recurrence and longitudinal changes in subdural fluid volume using CT volumetric analysis. METHODS: Fifty-four patients harbouring 64 CSDHs were studied prospectively. The association between recurrence rate and CT findings were investigated. RESULTS: Eleven patients (20.4%) experienced post-operative recurrence. Higher pre-operative (over 120 ml) and/or pre-discharge subdural fluid volumes (over 22 ml) were significantly associated with recurrence; the probability of non-recurrence for values below these thresholds were 92.7% and 95.2%, respectively. CSDHs with larger pre-operative (over 15.1 mm) and/or residual (over 11.7 mm) widths also had significantly increased recurrence rates. Bilateral CSDHs were not found to be more likely to recur in this series. On receiver-operating characteristic curve, the areas under curve for the magnitude of changes in subdural fluid volume were greater than a single time-point measure of either width or volume of the subdural fluid cavity. CONCLUSIONS: Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the 'self-resolution' period can be used as significantly radiological predictors of recurrence.
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Craniectomía Descompresiva , Hematoma Subdural Crónico/diagnóstico por imagen , Hematoma Subdural Crónico/patología , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Hematoma Subdural Crónico/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Medición de Riesgo , Espacio Subdural/diagnóstico por imagen , Espacio Subdural/patologíaRESUMEN
UNLABELLED: OBJECTITVE: To explore the mechanism of human umbilic mesenchymal cells (HUMSCs) implantation for the treatment of diabetic foot in rats associate with vascular endothelia growth factor (VEGF) expression changes. METHODS: After diabetic foot model in rats were established by administration of streptozotozin (STZ) in intraperitoneal injection (2 weeks), ulceration in foot was induced by incision injury combined with swearing staphylococcus aureas. Then, HUMSCs were smeared on the ulceration of foot in diabetic rats. Ten days later, the densities of blood vessel and the level of VEGF expression were determined by using immunohistochemistry, RT-PCR and Western blot. RESULTS: HUMSC grafts reduced significantly the volume of ulceration in diabetic foot rats (P < 0.05). RT-PCR and Western blot showed that VEGF and its mRNA were significantly upregulated (P < 0.05). VEGF immunstaining was found in blood vessels and the densities of blood vessels in HUMSC group were increased significantly (P < 0.05). CONCLUSION: HUMSC implantation showed a positive role in promoting the recovery of the ulceration in foot with diabetic rats.
Asunto(s)
Pie Diabético/terapia , Células Madre Mesenquimatosas/citología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Diabetes Mellitus Experimental/patología , Humanos , ARN Mensajero , Ratas , Cordón Umbilical/citología , Cicatrización de HeridasRESUMEN
Fubai chrysanthemum is a kind of traditional Chinese medicine, which can be used as a common food, and is commonly used to improve and relieve visual fatigue. However, its pharmacodynamic material basis and action mechanisms in relieving visual fatigue have not been systematically studied. In this article, 11 absorbed ingredients from Fubai chrysanthemum were detected in rat plasma. Then, the target network pharmacology and KEGG pathway analysis were performed. It was found that Fubai chrysanthemum could inhibit various apoptotic cells and reduce oxidative damage of eyes by regulating the apoptosis pathway, thus alleviating visual fatigue. Further in vitro experiments showed that Fubai chrysanthemum could effectively protect against oxidation damage of adult retinal pigment epithelial cells (ARPE-19), retinal ganglion cells (RGC-5), and lens. The results of cell experiments showed that Fubai chrysanthemum could increase the cell activity, GSH content, and SOD content of ARPE-19 and RGC-5 after oxidative injury, while decreasing the IL-18 content. Similarly, in the study of lens transparency, we found that Fubai chrysanthemum could effectively alleviate the oxidative damage degree of the lens, and significantly increase the content of CAT, GSH, and SOD. The above results suggested that Fubai chrysanthemum could play an important role in alleviating visual fatigue through regulating cell apoptosis and antioxidative damage.