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1.
Angiology ; : 3319720984592, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33401931

RESUMO

We investigated the association between plasma microRNA (miR)-204 and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus (T2DM). We consecutively enrolled 179 individuals with T2DM who underwent coronary computed tomography at Anzhen Hospital from January 2015 to September 2016. The CAC score (CACS) was expressed in Agatston units and >10 Hounsfield units were defined as CAC-positive status. Significant CAC was observed in 98 (54.7%) patients. Plasma miR-204 levels (relative expression) were significantly lower in patients with significant CAC than controls (1.001 ± 0.100 vs 0.634 ± 0.211, P < .001). Plasma miR-204 levels were also negatively correlated with the glycosylated hemoglobin A1c (HbA1c) level (r = -0.702, P < .001), CACS (r = -0.710, P < .001), and the United Kingdom Prospective Diabetes Study (UKPDS) score (r = -0.355, P < .001). After multivariate logistic analyses, plasma miR-204 levels were still significantly and independently associated with the presence of CAC (odds ratio = 0.103, CI = 0.018-0.583, P < .001) after adjustment for conventional risk factors. Receiver operating characteristic curve analysis showed that plasma miR-204 levels can predict the severity and extent of CAC, and the specificity was higher than that of the traditional risk factors UKPDS score and HbA1c. In conclusion, the downregulation of miR-204 was independently associated with CAC in patients with T2DM.

2.
Proc Natl Acad Sci U S A ; 118(3)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33402433

RESUMO

Artemisinin-resistant malaria parasites have emerged and have been spreading, posing a significant public health challenge. Antimalarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a "selective starvation" strategy by inhibiting Plasmodium falciparum hexose transporter 1 (PfHT1), the sole hexose transporter in P. falciparum, over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites. The crystal structure of hGLUT3, which shares 80% sequence similarity with hGLUT1, was resolved in complex with C3361, a moderate PfHT1-specific inhibitor, at 2.3-Å resolution. Structural comparison between the present hGLUT3-C3361 and our previously reported PfHT1-C3361 confirmed the unique inhibitor binding-induced pocket in PfHT1. We then designed small molecules to simultaneously block the orthosteric and allosteric pockets of PfHT1. Through extensive structure-activity relationship studies, the TH-PF series was identified to selectively inhibit PfHT1 over hGLUT1 and potent against multiple strains of the blood-stage P. falciparum Our findings shed light on the next-generation chemotherapeutics with a paradigm-shifting structure-based design strategy to simultaneously target the orthosteric and allosteric sites of a transporter.

3.
Clin Rheumatol ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33432451

RESUMO

To assess the efficacy and safety of interleukin (IL)-17A inhibitors in patients with ankylosing spondylitis (AS). PubMed, EMBASE, and Web of Science were searched up to 5 February 2020 for randomized controlled trials (RCTs) that assessed the efficacy and safety of IL-17A inhibitors in patients with AS. We used a meta-analytic approach to perform a random effects analysis or fixed effects analysis according to heterogeneity. Subgroup analyses between studies included medication, time to primary endpoint, and data source. Odds ratios (ORs) or mean differences (MDs) were used to assess the efficacy and safety of IL-17A inhibitors in AS. A total of ten RCTs with 2613 patients were eligible for inclusion in the analysis (six for secukinumab, two for ixekizumab, one for netakimab, and one for bimekizumab). Compared to placebo, IL-17A inhibitors improved ASAS20 response rate (OR = 2.58; p < 0.01) and ASAS40 response rate (OR = 2.80; p < 0.01), and significantly increased the risk of AEs (OR = 1.23; p = 0.03) and nasopharyngitis (OR = 1.72; p < 0.01), but not SAEs (OR = 0.87; p = 0.60). IL-17A inhibitors demonstrated better efficacy in patients with AS in several evaluation indicators. However, the safety of IL-17A inhibitors remains to be further studied in studies with larger sample size and longer follow-up times.

