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OBJECTIVES: Delirium is a significant health concern in acute stroke patients. We aim to systematically summarize existing evidence to conduct a meta-analysis to quantify the occurrence and risk factors for delirium after acute stroke. METHOD: PubMed, EMBASE and MEDLINE were searched from inception to Feb. 2023 for prospective observational studies that reported the incidence or prevalence of post-stroke delirium and/or evaluated potential risk factors. The search strategy was created using controlled vocabulary terms and text words for stroke and delirium. We performed a meta-analysis of the estimates for occurrence and risk factors using random-effects models. Meta-regression and subgroup meta-analyses were conducted to explore the sources of heterogeneity. Study quality and quality of evidence were assessed using the customized Newcastle-Ottawa Scale and GRADE, respectively. RESULTS: Forty-nine studies that enrolled 12383 patients were included. The pooled occurrence rate of post-stroke delirium was 24.4â¯% (95â¯%CI, 20.4â¯%-28.9â¯%, I2=96.2â¯%). The pooled occurrence of hyperactive, hypoactive, and mixed delirium was 8.5â¯%, 5.7â¯% and 5.0â¯%, respectively. Study location, delirium assessment method and stroke type independently affected the heterogeneity of the pooled estimate of delirium. Statistically significant risk factors were older age, low education level, cigarette smoking, alcohol drinking, atrial fibrillation, lower ADL level, higher pre-stroke mRS score, premorbid cognitive impairment or dementia, aphasia, total anterior circulation impairment, higher National Institute of Health Stroke Scale score and infection. CONCLUSIONS: Delirium affected 1 in 4 acute stroke patients, although reported rates may depend on assessment method and stroke type. Timely prevention, recognition and intervention require prioritizing patients with dominant risk factors.
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OBJECTIVE: To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy. METHODS: After retrospectively screening the data of 742 patients between January 2007 and July 2020, 50 patients aged 13 to 39 years with Enneking stage II disease were included in the study. Serum lipid levels, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-α [Lp(a)], and apolipoprotein A1, B, and E (ApoA1, ApoB, and ApoE), and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy. RESULTS: The mean levels of TC, TG, and ApoB were significantly increased following neoadjuvant chemotherapy (16%, 38%, and 20%, respectively, vs. pretreatment values; P<0.01). The mean levels of LDL-C and ApoE were also 19% and 16% higher, respectively (P<0.05). No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy. An increase in Lp(a) was strongly correlated with the Ki-67 index (R=0.31, P=0.023). Moreover, a trend toward longer disease-free survival (DFS) was observed in patients with decreased TG and increased LDL-C following chemotherapy, although this difference was not statistically significant (P=0.23 and P=0.24, respectively). CONCLUSION: Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma. There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy. The scale of increase in serum Lp(a) might have a potential prognostic role in osteosarcoma. Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.
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Three samples whose growth temperatures were 450°C, 500°C, and 560°C for S E S A M 1, S E S A M 2, and S E S A M 3, respectively, were tested by femto-second time-resolved transient absorption spectroscopy. The results indicate that the carrier dynamics of excited state absorption were dominant, and the lifetimes of carriers trapped by defect levels were about tens of pico-seconds. To further study the influence of carrier dynamics and recovery time of samples by ion-implantation, B + ions of 80 and 130 KeV were implanted into the samples with dose of 1014/c m 2. The modified samples showed a dominance of ultra-fast carrier dynamics of ground-state bleaching and direct recombination, which lasted for hundreds of femto-seconds, over excited state absorption. Additionally, carrier fast trapping was observed to be competitive with the excited state absorption process. After ion-implantation, the carrier dynamics of carrier trapping were enhanced, which contributed to forming an ultra-short laser, while the carrier dynamics of absorption of the excited state were suppressed. The conclusion that defect levels were partially eliminated by B + ion-implantation can be drawn.
