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1.
Front Neurol ; 15: 1376019, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38957353

RESUMEN

Introduction: Neurogenic hypertension (HTN) is a type of HTN characterized by increased activity of the sympathetic nervous system. Vascular compression is one of the pathogenic mechanisms of neurogenic HTN. Despite Jannetta's solid anatomical and physiological arguments in favor of neurogenic HTN in the 1970's, the treatment for essential HTN by microvascular decompression (MVD) still lacks established selection criteria. Therefore, the subjects selected for our center were limited to patients with primary trigeminal neuralgia (TN) and primary hemifacial spasm (HFS) of the vertebral/basilar artery (VA/BA) responsible vessel type coexisting with neurogenic HTN who underwent MVD of the brainstem to further explore possible indications for MVD in the treatment of neurogenic HTN. Methods: A retrospective analysis of 63 patients who were diagnosed with neurogenic HTN had symptoms of HFS and TN cranial nerve disease. Patients were treated at our neurosurgery department from January 2018 to January 2023. A preoperative magnetic resonance examination of the patients revealed the presence of abnormally located vascular compression in the rostral ventrolateral medulla (RVLM) and the root entry zone (REZ) of the IX and X cranial nerves (CN IX- X). Results: There was no significant difference between the two groups in terms of gender, age, course of HFS, course of TN, course of HTN, degree of HTN, or preoperative blood pressure. Based on the postoperative blood pressure levels, nine out of 63 patients were cured (14.28%), eight cases (12.70%) showed a marked effect, 16 cases (25.40%) were effective, and 30 cases were invalid (47.62%). The overall efficacy was 52.38%. However, 39 cases of combined cranial nerve disease were on the left side of the efficacy rate (66.67%) and 24 cases of combined cranial nerve disease were on the right side of the efficacy rate (29.16%). Discussion: Over the last few decades, many scholars have made pioneering progress in the clinical retrospective study of MVD for neurogenic hypertension, and our study confirms the efficacy of MVD in treating vertebral/basilar artery-type neurogenic hypertension by relieving the vascular pressure of RVLM. In the future, with the development and deepening of pathological mechanisms and clinical observational studies, MVD may become an important treatment for neurogenic hypertension by strictly grasping the surgical indications. Conclusion: MVD is an effective treatment for neurogenic HTN. Indications may include the following: left-sided TN or HFS combined with neurogenic HTN; VA/BA compression in the left RVLM and REZ areas on MRI; and blood pressure in these patients cannot be effectively controlled by drugs.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38824486

RESUMEN

Microbubble-mediated sonothrombolysis has been proven to be a non-invasive and efficient method for thrombolysis. Nevertheless, there is a potential risk that the thrombus debris generated during the dissolution of the original thrombus are too large and can lead to hazardous emboli. Using a sonothrombolysis microfluidic platform, we investigated the effects of ultrasound power, thrombolytic agent and microbubble concentration on the size of thrombus debris with the example of microbubble-mediated sonothrombolysis of arterial thrombus. Additionally, we studied the effects of ultrasound power on the size and shape of thrombus debris produced by acute and chronic arterial sonothrombolysis. In acute arterial sonothrombolysis, ultrasound power has significant effect on the size of thrombus debris and steadily increases with the increase of ultrasound power. Conversely, in chronic arterial sonothrombolysis, the size of thrombus debris is minimally affected by ultrasound power. Using the sonothrombolysis microfluidic platform, the relationship between ultrasound power and the safety of sonothrombolysis has been illustrated, and the sonothrombolysis microfluidic platform is demonstrated to be a promising tool for further studies on the process of sonothrombolysis.