4.
Aging (Albany NY) ; 13(1): 1458-1472, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33472166

RESUMO

Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD). Carboxyl terminus of Hsp70-interacting protein (CHIP) is a key regulator of mitochondrial dynamics, and mutations in CHIP or deficits in its expression have been associated with various neurological diseases. This study explores the protective role of CHIP in cells and murine PD models. In SH-SY5Y cell line, overexpression of CHIP improved the cell viability and increased the ATP levels upon treatment with 1-methyl-4-phenylpyridinium (MPP+). To achieve CHIP overexpression in animal models, we intravenously injected mice with AAV/BBB, a new serotype of adeno-associated virus that features an enhanced capacity to cross the blood-brain barrier. We also generated gene knock-in mice that overexpressed CHIP in neural tissue. Our results demonstrated that CHIP overexpression in mice suppressed 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage, including movement impairments, motor coordination, and spontaneous locomotor activity, as well as loss of dopaminergic neurons. In vitro and in vivo experiments showed that overexpression of CHIP inhibited the pathological increase in Drp1 observed in the PD models, suggesting that CHIP regulates Drp1 degradation to attenuate MPP+/MPTP-induced injury. We conclude that CHIP plays a protective role in MPP+/MPTP-induced PD models. Our experiments further revealed that CHIP maintains the integrity of mitochondria.

5.
Biomed Pharmacother ; 135: 111183, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33401222

RESUMO

BACKGROUND: Our previous studies found that Pure total flavnoids from citrus (PTFC) can effectively improve non-alcoholic steatohepatitis (NASH) in mice. Here, we discuss on the mechanism of PTFC in treating NASH with focus on the regulation of the gut microbiota and bile acid metabolism. METHODS: C57BL/6 J mice were randomly divided into three groups: normal diet group (Normal), high-fat diet group (HFD) and high-fat + PTFC treatment group (PTFC). Mice in the Normal group were fed chow diet, while the other groups were fed high fat diet (HFD) for 16 weeks. In the 5th week, the mice in the PTFC group were treated with 50 mg/kg/day PTFC for an additional twelve weeks. After sacrifice, histopathology of the liver was assessed, and the gut microbial composition was analyzed by 16S rDNA gene sequencing. Bile Acid profiles in serum were determined by ultraperformance liquid chromatography (UPLC-MS/MS). RESULTS: PTFC intervention significantly attenuated HFD-induced NASH symptoms compared with the HFD group in mice. 16S rDNA sequencing showed that PTFC treatment increased the phylogenetic diversity of the HFD-induced microbiota dysbiosis. PTFC intervention significantly increased the relative abundances of Bacteroidaceae and Christensenellaceae. Furthermore, PTFC reduced the content of toxic bile acids, such as TDCA, DCA, TCA, CA and increased the ratio of secondary to primary bile acids. FXR and TGR5 deficiency were significantly alleviated. CONCLUSION: PTFC can improve NASH via the the gut microbiota and bile acid metabolism.

6.
Eur J Med Res ; 26(1): 7, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441166

RESUMO

OBJECTIVE: The aim of this study was to detect the expression of interleukin (IL)-1ß and transforming growth factor (TGF)-ß1 in the colonic tissue and serum of irritable bowel syndrome (IBS) rats, as well as the distribution and expression of corticotropin-releasing factor (CRF) in the spinal cord and brain of the visceral hypersensitivity rats, thus to ascertain the mechanism of visceral hypersensitivity signal conduction pathway. METHODS: The expression of IL-1ß and TGF-ß1 in the colonic tissue and serum of IBS rats was screened by the liquid chip technology and verified by RT-PCR technology. Then the quantitative analysis of CRF in the spinal cord and brain was achieved by the immunohistochemical method and computerized image system. RESULT: The rat model with visceral hypersensitivity was successfully established. Among the screened indicators of IL-1ß and TGF-ß1 in colon tissue and serum, only the expression of IL-1ß in the model group was up-regulated (P < 0.05). The immunohistochemical method showed that CRF was expressed in the spinal cord, hypothalamus, and the third ventricle. The positive index number of the model groups was higher than that of the control group (P < 0.01). CONCLUSION: From the research, it can be inferred that IL-1ß may participate in the pathogenesis mechanism of IBS via regulating the colon function. The increasing expression of CRF linked to stress in the spinal cord, hypothalamus and the third ventricle indicated that it might play an important role in the mechanisms of visceral hypersensitivity signal conduction pathway.

7.
Sci Rep ; 11(1): 989, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441676

RESUMO

Macrotermes barneyi, widely distributed in southern China, is the major fungus-growing termite in the subfamily Macrotermitinae. It has no flagellated protists in the guts. Here, we report occurrence of gregarine, a protozoan parasite in the digestive tract of M. barneyi. The general morphology and ultrastructure of the gregarine gamonts and syzygies by light micrograph and scanning electron micrograph are presented. SSU rDNA sequence analysis showed that the termite gregarine has the highest identity (90.10%) to that of Gregarina blattarum from cockroaches. Phylogenetic analysis based on the SSU rDNA sequences from diverse insect eugregarines indicated that the gregarine from M. barneyi is phylogenetically close to G. blattarus, L. erratica and G. tropica from Gregarinidae and Leidyanidae families, and may represent a novel species. This study expands our knowledge about the diversity of terrestrial eugregarines parasitizing in termites.