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RATIONALE: Percutaneous transhepatic biliary drainage (PTBD) plays a significant role especially in the diagnosis and decompression of bile duct obstruction. However, it is associated with complications such as hemobilia, occlusion of drainage, bile leakage, and even bronchobiliary fistula (BBF). PATIENT CONCERNS AND DIAGNOSES: We herein describe a patient with a complication of BBF caused by long-term indwelling PTBD catheters. She underwent multiple operations including bilioenteric anastomosis, hepatic left lateral lobectomy, and long-term PTBD treatment. Her symptoms were mainly cough, fever, and yellow sputum and her diagnosis was confirmed by sputum culture (bilirubin detection was positive). INTERVENTIONS AND OUTCOMES: The patient recovered uneventfully by minimally invasive treatment, was discharged after 1 week of hospitalization, and the drainage tube was removed 2 weeks later. During 2 years of follow-up, no recurrence of BBF was observed. LESSONS: Patients with long-term indwelling PTBD catheters for biliary tract obstruction may lead to BBF. The treatment plan of BBF is tailored to the patient's individualized characteristics. And minimally invasive treatments might be an effective alternate way for the treatment of BBF. The accurate diagnosis, precision treatment, and multidisciplinary team play important roles in the treatment of BBF.
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Fístula Biliar , Colestase , Humanos , Feminino , Fístula Biliar/diagnóstico , Fístula Biliar/etiologia , Fístula Biliar/cirurgia , Colestase/complicações , Drenagem/efeitos adversos , Catéteres/efeitos adversos , Anastomose Cirúrgica/efeitos adversosRESUMO
Aims: This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). Methods: The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions. Results: A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (pï¼0.05), which were selected to construct TF-gene interaction and TF-miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD. Conclusion: The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets.
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BACKGROUND: While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine. METHODS: We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine. We also combined data from GWAS of migraine with a novel joint-tissue imputation (JTI) prediction model of 17 migraine-related human tissues to conduct transcriptome-wide association studies (TWAS) together with the fine mapping method FOCUS to identify disease-associated genes. RESULTS: We identified 13 genes in the human brain and plasma proteome that modulate migraine risk by regulating protein abundance. In addition, 62 associated genes not reported in previous migraine TWAS studies were identified by our analysis of migraine using TWAS and fine mapping. Five genes including ICA1L, TREX1, STAT6, UFL1, and B3GNT8 showed significant associations with migraine at both the proteome and transcriptome, these genes are mainly expressed in ependymal cells, neurons, and glial cells, and are potential target genes for prevention of neuronal signaling and inflammatory responses in the pathogenesis of migraine. CONCLUSIONS: Our proteomic and transcriptome findings have identified disease-associated genes that may give new insights into the pathogenesis and potential therapeutic targets for migraine.
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Transtornos de Enxaqueca , Proteoma , Humanos , Proteoma/genética , Estudo de Associação Genômica Ampla , Proteômica , Transcriptoma , Transtornos de Enxaqueca/genéticaRESUMO
Episodic syndromes that may be associated with migraine@#Episodic syndromes that may be associated with migraine are commonly seen in children and are likely to evolve into migraine in the subsequent course of the disease, including several subtypes such as benign paroxysmal torticollis, benign paroxysmal vertigo, and recurrent gastrointestinal disturbance. Understanding the above syndromes has an important clinical significance in the diagnosis of migraine in children.
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Transtornos de EnxaquecaRESUMO
Meningioangiomatosis (MA) is a disease that is extremely rarely reported. Sporadic MA is occasionally combined with meningioma or other lesions (identified as non-pure MA). This retrospective study investigated the difference between pure MA and non-pure MA by exploring clinical manifestations, histopathology characteristics, and outcomes of MA after surgery. We reviewed the medical records of 36 histopathologically confirmed MA patients (18 pure MA and 18 non-pure MA) who received surgery at our institution between 2012 and 2021. We compared differences in demographic, clinical, imaging, pathological features, and surgical outcomes between pure MA and non-pure MA through descriptive statistics. Compared to non-pure MA, pure MA presented with a more prominent male predilection (5:1 vs. 1.57:1, P = 0.264), a higher seizure incidence (83.3% vs 50.0%, P = 0.038), a more seizure type of GTCS (14/15 vs 5/9, P = 0.047), a less prominent enhancement on MRI (27.8% vs 88.9%, P < 0.001) and a preference of temporal and frontal lobe (100% vs 44.4%, P < 0.001). The differences in clinical characteristics between pure MA and non-pure MA demonstrate their disparate biological natures. Pure MA seems to be a non-neoplastic lesion, while non-pure MA is commonly combined with meningioma, which is a neoplastic lesion. A correct differential diagnosis can be achieved via a triad of the type of seizure, the location of lesion and the radiological presentation. MA is curable and the prognosis is excellent as most patients are free of seizure and recurrence after surgical treatment.