3.
Nat Commun ; 15(1): 4293, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858360

RESUMEN

Membrane proteins are critical to biological processes and central to life sciences and modern medicine. However, membrane proteins are notoriously challenging to study, mainly owing to difficulties dictated by their highly hydrophobic nature. Previously, we reported QTY code, which is a simple method for designing water-soluble membrane proteins. Here, we apply QTY code to a transmembrane receptor, histidine kinase CpxA, to render it completely water-soluble. The designed CpxAQTY exhibits expected biophysical properties and highly preserved native molecular function, including the activities of (i) autokinase, (ii) phosphotransferase, (iii) phosphatase, and (iv) signaling receptor, involving a water-solubilized transmembrane domain. We probe the principles underlying the balance of structural stability and activity in the water-solubilized transmembrane domain. Computational approaches suggest that an extensive and dynamic hydrogen-bond network introduced by QTY code and its flexibility may play an important role. Our successful functional preservation further substantiates the robustness and comprehensiveness of QTY code.


Asunto(s)
Histidina Quinasa , Proteínas de la Membrana , Solubilidad , Agua , Agua/química , Agua/metabolismo , Histidina Quinasa/metabolismo , Histidina Quinasa/química , Histidina Quinasa/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Ingeniería de Proteínas , Dominios Proteicos
4.
PLoS One ; 19(6): e0306269, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38941340

RESUMEN

Thermal damage from heat sources severely affects the safety of deep mine production. Heat and mass transfer between heat sources and airflow leads to the increase of the airflow temperature (AFT), moisture content of airflow (AFMC) and relative humidity of airflow (AFRH). This study aims to quantify uncertainty contributions of the working face parameters on AFT, AFMC and AFRH and find their main contributors. The flow, geometric and physical parameters are chosen as uncertainty sources. Subsequently, Sobol indices are obtained using the point-collocation non-intrusive polynomial chaos method, denoting the sensitivity of each input parameter. It was found that the inflow wind temperature and the wind velocity are two top factors influencing AFT and AFMC, while relative humidity of inflow wind and the wind velocity are two top factors influencing AFRH. In the single factor analysis, the uncertainty contributions of the inflow wind temperature on AFT and AFMC, and relative humidity of inflow wind on AFRH can exceed 0.7, which is higher than those of the wind velocity. The geometric parameters of the working face, namely the length, width and height, and ventilation time are also significant quantities influencing AFT, AFMC and AFRH. Compared to AFT and AFMC, two other significant quantities influencing AFRH are the thermal conductivity of coal and the original temperature of the rock.


Asunto(s)
Calor , Viento , Humedad , Humanos , Minería , Conductividad Térmica , Modelos Teóricos
5.
Ann Vasc Surg ; 106: 264-272, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38815920

RESUMEN

BACKGROUND: This study was performed to summarize our experience in treating acute superior mesenteric artery embolism (SMAE) by percutaneous mechanical thrombectomy (PMT). METHODS: Between January 2023 and October 2023, 18 patients presenting with acute mesenteric ischemia were admitted to our center, including 11 cases of SMAE, 3 cases of superior mesenteric artery thrombosis, and 4 cases of superior mesenteric vein thrombosis. We retrospectively reviewed 8 patients (4 males and 4 females; range, 51-79 years; mean, 62.50 ± 9.67 years) who underwent treatment of acute SMAE using the AcoStream system. The patients had no obvious evidence of intestinal necrosis as shown by peritoneal puncture or computed tomography. Thrombectomy was performed on the superior mesenteric artery (SMA) using an 8F AcoStream thrombus aspiration system (Acotec, China). The demographics, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. RESULTS: The technical success rate was 100%. After 1-3 passes (2.38 ± 0.92) and aspiration thrombectomy, complete thrombus removal was achieved in 7 (87.50%) patients. One patient received an adjunctive catheter-directed thrombolysis due to partial thrombus removal. Thrombolysis was conducted for 2 days, resulting in complete resolution of the thrombus. The other 7 patients did not receive adjunctive endovascular intervention due to complete thrombus removal and no residual stenosis. No distal embolization or device-related complications were noted during the procedure. After the procedure, sufficient clinical improvement was seen in 6 patients within 1-2 days. Two patients showed no significant improvement of their symptoms. Laparotomy was performed on day 1 and day 2 after thrombectomy in patients 3 and 7, respectively. Intestinal necrosis was diagnosed operatively and intestinal resection was performed. All patients were discharged 6-15 days (9.50 ± 3.07) after admission without perioperative complication or death. The mean follow-up period was 5.00 ± 3.30 months (range, 1-10 months), and the follow-up rate was 100%. During the follow-up, all patients remained symptom-free. Computed tomography angiography images showed good flow in the trunk and branches of the SMA in all patients. CONCLUSIONS: PMT using the AcoStream system is a minimally invasive, safe, and effective technique for acute SMAE. Early application of PMT can achieve immediate revascularization of the SMA and have the potential advantage of avoiding laparotomy or reducing the extension of enterectomy, as it could theoretically restore intestinal perfusion in less time than open revascularization. If the symptoms do not improve after PMT, exploratory laparotomy should be scheduled as soon as possible. Further studies are necessary on this field to confirm these findings.

