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1.
mSystems ; : e0091521, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609166

RESUMO

The cecum serves as an additional fermentation site for ruminants, but it lacks buffering capacity and has a relatively simple epithelial structure compared to the rumen. The role of high-grain (HG) diets in manipulating the rumen microbiome has been well elucidated, yet the microbial response to such diets in the cecum and the subsequent microbe-host interactions remain largely unexplored. Here, we describe the modification of the cecal microbiome and host epithelial gene expression based on data from 20 sheep grouped to feed an HG diet for 7, 14, and 28 days. Our data indicate that the alteration of cecal microbial fermentation was manifested by a decrease in luminal pH and an increase in acetate and butyrate concentrations following the diet change to HG. We further demonstrate that the alteration of the microbiome was driven by microbes that are likely acetate producers (e.g., Blautia spp. and Akkermansia spp.) and butyrate producers (e.g., Anaerostipes spp. and Roseburia spp.). Moreover, the core microbiota in the cecal microbiome was predominantly maintained after HG diet feeding, while the specific populations of the cecal microbiomes adaptively varied at the species and genomic levels time dependently. Association analysis suggests that the perturbations of the cecal microbiome under the HG diet were closely linked to the variations in the two key enzymes that catalyze the conversion of pyruvate to acetyl-CoA and urease enzymes that hydrolyze urea into ammonia, alongside mucosal inflammatory responses. Overall, our findings here provide novel insights into understanding microbiome-host interactions in the hindgut of ruminants. IMPORTANCE High-grain (HG) diets are known to alter the rumen microbiome. However, the responses of the hindgut microbiota and its epithelial function need further investigation in ruminants. Using 20 sheep as the experimental model, we found that the microbial fermentation pattern of the cecum changed after switching to the HG diet. The taxa of the acetate and butyrate producers increased with the feeding time. Moreover, enzymes engaged in carbon and nitrogen metabolisms of the cecal microbiome are altered. The expression of epithelial genes related to volatile fatty acid (VFA) absorption and metabolism, cytokines, and tight junction proteins, alongside light microscopy visualization of epithelial tissue, suggested that the HG diet may induce cecal mucosal inflammatory responses. Our findings reveal cecal microbial and metabolic perturbations in response to HG diets in sheep and provide a new reference for the research on hindgut microbial homeostasis and host health in ruminants.

2.
Org Lett ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605655

RESUMO

Two pairs of diastereoisomeric isoindoline alkaloids, xylarins A-D (1-4), were isolated from the endolichenic fungus Xylaria sp. Xylarins A and B (1 and 2) possess a previously undescribed 5/6/5-5/6 polycyclic scaffold, featuring a combination of a novel dihydrobenzofurone unit and an isoindoline unit, while xylarins C and D (3 and 4) contain an additional N,N-dimethylaniline at the C-3' position. Their structures were elucidated by comprehensive spectroscopic analyses combined with single-crystal X-ray diffraction and electronic circular dichroism calculations. The plausible biosynthetic pathways and gene clusters for 1-4 were proposed. Compound 1 exhibited significant antithrombotic activity.

3.
J Hum Genet ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34526651

RESUMO

Heterozygous mutations in SPTAN1 are associated with a broad phenotypical spectrum ranging from axonal neuropathy phenotypes to neurodevelopmental phenotypes with or without epilepsy. Recently, biallelic mutations in SPTAN1 were reported as a potential cause of autosomal recessive pure hereditary spastic paraplegia (HSP). However, no further HSP cases with biallelic SPTAN1 mutations have been reported. Herein, we report the clinical and genetic findings of a patient with complicated HSP likely caused by a novel homozygous SPTAN1 mutation. A patient with complicated HSP from a consanguineous family was recruited. The proband underwent detailed neurological examinations. Homozygosity mapping was performed in the proband and her healthy sister. Whole exome sequencing was performed in the proband. Our patient had early onset motor symptoms with upper motor neuron paralysis and intellectual disability, which is compatible with complicated HSP. Genetic analysis identified a rare homozygous missense mutation in SPTAN1 (c.4162A>G, p.I1388V), which was predicted to be deleterious by in silico tools. Her healthy parents and sister all carried the heterozygous mutation. Our results provided further support for the association of biallelic SPTAN1 variants with HSP and suggested that screening for the SPTAN1 gene should be considered not only in patients with pure HSP but also in patients with complicated HSP.