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Malformações Vasculares do Sistema Nervoso Central , Neoplasias Meníngeas , Meningioma , China , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico , Meningioma/patologia , Meningioma/cirurgia , Prognóstico , Estudos Retrospectivos , Convulsões/etiologiaRESUMO
Objective: The brain compensation mechanism in postoperative delirium (POD) has not been reported. We uncovered the mechanism by exploring the association between POD and glioma grades, and the relationship between preoperative brain structural and functional compensation with POD in patients with frontal glioma. Methods: A total of 335 adult patients with glioma were included. The multivariable analysis examined the association between tumor grade and POD. Then, 20 patients with left frontal lobe glioma who had presurgical structural and functional MRI data and Montreal Cognitive Assessment (MoCA) in this cohort were analyzed. We measured the gray matter volume (GMV) and functional connectivity (FC) in patients with (n = 8) and without (n = 12) POD and healthy controls (HCs, n = 29) to detect the correlation between the structural and functional alteration and POD. Results: The incidence of POD was 37.3%. Multivariable regression revealed that high-grade glioma had approximately six times the odds of POD. Neuroimaging data showed that compared with HC, the patients with left frontal lobe glioma showed significantly increased GMV of the right dorsal lateral prefrontal cortex (DLPFC) in the non-POD group and decreased GMV of right DLPFC in the POD group, and the POD group exhibited significantly decreased FC of right DLPFC, and the non-POD group showed the increasing tendency. Partial correlation analysis showed that GMV in contralesional DLPFC were positively correlated with preoperative neurocognition, and the GMV and FC in contralesional DLPFC were negatively correlated with POD. Conclusions: Our findings suggested that insufficient compensation for injured brain regions involving cognition might be more vulnerable to suffering from POD.
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ConspectusBuilding rechargeable batteries for subzero temperature application is highly demanding for various specific applications including electric vehicles, grid energy storage, defense/space/subsea explorations, and so forth. Commercialized nonaqueous lithium ion batteries generally adapt to a temperature above -20 °C, which cannot well meet the requirements under colder conditions. Certain improvements have been achieved with nascent materials and electrolyte systems but have mainly been restrained to discharge and within a small rate at temperatures above -40 °C. Moreover, the recharging process of batteries based on the graphite anode still faces huge challenges from the simultaneous Li+ intercalation and potential Li stripping at subzero temperatures. Revealing the temperature-dependent evolution of physicochemical and electrochemical properties will greatly benefit our understanding of the limiting factors at low temperature, which is of significant importance.Herein, we dissect the ion movements in the liquid electrolyte and solid electrode as well as their interphase to analyze the temperature effect on Li+-diffusion behavior during charging/discharging processes. An electrolyte is the vital factor, and its ionic conductivity guarantees the smooth operation of the battery. However, it is the sluggish diffusion in the solid, especially the charge transfer at the solid electrolyte/electrode interfaces (SEI), that greatly limits the kinetics at low temperature. Many strategies have been put forward to tame electrolytes for low-temperature application. From a macroscopic point of view, multiple solvents are mixed to adjust the liquid temperature range and viscosity. With respect to the microscopic nature, research is focusing on the solvation structure by formulating the ratio of Li+ ions to solvent molecules. The binding energy of the Li+-solvent complex is crucial for the desolvation process at low temperature, which is manipulated with fluorinated solvents or other weakly solvating electrolytes. On the basis of an optimized electrolyte, electrodes and their reaction mechanism need to be coupled carefully because different materials show totally different responses to temperature change. To avoid the sluggish desolvation process or slow diffusion in the bulk intercalation compounds, several kinds of materials are summarized for low temperature use. The intercalation pseudocapacitive behavior can compensate for the kinetics to some extent, and a metal anode is a good candidate for replacing a graphite anode to build high-energy-density batteries at subzero temperature. It is also a wise choice to develop nascent battery chemistry based on the co-intercalation of solvent molecules into electrodes. Furthermore, the interfacial resistance contributes a lot at low temperature, which need be modified to accelerate the Li+ diffusion across the film. This will be linked to the electrolyte, exactly speaking, the solvation structure, to regulate the organic and inorganic components as well as the structure. Although it is difficult to investigate SEI on a graphite anode owing to its poor performance at low temperature, great efforts on Li metal anodes have offered some valuable information as reference. It is worth mentioning that the improvement in low-temperature performance calls for not only a change in the single composition but also the synergetic effect of each part in the whole battery. The elementary studies covered in this account could be taken as insight into some key strategies that help advance the low-temperature battery chemistry.