6.
Heliyon ; 10(7): e27742, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38560262

RESUMEN

Introduction: Few studies have focused on the risk factors for hidden blood loss (HBL) during cement augmentation surgery for pathologic vertebral compression fraction (PVCFs). Method: From January 2014 to December 2020, the clinical data of 169 PVCF patients (283 levels) who underwent cement augmentation were retrospectively analysed. HBL was calculated according to the linear Gross formula using the patient's average Hct during the perioperative course and PBV. Multivariate linear regression analysis was performed to evaluate the independent factors associated with HBL. Results: The mean HBL was 448.2 ± 267.2 ml, corresponding to 10.8% ± 6.2% of the patient blood volume (PBV). There were significant differences between pre- and postoperative haematocrit (Hct) (P < 0.001) and Hb (P < 0.001), and 132 patients developed anaemia postoperatively, while 79 patients had anaemia preoperatively (P < 0.001). Multivariate linear regression revealed that bone lesion quality (p = 0.028), number of PVCFs (p = 0.002), amount of bone cement (p = 0.027), bone cement leakage (p = 0.001), and percentage of vertebral height loss (VHL) (p = 0.011) were independent risk factors for HBL. Conclusion: In conclusion, patients with lytic vertebral destruction, larger amounts of bone cement, greater amounts of bone cement leakage, more PVCF(s), and greater percentages of VHL may be more prone to HBL.

7.
QRB Discov ; 5: e1, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577032

RESUMEN

Human ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins and perform diverse functions. Many of them are associated with multidrug resistance that often results in cancer treatment with poor outcomes. Here, we present the structural bioinformatics study of six human ABC membrane transporters with experimentally determined cryo-electron microscopy (CryoEM) structures including ABCB7, ABCC8, ABCD1, ABCD4, ABCG1, ABCG5, and their AlphaFold2-predicted water-soluble QTY variants. In the native structures, there are hydrophobic amino acids such as leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in the transmembrane alpha helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Therefore, these QTY variants become water soluble. We also present the superposed structures of native ABC transporters and their water-soluble QTY variants. The superposed structures show remarkable similarity with root mean square deviations between 1.064 and 3.413 Å despite significant (41.90-54.33%) changes to the protein sequence of the transmembrane domains. We also show the differences in hydrophobicity patches between the native ABC transporters and their QTY variants. We explain the rationale behind why the QTY membrane protein variants become water soluble. Our structural bioinformatics studies provide insight into the differences between the hydrophobic helices and hydrophilic helices and will likely further stimulate designs of water-soluble multispan transmembrane proteins and other aggregated proteins. The water-soluble ABC transporters may be useful as soluble antigens to generate therapeutic monoclonal antibodies for combating multidrug resistance in clinics.