4.
Biochem Biophys Res Commun ; 576: 1-6, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34474244

RESUMO

Wnt signaling is one of the major signaling pathways that regulate cell differentiation, tissue patterning and stem cell homeostasis and its dysfunction causes many human diseases, such as cancer. It is of tremendous interests to understand how Wnt signaling is regulated in a precise manner both temporally and spatially. Naked cuticle (Nkd) acts as a negative-feedback inhibitor for Wingless (Wg, a fly Wnt) signaling in Drosophila embryonic development. However, the role of Nkd remains controversial in later fly development, particularly on the canonical Wg pathway. In the present study, we show that nkd is essential for wing pattern formation, such that both gain and loss of nkd result in the disruption of Wg target expression in larvae stage and abnormal adult wing morphologies. Furthermore, we demonstrate that a thirty amino acid fragment in Nkd, identified previously in Wharton lab, is critical for the canonical Wg signaling, but is dispensable for Wg/planar cell polarity pathway. Putting aside the pleiotropic nature of nkd function, i.e. its role in the Decapentaplegic signaling, we conclude that Nkd universally inhibits the canonical Wg pathway across a life span of Drosophila development.

5.
Eur J Med Chem ; 225: 113821, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34517222

RESUMO

Histone deacetylase 6 (HDAC6) is a potential target for Alzheimer's disease (AD). In this study, a series of novel phenothiazine-, memantine-, and 1,2,3,4-tetrahydro-γ-carboline-based HDAC6 inhibitors with a variety of linker moieties were designed and synthesized. As a hydrochloride salt, the phenothiazine-based hydroxamic acid W5 with a pyridyl-containing linker motif was identified as a high potent and selective HDAC6 inhibitor. It inhibited HDAC6 with an IC50 of 2.54 nM and was more than 290- to 3300-fold selective over other HDAC isoforms. In SH-SY5Y cells, W5 dose-dependently increased the acetylated α-tubulin levels and reduced the hyperphosphorylated tau proteins at Ser396. As an effective metal chelator, W5 inhibited Cu2+-induced Aß1-42 aggregation and disaggregated Cu2+-Aß1-42 oligomers, and showed protective effects on the SH-SY5Y cells against Aß1-42- as well as Cu2+-Aß1-42 induced cell damages, serving as a potential ligand to target AD metal dyshomeostasis. Moreover, W5 promoted the differentiated neuronal neurite outgrowth, increased the mRNA expression of the recognized neurogenesis markers, GAP43, N-myc, and MAP-2. Therefore, W5 might be a good lead for the development of novel HDAC6 inhibitors targeting multi-facets of AD.

6.
Brain Behav ; : e2316, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473429

RESUMO

BACKGROUND: Stroke is a sexually dimorphic disease and a leading cause of death and disability. Estrogen replacement therapy (ERT) confers beneficial neuroprotective effects if administered within a widely accepted time window called the "critical period." However, very few studies have explored the idea of modulating the critical period to enable long-term post-menopausal women to regain more benefits from estrogen therapy. Here, motivated by previous findings that electroacupuncture could both alter estrogen metabolism and induce significant tolerance against stroke, it was explored whether EA could restore estrogen's neuroprotection against cerebral ischemia in long-term ovariectomized (OVX) rats. METHODS: We implemented 1 week(w)-EA pretreatment on OVX-10w or OVX-20w rats, and tested the expression of estrogen receptors, and detected the ERT's neuroprotection against stroke induced by middle cerebral artery occlusion (MCAO). RESULTS: We found that the expression levels of phospho-ERα-S118 and estrogen receptor ß (ERß) in the striatum of OVX-10w rats were significantly decreased and ERT's neuroprotection was abolished in the OVX-10w rats. However, EA-1w pretreatment could significantly recover the expression levels of phospho-ERα-S118 and ERß, and also restored the neuroprotective effects of ERT in OVX-10w rats. However, EA-1w pretreatment could not restore the expression of estrogen receptors and ERT's neuroprotection in OVX-20w rats. CONCLUSION: Taken together, our study indicates that EA may be an easy intervention that can restore the efficacy of estrogen therapy during the "critical period," which has the potential to improve the stroke outcomes of an enormous number of long-term post-menopausal women. However, the time-sensitive influences for how EA and estrogen metabolism interact with each other should be considered.