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BACKGROUND: To investigate the predictive value of blood ammonia (BLA) quantification in the prognosis of acute liver failure (ALF). METHODS: Seventy-one patients with ALF were enrolled and BLA concentration was measured in all patients. After following up for 28 days, patients were divided into two groups: the surviving group (n = 21) and the deceased group (n = 50). An independent-samples t-test was used to compare BLA concentrations between the two groups, and receiver operating characteristic curves were used to ¬evaluate the predictive value of BLA in the prognosis of ALF. A fourfold table analysis was performed with the determined BLA cutoff value. RESULTS: The average concentration of BLA in the deceased group was significantly higher compared with the surviving group (144.50 µmol/L vs. 106 µmol/L, respectively; P = .035). The cutoff BLA concentration for a good ALF prognosis was 122.5 µmol/L. The area under the curve was 0.659. Both the sensitivity and specificity were >0.6. The 95% CIs for sensitivity and specificity were 0.452-0.733 and 0.477-0.878, respectively. The fourfold table analysis revealed a positive predictive value of 83.3%, a negative predictive value of 42.9%, a misdiagnosis rate of 28.6%, and an accuracy of 63.4%. CONCLUSION: With a cutoff BLA concentration of 122.5 µmol/L, the prognosis of ALF could be predicted with high sensitivity and specificity, a positive predictive value, a low misdiagnosis rate, and good accuracy.
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Amônia , Falência Hepática Aguda , Amônia/sangue , Humanos , Falência Hepática Aguda/diagnóstico , Prognóstico , Curva ROC , Estudos RetrospectivosAssuntos
Granulomatose com Poliangiite , Neoplasias , Doenças Uretrais , Fístula Urinária , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Humanos , Doenças Uretrais/diagnóstico , Doenças Uretrais/etiologia , Fístula Urinária/diagnóstico por imagem , Fístula Urinária/etiologiaRESUMO
In this study, a higher metal ions-resistant bacterium, Stenotrophomonas rhizophila JC1 was isolated from contaminated soil in Jinchang city, Gansu Province, China. The Pb2+ (120 mg/L) and Cu2+ (80 mg/L) removal rate of the strain reached at 76.9% and 83.4%, respectively. The genome comprises 4268161 bp in a circular chromosome with 67.52% G + C content and encodes 3719 proteins. The genome function analysis showed czc operon, mer operon, cop operon, arsenic detoxification system in strain JC1 were contributed to the removal of heavy metals. Three efflux systems (i.e., RND, CDF, and P-ATPase) on strain JC1 genome could trigger the removal of divalent cations from cells. cAMP pathway and ABC transporter pathway might be involved in the transport and metabolism of heavy metals. The homology analysis exhibited multi-gene families such as ABC transporters, heavy metal-associated domain, copper resistance protein, carbohydrate-binding domain were distributed across 410 orthologous groups. In addition, heavy metal-responsive transcription regulator, thioredoxin, heavy metal transport/detoxification protein, divalent-cation resistance protein CutA, arsenate reductase also played important roles in the heavy metals adsorption and detoxification process. The complete genome data provides insight into the exploration of the interaction mechanism between microorganisms and heavy metals.
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Proteínas de Membrana Transportadoras/genética , Metais Pesados/metabolismo , Metais Pesados/toxicidade , Stenotrophomonas/genética , Stenotrophomonas/metabolismo , Composição de Bases/genética , China , Inativação Metabólica/genética , Inativação Metabólica/fisiologia , Solo/química , Stenotrophomonas/efeitos dos fármacos , Sequenciamento Completo do GenomaRESUMO
Moyamoya-like vasculopathy, the "puff of smoke"-like small vessels in the brain, is initially identified in patients with Moyamoya disease (MMD), a rare cerebrovascular disease, and later found in patients with various types of neurological conditions, including Down syndrome, Stroke, and vascular dementia. It is thus of interest to understand how this vasculopathy is developed. Here, we provided evidence for cortical astrocytic neogenin (NEO1) deficiency to be a risk factor for its development. NEO1, a member of deleted in colorectal cancer (DCC) family netrin receptors, was reduced in brain samples of patients with MMD. Astrocytic Neo1-loss resulted in an increase of small blood vessels (BVs) selectively in the cortex. These BVs were dysfunctional, with leaky blood-brain barrier (BBB), thin arteries, and accelerated hyperplasia in veins and capillaries, resembled to the features of moyamoya-like vasculopathy. Additionally, we found that both MMD patient and Neo1 mutant mice exhibited altered gene expression in their cortex in proteins critical for not only angiogenesis [e.g., an increase in vascular endothelial growth factor (VEGFa)], but also axon guidance (e.g., netrin family proteins) and inflammation. In aggregates, these results suggest a critical role of astrocytic NEO1-loss in the development of Moyamoya-like vasculopathy, providing a mouse model for investigating mechanisms of Moyamoya-like vasculopathy.