8.
PLoS One ; 19(4): e0289644, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38598436

RESUMEN

Glutamate transporters play key roles in nervous physiology by modulating excitatory neurotransmitter levels, when malfunctioning, involving in a wide range of neurological and physiological disorders. However, integral transmembrane proteins including the glutamate transporters remain notoriously difficult to study, due to their localization within the cell membrane. Here we present the structural bioinformatics studies of glutamate transporters and their water-soluble variants generated through QTY-code, a protein design strategy based on systematic amino acid substitutions. These include 2 structures determined by X-ray crystallography, cryo-EM, and 6 predicted by AlphaFold2, and their predicted water-soluble QTY variants. In the native structures of glutamate transporters, transmembrane helices contain hydrophobic amino acids such as leucine (L), isoleucine (I), and phenylalanine (F). To design water-soluble variants, these hydrophobic amino acids are systematically replaced by hydrophilic amino acids, namely glutamine (Q), threonine (T) and tyrosine (Y). The QTY variants exhibited water-solubility, with four having identical isoelectric focusing points (pI) and the other four having very similar pI. We present the superposed structures of the native glutamate transporters and their water-soluble QTY variants. The superposed structures displayed remarkable similarity with RMSD 0.528Å-2.456Å, despite significant protein transmembrane sequence differences (41.1%->53.8%). Additionally, we examined the differences of hydrophobicity patches between the native glutamate transporters and their QTY variants. Upon closer inspection, we discovered multiple natural variations of L->Q, I->T, F->Y and Q->L, T->I, Y->F in these transporters. Some of these natural variations were benign and the remaining were reported in specific neurological disorders. We further investigated the characteristics of hydrophobic to hydrophilic substitutions in glutamate transporters, utilizing variant analysis and evolutionary profiling. Our structural bioinformatics studies not only provided insight into the differences between the hydrophobic helices and hydrophilic helices in the glutamate transporters, but they are also expected to stimulate further study of other water-soluble transmembrane proteins.


Asunto(s)
Sistema de Transporte de Aminoácidos X-AG , Agua , Sistema de Transporte de Aminoácidos X-AG/genética , Aminoácidos/química , Proteínas de la Membrana , Mutación , Biología Computacional , Glutamatos
9.
PLoS One ; 19(3): e0300340, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38517879

RESUMEN

Monoamine transporters including transporters for serotonin, dopamine, and norepinephrine play key roles in monoaminergic synaptic signaling, involving in the molecular etiology of a wide range of neurological and physiological disorders. Despite being crucial drug targets, the study of transmembrane proteins remains challenging due to their localization within the cell membrane. To address this, we present the structural bioinformatics studies of 7 monoamine transporters and their water-soluble variants designed using the QTY code, by systematically replacing the hydrophobic amino acids leucine (L), valine (V), isoleucine (I) and phenylalanine (F) with hydrophilic amino acids (glutamine (Q), threonine (T) and tyrosine (Y). The resulting QTY variants, despite significant protein transmembrane sequence differences (44.27%-51.85%), showed similar isoelectric points (pI) and molecular weights. While their hydrophobic surfaces significantly reduced, this change resulted in a minimal structural alteration. Quantitatively, Alphafold2 predicted QTY variant structures displayed remarkable similarity with RMSD 0.492Å-1.619Å. Accompanied by the structural similarities of substituted amino acids in the context of 1.5Å electron density maps, our study revealed multiple QTY and reverse QTY variations in genomic databases. We further analyzed their phenotypical and topological characteristics. By extending evolutionary game theory to the molecular foundations of biology, we provided insights into the evolutionary dynamics of chemically distinct alpha-helices, their usage in different chemotherapeutic applications, and open possibilities of diagnostic medicine. Our study rationalizes that QTY variants of monoamine transporters may not only become distinct tools for medical, structural, and evolutionary research, but these transporters may also emerge as contemporary therapeutic targets, providing a new approach to treatment for several conditions.