7.
Mater Horiz ; 8(10): 2823-2833, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34486636

RESUMO

Whilst applying a coating layer to a polymer film is a routine approach to enhance the gas barrier properties of the film, it is counter-intuitive to consider that the gas barrier performance of the film would improve by ageing the coating dispersion for weeks before application. Herein, we report that the oxygen barrier performance of a 12 µm PET film coated with a dispersion of inorganic nanosheets in polyvinyl alcohol can be significantly enhanced by ageing this coating dispersion for up to 8 weeks before application. We found up to a 37-fold decrease in the oxygen transmission rate (OTR) of the PET coated film using aged dispersions of [Mg0.66Al0.33(OH)2](NO3)0.33 layered double hydroxide nanosheets (Mg2Al-LDH NS) in polyvinyl alcohol (PVA) compared to the film coated with an equivalent freshly prepared LDH/PVA dispersion. A limiting OTR value of 0.31 cc m-2 day-1 was achieved using the PET film coated with a 3 week aged LDH NS/PVA dispersion. X-ray diffraction experiments show that the degree of in plane alignment of LDH NS on the PET film surface increased significantly from 70.6 ± 0.6 to 86.7 ± 0.6 (%) (100% represents complete alignment of LDH NS platelets on the film surface) for the 4 week aged dispersion compared to the freshly prepared layer. We postulate that when the Mg2Al-LDH NS are aged in PVA the coiled PVA aggregates start to unwrap and attach onto the Mg2Al-LDH NS through hydrogen bonding and eventually form a hydrogen bonded ordered network that facilitates the alignment of nanosheet dispersions during the coating process. Our results suggest that the ageing of inorganic nanosheet dispersions in PVA or other potential hydrogen bonding adhesive systems could be a general approach to improve the alignment of the nanosheets on the polymer film surface once applied and thus improve their performance characteristics for barrier coating applications.

9.
Dis Markers ; 2021: 9965124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484470

RESUMO

Background: Critical illness in the intensive care unit (ICU) has been a global health priority. Systemic nutritional status has turned out to be related to the prognosis of critically ill patients. The albumin-globulin ratio (AGR) has been reported to be a novel prognostic factor of many diseases. This study is aimed at investigating whether the AGR could predict the mortality risk in critically ill patients. Methods: We enrolled 582 adult patients admitted to the respiratory intensive care unit (RICU). We collected the clinical and laboratory data. X-tile software was used to determine the optimal cut-off values for the AGR. Patients were divided into three groups according to the AGR (low AGR group with AGR < 0.8, medium AGR group with AGR ranging from 0.8 to 1.1, and high AGR group with AGR > 1.1). Kaplan-Meier analysis was used for survival analysis. A Cox proportional hazard model was applied to the univariate and multivariate analyses for the potential predictors associated with survival. Results: Our present study showed that the AGR was related to the 28-day survival of critically ill patients in the RICU. The rate of pneumonia in the low AGR group was significantly higher than that in the other groups. Patients with a lower AGR present an increased risk of 28-day mortality compared to patients with a higher AGR. Cox regression analysis showed that the AGR might be an independent predictor of prognosis to 28-day survival in critically ill patients in the RICU. Medium and high AGR values remained independently associated with better 28-day survival than low AGR values (HR: 0.484 (0.263-0.892) (p = 0.02); HR: 0.332 (0.166-0.665) (p = 0.002)). Conclusion: The AGR might be an independent predictor of prognosis in critically ill patients.

