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1.
Artigo em Inglês | MEDLINE | ID: mdl-38567538

RESUMO

To reduce the cost of healthcare expenditures in China, the government has developed a centralised volume-based procurement (CVBP) policy for medicines and medical consumables. Based on tracking the development history of centralised procurement in China, this study explores China's CVBP model. By comparing the centralised procurement models and healthcare expenditure data among China, the United States (U.S), the United Kingdom (UK), and Singapore, we find that China still faces many challenges in implementing the CVBP policy. The main challenges are as follows. First, the policy cannot be guaranteed the effectiveness of implementation without a well-coordinated regulatory mechanism. Second, the CVBP rules and quality evaluation standards are imperfect. Third, the interests of healthcare companies cannot be guaranteed. Fourth, the policy affects the benefits of medical institutions, and the government has not built a compensation mechanism for medical institutions. Fifth, it poses a challenge to the operational capacity and innovation level of Chinese companies. Therefore, this paper posits a three-stage strategy and nine measures that could benefit China's progress in implementing the CVBP policy.

2.
Biochem Biophys Res Commun ; 644: 149-154, 2023 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-36652766

RESUMO

Doxorubicin (DOX) is extensively used for the treatment of kinds of cancers, and cardiovascular toxicity is one of the side effects. However, it is unclear whether DOX causes impairment of cardiac function by promoting atherosclerosis. Thus, we investigated the role of DOX in regulating the lipid deposition of macrophages and its molecular mechanism. RAW 264.7 cell line was stimulated with DOX in the presence or absence of low-density lipoprotein (LDL). We found that DOX increased miR-33 and reduced ATP binding cassette transporter A1 (ABCA1) protein. Moreover, cholesterol efflux was suppressed by DOX, which was more efficient under a high-cholesterol condition. After transfecting mimics or inhibitors of miR-33 into cells, ABCA1 protein was respectively decreased and increased, and intracellular lipid accumulation was correspondingly regulated. Overall, DOX suppresses the expression of ABCA1 protein by upregulating miR-33, promoting an intracellular lipid deposition in macrophages, which is a sign of early atherosclerosis. This provides new insights for clinical observation and evaluation of the side effects of DOX.


Assuntos
Aterosclerose , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Colesterol/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Aterosclerose/metabolismo , Doxorrubicina/farmacologia
3.
BMC Cancer ; 23(1): 95, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707772

RESUMO

OBJECTIVE: To evaluate the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) for primary cervical lymphoma (PCL), an extremely rare disease without treatment consensus. METHODS: We conducted a retrospective study included 177 patients, including 169 cases identified from literature review. The Kaplan-Meier methods and Cox regression were used to determine the OS, DSS, RFS, and relevant risk factors. RESULTS: The 5-year OS and 5-year DSS rates were 85.8 and 87.2%, respectively, while the 5-year RFS rate was 85.5%. Diffuse large B-cell lymphoma (DLBCL) was the predominant subtype that comprised 63.8% (113 cases) in this cohort. Multivariate analysis in the DLBCL subgroup revealed that age ≥ 60 years (Odds ratio [OR]: 26.324, 95% Confidence Interval [CI]: 5.090-136.144, P < 0.001) or stage IIIE-IVE (advanced stage) (OR: 4.219, 95%CI: 1.314-13.551, P = 0.016) were the risk factors for OS, while patients with age ≥ 60 years (OR:23.015, 95%CI: 3.857-137.324, P = 0.001), and stage IIIE-IVE (OR: 4.056, 95% CI: 1.137-14.469, P = 0.031) suffered a poor DSS. Chemotherapy and/or radiotherapy improved the OS (P = 0.008), DSS (P = 0.049), and RFS (P = 0.003). However, cancer-directed surgery did not improve the OS, DSS, and RFS. The risk factor was unavailable in other subtypes of PCL due to limited cases. CONCLUSION: The survival outcomes in patients with PCL at early stage were satisfactory, while the advanced disease stage and age ≥ 60 years were the two major factors predicting poor prognosis in DLBCL subtype.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Pessoa de Meia-Idade , Linfoma Difuso de Grandes Células B/patologia , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Langmuir ; 39(18): 6399-6405, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37105949