Asunto(s)
Dopamina , Serotonina , Dopamina/metabolismo , Serotonina/metabolismo , Agua/metabolismo , Proteínas de Transporte de Membrana , Aminoácidos , Norepinefrina/metabolismo , Biología Computacional , Mutación , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo
10.
Sci Rep ; 14(1): 6894, 2024 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-38519533

RESUMEN

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. However, the mechanisms underlying ESCC tumorigenesis have not been fully elucidated. Thus, we aimed to determine the key genes involved in ESCC tumorigenesis. The following bioinformatics analyses were performed: identification of differentially expressed genes (DEGs); gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis; integrated analysis of the protein-protein interaction network and Gene Expression Profiling Interactive Analysis database for validation of hub genes. Finally, western blotting and qPCR were used to explore the expression of cell division cycle 6 (CDC6) in ESCC cell lines. Immunohistochemistry analysis of ESCC samples from patients and matched clinical characteristics was used to determine the effects of CDC6. A total of 494 DEGs were identified, and functional enrichment was mainly focused on cell cycle and DNA replication. Biological pathway analysis of the hub genes was closely related to the cell cycle. We found that CDC6 was upregulated in ESCC cell lines and patient tissues and was related to the clinicopathological characteristics of ESCC. In conclusion, this study identified hub genes and crucial biological pathways related to ESCC tumorigenesis and integrated analyses indicated that CDC6 may be a novel diagnostic and therapeutic target for ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Redes Reguladoras de Genes , Perfilación de la Expresión Génica , Biología Computacional , Carcinogénesis/genética , Regulación Neoplásica de la Expresión Génica
11.
J Nat Prod ; 87(4): 924-934, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38513270

RESUMEN

A diverse array of biologically active derivatives was derived by modifying the chemically active sites of dehydroabietylamine. Herein, we describe the synthesis of a new series of C-19-arylated dehydroabietylamine derivatives using a palladium-catalyzed C(sp3)-H activation reaction. Five analogues (3b, 3d, 3h, 3n, and 4a) exhibited antibacterial activity against Escherichia coli. Compound 4a exhibited strong inhibitory activity against DNA Topo II and Topo IV. Molecular docking modeling indicated that it can bind effectively to the target through interactions with amino acid residues. The synthesized compounds were tested in vitro for their antifungal activity against six common phytopathogenic fungi. The mechanism of action of compound 4c against Rhizoctorzia solani was investigated, revealing that it disrupts the morphology of the mycelium and enhances cell membrane permeability.


Asunto(s)
Abietanos , Antibacterianos , Antifúngicos , Abietanos/farmacología , Abietanos/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Antifúngicos/farmacología , Antifúngicos/química , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular
12.
Retina ; 44(7): 1209-1216, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38359396

RESUMEN

PURPOSE: To explore the clinical value of ß-D-glucan (BDG) testing and metagenomic next-generation sequencing (mNGS) for detecting the pathogens of fungal endophthalmitis (FE). METHODS: This study included 32 cases (32 eyes) with FE and 20 cases (20 eyes) with intraocular inflammation caused by other etiologies. All patients underwent extraction of aqueous humor or vitreous fluid samples for BDG testing and mNGS. The diagnostic performance and total clinical concordance rate of BDG testing and mNGS for FE were evaluated and calculated based on the results of the clinical diagnosis. RESULTS: Among the clinically diagnosed FE, the positivity rates of BDG testing and mNGS (90.63%) were both significantly higher ( P < 0.001) than that of microbial cultures (53.13%). There was 100% consistency in pathogen identification using mNGS and culture identification for culture-positive cases. The area under the curve was 0.927 for BDG testing and 0.853 for mNGS. When the two tests were combined, sensitivity (93.75%), specificity (100.00%), and total clinical concordance rate (96.15%) were all improved, compared with the single tests. CONCLUSION: The positive rates of BDG test and mNGS were markedly higher than those of cultures in FE identification. The combination of these two tests showed improved performance when compared with individual tests.