10.
Bioorg Chem ; 116: 105366, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34560561

RESUMO

In recent years, tumor immunotherapy, especially the combination of PD1/PD-L1 inhibitors and chemotherapy, has developed rapidly. However, the systemic side effects induced by chemotherapy remain a crucial problem that needs to be addressed. Antibody drug conjugates (ADCs) are exceptional target-specific prodrugs that greatly improve the therapeutic window of chemotherapy drugs. Therefore, designing PD-L1-targeting ADCs is an interesting research project. In this study, we confirmed for the first time that the commercial anti-PD-L1 antibody Atezolizumab has better endocytosis efficiencies than Avelumab, and was more suitable for ADC design. Then, the most popular cytotoxic payload MMAE was conjugated to Atezolizumab via a classical dipeptide (valine-alanine) linker to generate a bifunctional PD-L1 ADC (ADC 3). An in vitro cytotoxicity test indicated the potent tumor cell inhibitory activity of ADC 3, with EC50 values of 9.75 nM to 11.94 nM. In addition, a co-culture of PBMCs in vitro proved that ADC 3 retained the immune activation effect of the Atezolizumab antibody. Moreover, ADC 3 exhibited a higher tumor inhibition rate and tumor regression rate in humanized immune system mice. To the best of our knowledge, this is the most active PD-L1-ADC reported thus far, which may promote the development of immunotherapy and novel ADCs.

11.
Clin Sci (Lond) ; 135(17): 2085-2097, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34402501

RESUMO

Although extremely important, the molecular mechanisms that govern aortic aneurysm (AA) formation and progression are still poorly understood. This deficit represents a critical roadblock toward the development of effective pharmaceutical therapies for the treatment of AA. While dysregulation of protein phosphatase 2A (PP2A) is thought to play a role in cardiovascular disease, its role in aortic aneurysm is unknown. The objective of the present study is to test the hypothesis that PP2A regulates abdominal aortic aneurysm (AAA) progression in a murine model. In an angiotensin II-induced AAA murine model, the PP2A inhibitor, LB-100, markedly accelerated AAA progression as demonstrated by increased abdominal aortic dilation and mortality. AAA progression was associated with elevated inflammation and extracellular matrix fragmentation, concomitant with increases in both metalloproteinase activity and reactive oxygen species production. Conversely, administration of a novel class of small molecule activators of PP2A (SMAPs) resulted in an antithetical effect. SMAPs effectively reduced AAA incidence along with the corresponding pathologies that were increased with LB-100 treatment. Mechanistically, modulation of PP2A activities in vivo functioned in part via alteration of the ERK1/2 and NFκB signaling pathways, known regulators of AAA progression. These studies, for the first time, demonstrate a role of PP2A in AAA etiology and demonstrate that PP2A activation may represent a novel strategy for the treatment of abdominal aortic aneurysms.

12.
Redox Biol ; 46: 102084, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34364219

RESUMO

Diabetes mellitus (DM) promotes neointimal hyperplasia, characterized by dysregulated proliferation and accumulation of vascular smooth muscle cells (VSMCs), leading to occlusive disorders, such as atherosclerosis and stenosis. Poly (ADP-ribose) polymerase 1 (PARP1), reported as a crucial mediator in tumor proliferation and transformation, has a pivotal role in DM. Nonetheless, the function and potential mechanism of PARP1 in diabetic neointimal hyperplasia remain unclear. In this study, we constructed PARP1 conventional knockout (PARP1-/-) mice, and ligation of the left common carotid artery was performed to induce neointimal hyperplasia in Type I diabetes mellitus (T1DM) mouse models. PARP1 expression in the aorta arteries of T1DM mice increased significantly and genetic deletion of PARP1 showed an inhibitory effect on the neointimal hyperplasia. Furthermore, our results revealed that PARP1 enhanced diabetic neointimal hyperplasia via downregulating tissue factor pathway inhibitor (TFPI2), a suppressor of vascular smooth muscle cell proliferation and migration, in which PARP1 acts as a negative transcription factor augmenting TFPI2 promoter DNA methylation. In conclusion, these results suggested that PARP1 accelerates the process of hyperglycemia-induced neointimal hyperplasia via promoting VSMCs proliferation and migration in a TFPI2 dependent manner.