8.
Learn Mem ; 28(2): 53-71, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33452115

RESUMO

Discrimination of sensory signals is essential for an organism to form and retrieve memories of relevance in a given behavioral context. Sensory representations are modified dynamically by changes in behavioral state, facilitating context-dependent selection of behavior, through signals carried by noradrenergic input in mammals, or octopamine (OA) in insects. To understand the circuit mechanisms of this signaling, we characterized the function of two OA neurons, sVUM1 neurons, that originate in the subesophageal zone (SEZ) and target the input region of the memory center, the mushroom body (MB) calyx, in larval Drosophila We found that sVUM1 neurons target multiple neurons, including olfactory projection neurons (PNs), the inhibitory neuron APL, and a pair of extrinsic output neurons, but relatively few mushroom body intrinsic neurons, Kenyon cells. PN terminals carried the OA receptor Oamb, a Drosophila α1-adrenergic receptor ortholog. Using an odor discrimination learning paradigm, we showed that optogenetic activation of OA neurons compromised discrimination of similar odors but not learning ability. Our results suggest that sVUM1 neurons modify odor representations via multiple extrinsic inputs at the sensory input area to the MB olfactory learning circuit.

9.
Molecules ; 26(2)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445514

RESUMO

The cellular plasma membrane plays a fundamental role in biological processes, including cell growth, signaling and transport. The labelling of the plasma membrane with targeted fluorescent probes offers a convenient and non-invasive way to image the morphological changes and dynamics of a membrane in real-time and, despite many examples of fluorescent plasma membrane probes, a "universal targeting/anchoring moiety" is still required. In this study, a small number of stearic acid-based probes labelled with 6-carboxyfluorescein was designed and fabricated via solid-phase synthesis in which variations in both charge and hydrophobicity were explored. To ease the synthesis process, a gram-scale synthesis of the Fmoc-Lys(6-carboxyfluoresein diacetate)-OH building block was developed, allowing the discovery of optimal probes that carried a positively charged amino group and a stearic acid tail that exhibited intense plasma membrane brightness and robust retention.

10.
Nano Lett ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33448859

RESUMO

Ultrasmall ferrite nanoparticles (UFNPs) have emerged as powerful magnetic resonance imaging (MRI) T1 nanoprobe for noninvasive visualization of biological events. However, the structure-relaxivity relationship and regulatory mechanism of UFNPs remain elusive. Herein, we developed chemically engineered 3.8 nm ZnxFe3-xO4@ZnxMnyFe3-x-yO4 (denoted as ZnxF@ZnxMnyF) nanoparticles with precise dopants control in both crystalline core and disordered shell as a model system to assess the impact of dopants on the relaxometric properties of UFNPs. It is determined that the core-shell dopant architecture allows the optimal tuning of r1 relaxivity for Zn0.4F@Zn0.4Mn0.2F up to 20.22 mM-1 s-1, which is 5.2-fold and 6.5-fold larger than that of the original UFNPs and the clinically used Gd-DTPA. Moreover, the high-performing UFNPs nanoprobe, when conjugated with a targeting moiety AMD3100, enables the in vivo MRI detection of small lung metastasis with greatly enhanced sensitivity. Our results pave the way toward the chemical design of ultrasensitive T1 nanoprobe for advanced molecular imaging.

11.
EMBO Mol Med ; : e13249, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459505

RESUMO

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that occurs in about 1% of individuals over age 60 and is characterized by enlarged cerebral ventricles, gait difficulty, incontinence, and cognitive decline. The cause and pathophysiology of iNPH are largely unknown. We performed whole exome sequencing of DNA obtained from 53 unrelated iNPH patients. Two recurrent heterozygous loss of function deletions in CWH43 were observed in 15% of iNPH patients and were significantly enriched 6.6-fold and 2.7-fold, respectively, when compared to the general population. Cwh43 modifies the lipid anchor of glycosylphosphatidylinositol-anchored proteins. Mice heterozygous for CWH43 deletion appeared grossly normal but displayed hydrocephalus, gait and balance abnormalities, decreased numbers of ependymal cilia, and decreased localization of glycosylphosphatidylinositol-anchored proteins to the apical surfaces of choroid plexus and ependymal cells. Our findings provide novel mechanistic insights into the origins of iNPH and demonstrate that it represents a distinct disease entity.