Asunto(s)
Humor Acuoso , Endoftalmitis , Infecciones Fúngicas del Ojo , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Cuerpo Vítreo , beta-Glucanos , Humanos , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Endoftalmitis/diagnóstico , Endoftalmitis/microbiología , Masculino , Persona de Mediana Edad , Femenino , Humor Acuoso/microbiología , beta-Glucanos/análisis , Cuerpo Vítreo/microbiología , Anciano , Metagenómica/métodos , Adulto , Estudios Retrospectivos , Hongos/aislamiento & purificación , Hongos/genética , ADN de Hongos/análisis , Proteoglicanos , Anciano de 80 o más Años
13.
Comput Struct Biotechnol J ; 23: 278-286, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38173876

RESUMEN

G protein-coupled receptors (GPCRs) play a pivotal role in fundamental biological processes and disease development. GPCR isoforms, derived from alternative splicing, can exhibit distinct signaling patterns. Some highly-truncated isoforms can impact functional performance of full-length receptors, suggesting their intriguing regulatory roles. However, how these truncated isoforms interact with full-length counterparts remains largely unexplored. Here, we computationally investigated the interaction patterns of three human GPCRs from three different classes, ADORA1 (Class A), mGlu2 (Class C) and SMO (Class F) with their respective truncated isoforms because their homodimer structures have been experimentally determined, and they have truncated isoforms deposited and identified at protein level in Uniprot database. Combining the neural network-based AlphaFold2 and two physics-based protein-protein docking tools, we generated multiple complex structures and assessed the binding affinity in the context of atomistic molecular dynamics simulations. Our computational results suggested all the four studied truncated isoforms showed potent binding to their counterparts and overlapping interfaces with homodimers, indicating their strong potential to block homodimerization of their counterparts. Our study offers insights into functional significance of GPCR truncated isoforms and supports the ubiquity of their regulatory roles.

14.
Foods ; 13(2)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38254506

RESUMEN

Chlorantraniliprole (CAP) is a new type of diamide insecticide that is mainly used to control lepidopteran pests. However, it has been proven to be hazardous to nontarget organisms, and the effects of its residues need to be monitored. In this study, five hybridoma cell lines were developed that produced anti-CAP monoclonal antibodies (mAbs), of which the mAb originating from the cell line 5C5B9 showed the highest sensitivity and was used to develop a gold nanoparticle-based lateral flow immunoassay (AuNP-LFIA) for CAP. The visible limit of detection of the AuNP-LFIA was 1.25 ng/mL, and the detection results were obtained in less than 10 min. The AuNP-LFIA showed no cross-reactivity for CAP analogs, except for tetraniliprole (50%) and cyclaniliprole (5%). In the detection of spiked and blind samples, the accuracy and reliability of the AuNP-LFIA were confirmed by a comparison with spiked concentrations and verified by ultra-performance liquid chromatography-tandem mass spectrometry. Thus, this study provides the core reagents for establishing CAP immunoassays and a AuNP-LFIA for the detection of residual CAP.

15.
Proteins ; 92(2): 206-218, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37795805

RESUMEN

Therapeutic monoclonal antibodies are the most rapidly growing class of molecular medicine, and they are beneficial to the treatment of a broad spectrum of human diseases. However, the aggregation of antibodies during the process of manufacture, distribution, and storage poses significant challenges, potentially compromising efficacy and inducing adverse immune responses. We previously conceived a QTY (glutamine, threonine, tyrosine) code, a simple tool for enhancing protein water-solubility by systematically pairwise replacing hydrophobic residues L (leucine), V (valine)/I (isoleucine), and F (phenylalanine). The QTY code offers a promising alternative to traditional methods of controlling aggregation in integral transmembrane proteins. In this study, we designed variants of four antibodies applying the QTY code, changing only the ß-sheets. Through the structure-based aggregation analysis, we found that these QTY antibody variants demonstrated significantly decreased aggregation propensity compared to their wild-type counter parts. Our results of molecular dynamics simulations showed that the design by QTY code is capable of maintaining the antigen-binding affinity and structural stability. Our structural informatic and computational study suggests that the QTY code offers a significant potential in mitigating antibody aggregation.