13.
J Viral Hepat ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464991

RESUMO

Hepatitis B viral (HBV) load and hepatic enzymes play a critical role in hepatocellular carcinoma (HCC) development. However, the clinical significance of these in HBV-related HCC patients after hepatectomy remains unclear. In this study, we analysed 1,940 HBV-related HCC patients who underwent hepatectomy from four hospitals in west China. Risk classification was constructed based on baseline HBV-DNA load and AST/ALT ratio. Based on the HBV-DNA load and AST/ALT ratio classification, four types with distinguishable prognoses were established. Type 1 patients had the best prognosis with 5-year overall survival (OS) of 69.8%, followed by type 2 and type 3 patients, whereas type 4 patients had the worst prognosis with 5-year OS of 42.7%. Similarly, the four types had statistically different recurrence-free survival. This classification was significantly associated with HCC recurrence (hazard ratio [HR]:1.492, p < .001) and long-term survival (HR: 1.574, p = .001). Pathologically, type 4 correlated with more advanced tumours considering tumour size and microvascular invasion than those in type 1, 2, or 3. Moreover, type 4 patients had more severe hepatic inflammation in underlying liver. Conversely, type 1 patients had an active tumour immune microenvironment as indicated by more CD8+ T cell infiltration and less PD-L1 expression. In conclusion, the classfication based on baseline HBV-DNA load and AST/ALT ratio could effectively stratify HBV-related HCC patients with distinguishable prognoses after hepatectomy.

14.
Sci Total Environ ; 799: 149334, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34364269

RESUMO

Denitrifying anaerobic methane oxidation (DAMO) is an important microbial metabolic process that simultaneously converts of methane and nitrite. In this study, electrochemical systems were investigated for DAMO with nitrite as an electron acceptor. The results showed that the auxiliary voltage enhanced anaerobic methane oxidation and nitrite reduction. The greatest methane conversion (26.61 mg L-1 d-1) was obtained at an auxiliary voltage of 1.6 V (EMN-1.6). Isotope tracing indicated that carbon dioxide was the oxidation product of methane, and methanol was the intermediate. The power density reached 0.60 (for EMN-0.5, the bioreactor with a voltage of 0.5 V) and 3.77 mW m-2 (for EMN-1.6). DAMO microbes, Methylocystis sp., and Methylomonas sp. were identified as methanotrophs. Rhodococcus sp., Hyphomicrobium sp., and Thiobacillus sp. were the dominant denitrifying bacteria. The conversion pathway was speculated to be as follows: methane was oxidized to carbon dioxide and nitrite was reduced to nitrogen. The two processes were independently completed by DAMO bacteria and oxygen was simultaneously generated. For the electron transfer pathway, methanotrophs utilized the oxygen released by DAMO bacteria to convert methane into organic matter (e.g. methanol). These organic compounds were utilized by Pseudoxanthomonas sp. and Pseudomonas sp., and the generated electrons were then released to the outside of the cells and transferred to the anode. Denitrifying bacteria received electrons at the cathode, transferred them to the interior of the cell, and then converted nitrite into nitrogen. This research explored an effective consortium and a method for methane and nitrogen removal.

15.
J Mol Cell Cardiol ; 161: 39-52, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34343541

RESUMO

Calcification is common in atherosclerotic plaque and can induce vulnerability, which further leads to myocardial infarction, plaque rupture and stroke. The mechanisms of atherosclerotic calcification are poorly characterized. Interleukin enhancer binding factor 3 (ILF3) has been identified as a novel factor affecting dyslipidemia and stroke subtypes. However, the precise role of ILF3 in atherosclerotic calcification remains unclear. In this study, we used smooth muscle-conditional ILF3 knockout (ILF3SM-KO) and transgenic mice (ILF3SM-Tg) and macrophage-conditional ILF3 knockout (ILF3M-KO) and transgenic (ILF3M-Tg) mice respectively. Here we showed that ILF3 expression is increased in calcified human aortic vascular smooth muscle cells (HAVSMCs) and calcified atherosclerotic plaque in humans and mice. We then found that hyperlipidemia increases ILF3 expression and exacerbates calcification of VSMCs and macrophages by regulating bone morphogenetic protein 2 (BMP2) and signal transducer and activator of transcription 1 (STAT1) transcription. We further explored the molecular mechanisms of ILF3 in atherosclerotic calcification and revealed that ILF3 acts on the promoter regions of BMP2 and STAT1 and mediates BMP2 upregulation and STAT1 downregulation, which promotes atherosclerotic calcification. Our results demonstrate the effect of ILF3 in atherosclerotic calcification. Inhibition of ILF3 may be a useful therapy for preventing and even reversing atherosclerotic calcification.