12.
Orthop Surg ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33480185

RESUMO

Wrist reconstruction after en bloc resection of bone tumors of the distal radius has been a great challenge. Although many techniques have been used for the reconstruction of long bone defects following en bloc resection of the distal radius, the optimal reconstruction method remains controversial. This is the first review to systematically describe various reconstruction techniques. We not only discuss the indications, functional outcomes, and complications of these reconstruction techniques but also review the technical refinement strategies for improving the stability of the wrist joint. En bloc resection should be performed for Campanacci grade III giant cell tumors (GCT) as well as malignant tumors of the distal radius. However, wrist reconstruction after en bloc resection of the distal radius represents a great challenge. Although several surgical techniques, either achieving a stable wrist by arthrodesis or reconstructing a flexible wrist by arthroplasty, have been reported, the optimal reconstruction procedure remains controversial. The purpose of this review was to investigate which reconstruction methods might be the best option by analyzing the indications, techniques, limitations, and problems of different reconstruction methods. With the advancement of imaging, surgical techniques and materials, some reconstruction techniques have been further refined. Each of the techniques discussed in this review has its advantages and disadvantages. Wrist arthrodesis seems to be preferred over wrist arthroplasty in terms of grip strength and long-term complications, while wrist arthroplasty seems to be superior to wrist arthrodesis in terms of wrist motion. All things considered, wrist arthroplasty with a vascularized fibular head autograft might be a good option because of better wrist function, acceptable grip strength, and a relatively lower complication rate. Moreover, wrist arthrodesis is still an option if the fibular head autograft reconstruction fails. Orthopaedic oncologists should familiarize themselves with the characteristics of each technique to select the most appropriate reconstruction method depending on each patient's situation.

13.
J Formos Med Assoc ; 120(1 Pt 1): 48-59, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32334916

RESUMO

BACKGROUND/PURPOSE: Autoimmune diseases are diseases in which the body produces an abnormal immune response to self-antigens and damages its own tissues. Programmed death-1 (PD-1) and its ligands (PD-Ls) have been discovered to be important negative regulators of the immune system, playing crucial roles in autoimmunity. METHODS: We analyzed the existing scientific literature dealing with this issue. In this review, the PD-1/PD-L pathway in the genetic susceptibility to and pathogenesis of rheumatic diseases is discussed. The PD-1/PD-L pathway might be helpful for diagnosing, evaluating the disease activity of and treating rheumatic diseases. RESULTS: PD-1/PD-L gene polymorphisms are associated with a genetic predisposition to rheumatic disorders, which can provide reference information for diagnosis and disease activity. The conclusion of the crucial role of the PD-1/PD-L pathway in the pathogenesis of rheumatic diseases is consistent, but the details remain controversial. In some animal models, manipulating the PD-1/PD-L pathway could decrease disease severity. PD-1/PD-Ls may enable us to develop new therapeutics for patients with rheumatic diseases in the future. CONCLUSION: The PD-1/PD-L pathway plays crucial roles in rheumatic disease. More work is needed to provide a better mechanistic understanding of the PD-1/PD-L pathway and to facilitate the precise therapeutic manipulation of this pathway.

14.
J Cell Physiol ; 236(2): 1295-1308, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32662079

RESUMO

Adipose-derived stromal cells (ADSCs) showed excellent capacity in regeneration and tissue protection. Low tidal volume ventilation (LVT) strategy demonstrates a therapeutic benefit on the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study, therefore, aimed to undertaken determine whether the combined LVT and ADSCs treatment exerts additional protection against lipopolysaccharide (LPS)-induced ALI in rats. The animals were randomized into seven groups: Group I (control), Group II (instillation of LPS at 10 mg/kg intratracheally), Group III (LPS+LVT 6 ml/kg), Group IV (LPS+intravenous autologous 5 × 106 ADSCs which were pretreated with a scrambled small interfering RNA [siRNA] of keratinocyte growth factor [KGF] negative control), Group V (LPS+ADSCs which were pretreated with a scrambled siRNA of KGF, Group VI (LPS+LVT and ADSCs as in the Group IV), and Group VII (LPS+LVT and ADSCs as in the Group V). We found that levels of tumor necrosis factor-α, transforming growth factor-ß1, and interleukin (IL)-1ß and IL-6, the proinflammatory cytokines, were remarkably increased in LPS rats. Moreover, the expressions of ENaC, activity of Na, K-ATPase, and alveolar fluid clearance (AFC) were obviously reduced by LPS-induced ALI. The rats treated by ADSCs showed improved effects in all these changes of ALI and further enhanced by ADSCs combined with LVT treatment. Importantly, the treatment of ADSCs with siRNA-mediated knockdown of KGF partially eliminated the therapeutic effects. In conclusion, combined treatment with ADSCs and LVT not only is superior to either ADSCs or LVT therapy alone in the prevention of ALI. Evidence of the beneficial effect may be partly due to improving AFC by paracrine or systemic production of KGF and anti-inflammatory properties.