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Astrócitos/metabolismo , Barreira Hematoencefálica/metabolismo , Proteínas de Membrana/deficiência , Doença de Moyamoya/metabolismo , Córtex Pré-Frontal/metabolismo , Adulto , Animais , Astrócitos/patologia , Barreira Hematoencefálica/patologia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Doença de Moyamoya/genética , Doença de Moyamoya/patologia , Córtex Pré-Frontal/patologiaRESUMO
Rechargeable Na-air batteries (NABs) based on abundant Na resources are generating great interest due to their high energy density and low cost. However, Na anode corrosion in ambient air and the growth of abnormal dendrites lead to insufficient cycle performance and safety hazards. Effectively protecting the Na anode from corrosion and inducing the uniform Na plating and stripping are therefore of vital importance for practical application. We herein report a NAB with in situ formed gel electrolyte and Na anode with trace residual Li. The gel electrolyte is obtained within cells through cross-linking Li ethylenediamine at the anode surface with tetraethylene glycol dimethyl ether (G4) from the liquid electrolyte. The gel can effectively prevent H2O and O2 crossover, thus delaying Na anode corrosion and electrolyte decomposition. Na dendrite growth was suppressed by the electrostatic shield effect of Li+ from the modified Li layer. Benefiting from these improvements, the NAB achieves a robust cycle performance over 2000 h in opened ambient air, which is superior to previous results. Gelation of the electrolyte prevents liquid leakage during battery bending, facilitating greater cell flexibility, which could lead to the development of NABs suitable for wearable electronic devices in ambient air.
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Spinal cord injury can lead to severe motor, sensory and autonomic nervous dysfunctions. However, there is currently no effective treatment for spinal cord injury. Neural stem cells and progenitor cells, bone marrow mesenchymal stem cells, olfactory ensheathing cells, umbilical cord blood stem cells, adipose stem cells, hematopoietic stem cells, oligodendrocyte precursor cells, macrophages and Schwann cells have been studied as potential treatments for spinal cord injury. These treatments were mainly performed in animals. However, subtle changes in sensory function, nerve root movement and pain cannot be fully investigated with animal studies. Although these cell types have shown excellent safety and effectiveness in various animal models, sufficient evidence of efficacy for clinical translation is still lacking. Cell transplantation should be combined with tissue engineering scaffolds, local drug delivery systems, postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal life. This review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury, with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.
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BACKGROUND: Chordoid gliomas (CGs) are rare neuroepithelial tumors, which commonly arise from the anterior part of the third ventricle. Most studies on CGs included only one or two cases. To better understand the disease, we report 14 patients with pathologically confirmed CGs. METHOD: The clinical characteristics, including radiological and histological examination, operative records, and prognoses were analyzed and reviewed. RESULT: The case series included six male and eight female patients with an average age of 44.4 years. The most common preoperative symptom was headache (64.3%) and visual deterioration (57.1%). Radiological results showed that the third ventricle (12/14) was the most common site of the brain involved, and the lesions presented with solid (n = 9, 64.3%) or cystic-solid (n = 5, 35.7%) appearance. All patients were misdiagnosed as non-CG tumors. The operation approach was mainly determined by tumor location, thus trans-callosal approach (9/14) and trans-laminar terminalis approach were commonly used. Gross total resection (GTR) was achieved in all cases and none of them received any adjuvant therapy postoperatively. The most frequent postoperative complications were diabetes insipidus, electrolyte disturbance, hypopituitarism, cognitive dysfunction, and obstructive hydrocephalus. During an average follow-up period of 40.1 months, 2 cases (14.3%) were died of refractory hypopituitarism and pulmonary embolism, respectively. The preoperative symptoms and postoperative complications were all significantly improved in other 12 patients, and MRI showed no tumor recurrence. CONCLUSION: According to our experience, we recommend GTR as the primary goal, which is associated with improved rates of tumor control and without increasing rates of postoperative complications.