16.
Transl Oncol ; 14(11): 101187, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34365221

RESUMO

BACKGROUND: To evaluate the value of locoregional radiotherapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (dmNPC) and identify predictive factors for additional LRRT after palliative chemotherapy (PCT). METHODS: Overall survival (OS) was the primary endpoint. Patients who underwent PCT and LRRT were categorized as the PCT+LRRT group; patients who only received palliative chemotherapy were categorized as the PCT group. Oligometastatic diseases (OMD) was defined as ≤5 metastatic lesions and ≤2 metastatic organs. RESULTS: A total of 168 patients were included for this study. The median OS of patients in the PCT+LRRT group was significantly higher than those in the PCT group (57 months vs. 22 months, P<0.001). Multivariate analyses (MVA) showed that LRRT (HR=0.533, 95% CI: 0.319-0.889, P = 0.016) and OMD (HR=0.548, 95% CI: 0.331-0.907, P = 0.019) were independent prognostic factors for dmNPC. Furthermore, Kaplan-Meier analyses showed that the 3-year OS of patients who received LRRT was significantly better than those who did not receive LRRT in the OMD subgroup (66.3% vs. 25.2%, P<0.001). While, the 3-year OS of patients who received LRRT and without LRRT was no different in the polymetastatic disease (PMD) subgroup (38.9% vs.11.5%, P = 0.115). MVA showed that LRRT was a favorable prognosticator in the OMD subgroup (HR=0.308, 95% CI: 0.159-0.598; P<0.001), and not a favorable prognosticator in the PMD subgroup (HR=0.510, 95% CI: 0.256-1.014, P = 0.055). CONCLUSIONS: LRRT has the potential to prolong OS in NPC patients with de novo OMD. These results suggest that OMD is a potential indicator for filtering beneficiaries from LRRT.

17.
Intern Med ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34433720

RESUMO

The patient had suffered from both proximal and distal limb weakness since her early childhood, without the involvement of ocular or respiratory muscles. Repetitive nerve stimulation (RNS) at 3 Hz showed significant decrement in the area and amplitude of the compound muscle action potential (CMAP) on the right abductor digiti minimi (26%) and trapezius (17%). Whole-exon sequencing revealed two novel heterozygous mutations (p.Q1406Rfs*29 and p.R1521H) in the LG1 domain of agrin, which were deemed likely pathogenic for congenital myasthenic syndromes (CMS) according to a bioinformatics analysis. The patient showed remarkable improvement after treatment with salbutamol. This case expanded the mutation spectrum of AGRN.

18.
Medicine (Baltimore) ; 100(32): e26904, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397921

RESUMO

RATIONALE: Persistent primitive hypoglossal artery (PPHA) is a rare and permanent carotid-vertebrobasilar anastomoses. Patients with PPHA usually have higher changes of developing intracranial aneurysms due the high intracranial hemodynamics. Although cases of PPHA alone and PPHA with aneurysms have been reported in literature, cases of fenestrated PPHA harboring a ruptured aneurysm have seldomly be reported in literature. We present a rare occurrence of a fenestrated PPHA harboring a reputed aneurysm. PATIENTS CONCERNS: A 43-year-old woman was presented with a sudden-onset severe headache and nausea. DIAGNOSIS: Computerized tomography scan showed third, fourth, and bilateral ventricular hemorrhages. Computed tomographic angiogram showed a PPHA with fenestration malformation and a cystic protrusion consistent with an aneurysm. INTERVENTION: The patient underwent a successful stent-assisted coil embolization via the trans-arterial route under general anesthesia. OUTCOMES: Two years follow-up revealed no recurrence of her symptomatology and she is currently well and go about her normal daily life. CONCLUSION: Fenestrated PPHAs harboring aneurysms may be more prone to rupture because of the fenestration and connective tissue weakness of the artery as well as changes in hemodynamics of the already malformed and weak artery.