15.
Acta Pharm ; 71(1): 99-114, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32697747

RESUMO

Eplerenone is a drug that protects the cardiovascular system. 11α-Hydroxycanrenone is a key intermediate in eplerenone synthesis. We found that although the cytochrome P450 (CYP) enzyme system in Aspergillus ochraceus strain MF018 could catalyse the conversion of canrenone to 11α-hydroxycanrenone, its biocatalytic efficiency is low. To improve the efficiency of 11α-hydroxycanrenone production, the CYP monooxygenase-coding gene of MF018 was predicted and cloned based on whole-genome sequencing results. A recombinant A. ochraceus strain MF010 with the high expression of CYP monooxygenase was then obtained through homologous recombination. The biocatalytic rate of this recombinant strain reached 93 % at 60 h without the addition of organic solvents or surfactants and was 17-18 % higher than that of the MF018 strain. Moreover, the biocatalytic time of the MF010 strain was reduced by more than 30 h compared with that of the MF018 strain. These results show that the recombinant A. ochraceus strain MF010 can overcome the limitation of substrate biocatalytic efficiency and thus holds a high poten tial for application in the industrial production of eplerenone.

16.
J Nanosci Nanotechnol ; 21(1): 450-459, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33213644

RESUMO

During the coalification process, coalbed methane (CBM) is formed and mainly adsorbed in the pores of coal. Pore structure evolution is critical to CBM adsorption/desorption and extraction. This paper puts forward two parameters, namely the variety degree x and variety gene σ, for characterizing pore structure through mercury injection tests. Then, under extraction with different solvents, the dynamic evolution characteristics of nanoscale pores are addressed and quantified by taking four different rank coals (lignite, medium-volatile bituminous coal, low-rank anthracite and mediumrank anthracite) from different coal mines of China as the study object. The results indicate that the content of meso- and macropores after solvent extraction is much larger, but that there is no obvious law with the content of transition pores and micropores in the size range of 50-7.2 nm, according to the basic data sets of specific surface area (SSA) and pore volume (PV) of all coal samples. This phenomenon can be explained by the pore increase and expansion effects in nanoscale pores during solvent extraction. Generally, with the increasing of the solvent extraction degree, the difference in variety degree x with respect to the total PV and total SSA of different coals shows a significant decreasing trend, which expresses a homogeneous development in the change in pore structure. In regard to different solvents, benzene mainly causes pore expansion in meso- and macropores, and CS2 has a great effect on micropores. Whereas acetone plays an important role in mesopores and transition pores with pore expansion, THF has various effects on different size pores. Further study with higher variety gene σ values shows that the total PV mainly depends on the change in the absolute content of meso- and macropores. While the change in the absolute content of transition pores and micropores (less than 50 nm) has a great influence on the total SSA. As the extraction degree increases, the influence of the transition pores and micropores on the total PV is increased, and then, the content of meso- and macropores also plays an important role on the total SSA. However, this effect is highly different for raw coals of different ranks.

17.
Cell ; 184(2): 370-383.e13, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33333023

RESUMO

Proton-coupled monocarboxylate transporters MCT1-4 catalyze the transmembrane movement of metabolically essential monocarboxylates and have been targeted for cancer treatment because of their enhanced expression in various tumors. Here, we report five cryo-EM structures, at resolutions of 3.0-3.3 Å, of human MCT1 bound to lactate or inhibitors in the presence of Basigin-2, a single transmembrane segment (TM)-containing chaperon. MCT1 exhibits similar outward-open conformations when complexed with lactate or the inhibitors BAY-8002 and AZD3965. In the presence of the inhibitor 7ACC2 or with the neutralization of the proton-coupling residue Asp309 by Asn, similar inward-open structures were captured. Complemented by structural-guided biochemical analyses, our studies reveal the substrate binding and transport mechanism of MCTs, elucidate the mode of action of three anti-cancer drug candidates, and identify the determinants for subtype-specific sensitivities to AZD3965 by MCT1 and MCT4. These findings lay out an important framework for structure-guided drug discovery targeting MCTs.