Asunto(s)
Anticuerpos Monoclonales , Tirosina , Humanos , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/química , Tirosina/metabolismo , Simulación de Dinámica Molecular , Treonina , Biología Computacional/métodos
16.
J Chin Med Assoc ; 87(1): 126-130, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-38016115

RESUMEN

BACKGROUND: To determine the feasibility and safety of ultrasound-guided totally implantable venous access port (TIVAP) implantation via the posterior approach of the internal jugular vein (IJV). METHODS: From September 2021 to August 2022, 88 oncology patients underwent ultrasound-guided implantation of TIVAPs via the posterior approach of the IJV for the administration of chemotherapy. The catheter tip was adjusted to be positioned at the cavoatrial junction under fluoroscopic guidance. Clinical data including surgical success, success rate for the first attempt, intraoperative, and postoperative complications were all collected and analyzed. RESULTS: All patients underwent successful surgery (100%), whereby 58 were via the right IJV and 30 via the left IJV, and the success rate for the first attempt was 96.59% (85/88). The operation time was 20 to 43 minutes, with an average of 26.59 ± 6.18 minutes with no intraoperative complications. The follow-up duration ranged from 1 to 12 months (mean = 5.28 ± 3.07) and the follow-up rate was 100%. The rate of postoperative complications was 4.55% (4/88), including port-site infection in two cases, fibrin sheath formation in one case, and port flip in one case. No other complications were observed during follow-up. CONCLUSION: Ultrasound-guided TIVAP implantation via the posterior approach of the IJV is feasible, safe, and effective, with a low rate of intraoperative and postoperative complications. Not only was the curvature of the catheter device smooth, but patients were satisfied with the comfort and cosmetic appearance. Additionally, we could reduce the possible complications of pinching and kinking of the catheter by using this approach. Therefore, further large-sample, prospective, and randomized controlled trials are warranted.


Asunto(s)
Cateterismo Venoso Central , Humanos , Venas Yugulares/diagnóstico por imagen , Venas Yugulares/cirugía , Catéteres de Permanencia , Estudios Prospectivos , Complicaciones Posoperatorias , Ultrasonografía Intervencional , Estudios Retrospectivos
17.
Am Surg ; 90(4): 762-769, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37905507

RESUMEN

BACKGROUND: The aim of this study is to establish a model to predict the overall survival (OS) and stratify the risk of postoperative patients with undifferentiated sarcoma. METHODS: A total of 452 postoperative patients with undifferentiated sarcoma in the trunk and extremity from the Surveillance, Epidemiology, and End Results database were enrolled as the training cohort. We collected a group of 163 undifferentiated sarcoma patients from our center as the external validation cohort. Cox proportional hazards regression model was used to screen survival-associated factors for the construction of the nomogram. Concordance-indexes (C-indexes), calibration curves, and receiver operating characteristics (ROCs) curves were applied for the discrimination and calibration of the nomogram. The cutoff value of nomogram-based total points was applied to stratify the risk of patients. RESULTS: A nomogram was developed incorporating four independent factors: age, tumor site, eighth AJCC stage, and radiotherapy. The nomogram showed good prognostic accuracy and excellent agreement in the training and validation cohort, with C-indexes of .701 (95% confidence interval [CI]: .683-.719) and .700 (95% CI: 0.659-.741), respectively. Furthermore, we identified the best cutoff value of nomogram total points (103.2) as the predicted risk and divided the patients into a high-risk group and a low-risk group. Significant differences in OS between the two groups were indicated in the training cohort and external validation cohort, showing the appreciable clinical validity and clinical utility of the nomogram (P < .001). CONCLUSION: This nomogram provides an insightful and applicable tool for individual evaluations and the distinguishment of risk for patients with undifferentiated sarcoma.