Assuntos
Aneurisma Roto/diagnóstico , Artéria Basilar , Angiografia Cerebral/métodos , Aneurisma Intracraniano/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Anastomose Cirúrgica/métodos , Aneurisma Roto/cirurgia , Feminino , Humanos , Aneurisma Intracraniano/cirurgia
19.
Artigo em Chinês | MEDLINE | ID: mdl-34304509

RESUMO

Objective:To explore the differences in cognitive function between patients with severe OSA and non-moderate OSA. Methods:The MoCA scale was used to evaluate the overall cognitive function and sub-items in 196 subjects who received polysomnography; and the SDMT and TMT-A scales were used to evaluate the performance in test of attention and information processing speed in 161 patients. The clinical information, physical examination data and related polysomnography data were collected. According to AHI, subjects were divided into two groups: severe OSA and non-to-moderate OSA. Before and after correction of confounding factors, the differences in cognitive scale evaluation indicators were compared between the two groups. We used linear regression analysis to clarify the independent influencing factors of cognitive functions, and to determine whether severe OSA is independently related to cognitive abilities. Results:After correcting for multiple factors, the delayed recall score and total score of the MoCA scale and the correct number of SDMT in the severe OSA group were significantly lower than those in the non-to-moderate OSA group(P<0.05). Linear regression analysis showed that severe OSA was independently negatively correlated with the delayed recall score, total score and SDMT correct number in the MoCA scale(P<0.05). Conclusion:Compared with non-to-moderate OSA, subjects with severe OSA have significant decline in overall cognition, delayed recall, attention and processing speed. Severe OSA may be an independent influencing factor of overall cognition, delayed recall, attention and processing speed.


Assuntos
Apneia Obstrutiva do Sono , Atenção , Cognição , Humanos , Polissonografia , Apneia Obstrutiva do Sono/complicações
20.
J Hum Evol ; 157: 103033, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34246050

RESUMO

In contrast to the prevailing view that the Chinese Paleolithic has been dominated by the Mode 1 technology-with a slow and conservative development from the Early to the Late Pleistocene-recent discoveries indicate that the lithic technology might have developed into an 'advanced' phase in some parts of China, at least since the early Late Pleistocene. The Xinmiaozhuang Locality 1 (XMZ1), located on the southern edge of the Nihewan Basin in northern China, is one of the examples belonging to such an 'advanced' phase. Although the stone artifacts at this site still belong to the long-existing 'small-tool' industry (core-and-flake) in this basin, some 'advanced' traits, including discoidal cores, elongated flakes, and 'Mousterian-like' triangular points and scrapers, are present. We provide a dating of the XMZ1 using the multiple elevated temperatures (MET) post infrared (pIR) infrared stimulated luminescence (IRSL) procedure (MET-pIRIR) on both multigrained single aliquots and 'individual' grains of potassium-rich feldspars (K-feldspars). The consistency between the single-aliquot and single-grain K-feldspar equivalent dose results mutually confirmed the reliability of the obtained ages. Our chronology indicates that the cultural layer falls within the period of ca. 63-75 ka, corresponding to the early stage of the Marine Isotope Stage (MIS) 4. Based on the correlation of the cultural age to the environmental proxies of loess and stalagmites from China, we suggest that the site might have witnessed dramatic fluctuations of paleoclimate during the site formation. Additionally, based on the discoidal cores distribution, a potential corridor along the Xuefeng-Wu-Tainhang-Great Khingan Mountains for ancient humans migrating between South and North China is suggested. However, more archaeological and chronological studies are required to figure out the origin and the dispersal patterns of the discoidal core associated with lithic assemblage and the tool-makers in East Asia.

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