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Neoplasias do Plexo Corióideo/diagnóstico por imagem , Glioma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Terceiro Ventrículo/diagnóstico por imagem , Adulto , Idoso , Neoplasias do Plexo Corióideo/patologia , Neoplasias do Plexo Corióideo/cirurgia , Feminino , Seguimentos , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terceiro Ventrículo/patologia , Terceiro Ventrículo/cirurgiaRESUMO
CONTEXT: Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of coronary heart disease (CHD) in clinics. OBJECTIVE: This study evaluated the cardioprotective effects of NXT alone and in combination with ticagrelor (TIC) and atorvastatin (ATO). MATERIALS AND METHODS: Qi deficiency and blood stasis rats were established by 8 weeks high fat diet feeding and 16 days exhaustive swimming and randomly divided into seven groups, that is, NXT (250, 500 and 1000 mg/kg/d), TIC (20 mg/kg/d), ATO (8 mg/kg/d), NXT (500 mg/kg/d)+TIC (20 mg/kg/d) and NXT (500 mg/kg/d)+ATO (8 mg/kg/d) group, with oral administration for 12 weeks. The contents of TC, TG, LDL-C, HDL-C, IL-1ß, IL-6, IL-8, TNF-α, AST, ALT, SOD, MDA, CK-MB, LDH, TXA2, PGI2, IgA, IgG, IgM and C3 in serum were measured. RESULTS: NXT + TIC group was significantly superior to the TIC group in decreasing the levels of TC (4.34 vs. 5.54), TG (3.37 vs. 4.66), LDL-C (1.21 vs. 1.35), LDH (4919.71vs. 5367.19) and elevating SOD level (248.54 vs. 192.04). NXT + ATO group was significantly superior to the ATO group in decreasing the levels of AST (195.931 vs. 241.63), ALT (71.26 vs. 83.16), LDH (4690.05 vs. 5285.82), TXA2 (133.73 vs. 158.67), IgG (8.08 vs. 9.80), C3 (2.03 vs. 2.35) and elevating the levels of HDL-C (1.19 vs. 0.91), SOD (241.91vs. 209.49). CONCLUSIONS: The present findings demonstrate that the combined use of NXT with TIC and ATO had better integrated regulating effects than TIC and ATO, respectively. The mechanism of action requires further research.
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Atorvastatina/farmacologia , Cardiotônicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ticagrelor/farmacologia , Animais , Atorvastatina/administração & dosagem , Cardiotônicos/administração & dosagem , Doença das Coronárias/prevenção & controle , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Qi , Ratos , Ratos Sprague-Dawley , Ticagrelor/administração & dosagemRESUMO
Astrocytes have multiple functions in the brain, including affecting blood vessel (BV) homeostasis and function. However, the underlying mechanisms remain elusive. Here, we provide evidence that astrocytic neogenin (NEO1), a member of deleted in colorectal cancer (DCC) family netrin receptors, is involved in blood vessel homeostasis and function. Mice with Neo1 depletion in astrocytes exhibited clustered astrocyte distribution and increased BVs in their cortices. These BVs were leaky, with reduced blood flow, disrupted vascular basement membranes (vBMs), decreased pericytes, impaired endothelial cell (EC) barrier, and elevated tip EC proliferation. Increased proliferation was also detected in cultured ECs exposed to the conditioned medium (CM) of NEO1-depleted astrocytes. Further screening for angiogenetic factors in the CM identified netrin-1 (NTN1), whose expression was decreased in NEO1-depleted cortical astrocytes. Adding NTN1 into the CM of NEO1-depleted astrocytes attenuated EC proliferation. Expressing NTN1 in NEO1 mutant cortical astrocytes ameliorated phenotypes in blood-brain barrier (BBB), EC, and astrocyte distribution. NTN1 depletion in astrocytes resulted in BV/BBB deficits in the cortex similar to those in Neo1 mutant mice. In aggregate, these results uncovered an unrecognized pathway, astrocytic NEO1 to NTN1, not only regulating astrocyte distribution, but also promoting cortical BV homeostasis and function.