Asunto(s)
Neoplasias Hepáticas , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Estados Unidos/epidemiología , Nomogramas , Sarcoma/cirugía , Medición de Riesgo
18.
Front Neurol ; 14: 1292958, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38073645

RESUMEN

Objective: To conduct a comprehensive search and causality study of potential modifiable risk factors for trigeminal neuralgia. To provide new ideas for subsequent treatment and management of patients with trigeminal neuralgia. Methods: Data were obtained from large GWAS databases and then analyzed by Mendelian randomization analysis. The causal relationship between 36 potentially modifiable risk factors and trigeminal neuralgia was explored based on the results of the inverse variance weighting method(IVW). p < 0.05 was considered statistically significant. Results: Years of schooling [OR (95%CI), 0.59(0.42-0.84), p = 0.003] to be a significant protective factor. Anxiety disorders [OR (95%CI), 1.62(1.05-2.48), p = 0.028], Depression [OR (95%CI), 1.53(1.03-2.28), p = 0.035] and Autoimmune [OR (95%CI), 1.16(1.01-1.32), p = 0.033] were significant risk factors. Sleep duration [OR (95%CI), 0.43(0.18-1.01), p = 0.051] was a close protective factor. Body mass index [OR (95%CI), 1.24(0.98-1.57), p = 0.077] was a close risk factor. Conclusion: Mendelian randomization analysis shows Years of schooling and Sleep duration as protective factors. Anxiety disorders, Depression, Autoimmune, and Body mass index are risk factors. This will help in the research of diagnosis, treatment, and mechanism of trigeminal neuralgia. And reduce the prevalence of trigeminal neuralgia through positive psychological and lifestyle interventions.

19.
Front Neurol ; 14: 1293056, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38130833

RESUMEN

Trigeminal neuralgia is a paroxysmal, intense electric shock-like, or knife-like, recurrent pain that affects one or more sense areas of the unilateral facial trigeminal nerve. It can be classified into two groups from an etiological standpoint: primary and secondary. The pain episodes brought on by such vascular compression are still categorized as primary trigeminal neuralgia, despite the fact that microvascular compression of the trigeminal nerve root has now been demonstrated to be the primary cause. A rare and complicated condition known as a dural arteriovenous fistula (DAVF) can irritate the Gasserian ganglion or compress the trigeminal nerve's root entry zone (REZ), leading to secondary trigeminal neuralgia (TN). At present, the treatment of DAVF-induced trigeminal neuralgia is not conclusive. This article reports a case of DAVF-induced trigeminal neuralgia cured by MVD and reviews the relevant literature.

20.
ACS Appl Mater Interfaces ; 15(48): 55447-55455, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-37975805

RESUMEN

Liquid infused surfaces (LIS) hold remarkable potential in anticoagulation. However, liquid loss of LIS in the bloodstream remains a challenge toward its clinical application. Here, micronano hierarchy structures are obtained on the titanium alloy substrate by regulating the microspheres' distribution. When the gap between the microspheres is smaller than the diameter of the red blood cell (RBC), the LIS is more stable under the blood wash and presents a better anticoagulation performance. The proper interval is found to prevent the RBCs from entering the gap and remove the liquid on the surface. The retained thickness of the liquid film is measured by the atomic force microscopy (AFM) technique. The LIS is applied on the front guide vane of an artificial heart pump and exhibits significant improvement on anticoagulation in the blood circulation in vitro for 25 h. The techniques and findings can be used to optimize the anticoagulation performance of LIS-related biomedical implant devices.


Asunto(s)
Aleaciones , Titanio , Microscopía de Fuerza Atómica , Titanio/química , Eritrocitos , Anticoagulantes/farmacología
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