18.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 119065, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33096448

RESUMO

We report the low-temperature studies of liquid CH3CN by Raman spectral measurements at ambient pressure with decreasing the temperature from 20 to -196 °C. Detailed internal modes especially the lattice modes analysis revealed that the structural phase transitions of acetonitrile from liquid to solid phase ß and solid phase ß to solid phase α were occurring at -50 and -60 °C, respectively. Further, the Fermi resonance parameters between the fundamental ν2 and combination (ν3 + ν4) of CH3CN at different temperatures were calculated based on the Bertran's equations. It is found that the Fermi resonance parameters as a function of temperature become discontinued at -50 and -60 °C, which coincides with discontinuities observed in the Raman shifts of CH3CN at -50 and -60 °C. The results suggest that the Fermi resonance parameters could be used as an indicator to assess the structural phase transition for CH3CN under low temperature.

19.
Front Surg ; 7: 587790, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282906

RESUMO

Purpose: To explore the influencing factors of volume hemorrhage in ruptured anterior circulation aneurysms, so as to identify the characteristics of anterior circulation aneurysms with high volume of hemorrhage, and to provide advice for clinical diagnosis and treatment for those aneurysms. Methods: We retrospectively reviewed 437 cases of ruptured anterior intracranial aneurysms in our center between the years 2012 and 2017. According to the inclusion criteria, a total of 100 qualified patients were screened out. We collected demographic characteristics, environmental exposure, and admission status of enrolled patients. In addition, morphological parameters and location of aneurysms were also included. The semiautomatic threshold method was used to measure the volume of hemorrhage. According to the results, the patients were divided into the group with high blood volume and low blood volume. Univariate and multivariate logistic regression analyses were used to discover the related factors affecting the bleeding volume. Results: In univariable analysis, pulse pressure (P = 0.014) showed a significant difference at the P < 0.05 test level. In terms of aneurysm morphology, the irregular shape (P < 0.001), calcification (P = 0.001), and flow angle (P = 0.006) showed significant statistical differences between the two groups at the P < 0.01 level (P < 0.01). Multivariate logistic regression analysis showed that irregular shape (OR = 5.370 P = 0.002 < 0.05), large flow angle (OR = 1.033 P = 0.016 < 0.05), and calcification (OR = 5.460 P = 0.003 < 0.05) were risk factors for volume of hemorrhage in ruptured anterior circulation aneurysms. The influence of hypertension history was at critical state (OR = 2.877 P = 0.051 > 005). Conclusions: According to our analysis results, intracranial anterior circulation aneurysms with irregular shapes, calcifications, and large flow angle are more dangerous. Aneurysms with these characteristics often have a large amount of hemorrhage, requiring timely treatment in clinical practice.

20.
Front Neurol ; 11: 585471, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281722

RESUMO

High-dose steroids, the first-line therapy for acute attacks in neuromyelitis optica spectrum disorder (NMOSD), were ineffective in a proportion of NMOSD attacks. This study aimed to explore possible predictors of high-dose steroid resistance. Demographics and disease characteristics of acute attacks were compared between those who responded to high-dose intravenous methylprednisolone (IVMP) and those resistant to IVMP. In total, 197 attacks in 160 patients were identified in our NMOSD registry. Compared with responders, attacks resistant to high-dose steroids tended to have a higher proportion of previous history of immunosuppressive use (25.5 vs. 15.5%, p = 0.080). Significantly higher levels of proteins in the cerebrospinal fluid (CSF) were found in non-responders than in responders [485.5 (388-656) vs. 387 (291.5-532) mg/L, p = 0.006]. More active lesions were found in the brain stem of non-responders (8 attacks in 55, 14.5%), especially in the pons (7.3%) and medulla (14.5%), as opposed to responders (7 patients in 142, 4.9%). Multivariable logistic regression showed that resistance to high-dose steroid treatment was associated with previous immunosuppressant use [odds ratio (OR), 2.31; 95% confidence interval (CI) 1.002-5.34, p = 0.049], CSF protein level above 450 mg/L (OR 3.42, 95% CI 1.72-6.82, p < 0.001), and active lesions in the brainstem (OR 3.80, 95% CI 1.17-12.32, p = 0.026). In conclusion, NMOSD patients with previous use of immunosuppressants, higher levels of CSF protein, and active lesions in the brainstem are more likely to respond poorly to high-dose IVMP alone during an acute attack.

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