RESUMO

Ex-service SF6 adsorbents in SF6 gas-insulated electric equipment contain many toxic substances. Inside, HF and H2S are two typical toxic gases. Based on the first principle, the interaction process between HF/H2S and α-Al2O3 (0001) surfaces was calculated using the density functional theory (DFT). The results showed that the adsorption of HF on α-Al2O3 (0001) is stronger than that of H2S. Under the five adsorption sites, the adsorption effect of HF-H and HF-F was similar. At O-2 site, the adsorption energy of H2S-H adsorption configuration is significantly higher than that of the other four sites. The density of states (DOS) indicated that new peaks appeared after adsorption. The DOS and partial density of states (PDOS) indicated that the adsorption of HF and H2S occurs via chemical adsorption. The DOS and PDOS shifted to the right when the S atom was approaching, proving that the system shifts to instability. Compared with the energy gap of α-Al2O3 (0001), HF and H2S adsorption systems decreased significantly. The energy gap of the HF adsorption system was 1.173 eV larger than that of the H2S system and the geometry was relatively stable, which is consistent with the DOS and PDOS adsorption calculation results. Thus, the adsorption of HF and H2S on α-Al2O3 (0001) surfaces was clearly different. The findings of this study may provide theoretical guidance for the adsorption of other gases or developing a new adsorbent.

5.
Biochem Biophys Res Commun ; 573: 13-18, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34375764

RESUMO

AIMS: To assess the effects of a ketogenic diet on metabolism and renal fibrosis in spontaneously hypertensive rats. MATERIALS AND METHODS: Male spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were randomly divided into a ketogenic diet group and a normal diet group. Blood glucose and metabolites were measured after 4 weeks. Renal autophagy-related protein expression was detected by Western blot, and renal fibrosis was detected by Masson staining. RESULTS: Compared with the normal diet, the ketogenic diet led to significantly decreased glucose tolerance and metabolism; overactivated the renin-angiotensin-aldosterone system; and reduced renal autophagy-related protein expression in SHRs; Masson staining and other experiments showed that the ketogenic diet had no significant effect on hypertensive renal fibrosis. CONCLUSION: A Ketogenic diet could lead to disorders of glucose and lipid metabolism, increase hypertension by activating the RAAS, reduce renal autophagy levels and aggravate renal parenchymal damage. Therefore, a ketogenic diet, as a kind of natural therapy, should be vigilantly monitored to prevent further damage in patients with hypertension.


Assuntos
Autofagia/efeitos dos fármacos , Dieta Cetogênica/efeitos adversos , Nefropatias/induzido quimicamente , Doenças Metabólicas/induzido quimicamente , Insuficiência Renal/induzido quimicamente , Animais , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Wistar
6.
Microvasc Res ; 135: 104134, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33428882

RESUMO

BACKGROUND: Clinical data show that aneurysm rupture causes high mortality in aged men. MicroRNAs (miRNAs) were reported to regulate endothelial progenitor cells (EPCs) which play a vital role in repairing endothelial damage and maintaining vascular integrity. This study identified a novel miRNA regulator for the functions of EPCs in aneurysm repair. METHODS: Abdominal aortic aneurysm (AAA) model was established on Sprague-Dawley rats which later underwent antagomiR-222 treatment. The histopathological changes of AAA rats were examined by hematoxylin-eosin staining. Flow cytometry was performed to quantify EPCs in peripheral blood and identify EPCs isolated from the rat femur. The potential target of miR-222-3p was predicted by TargetScan v7.2 and validated by Dual-luciferase reporter assay. The effects of miR-222-3p and ADIPOR1 on the migration, invasion and tube formation of EPCs were evaluated by wound healing, Transwell and tube formation assays. The expressions of miR-222-3p and ADIPOR1 in aortic aneurysm tissues and EPCs were assessed by qRT-PCR or Western blot. RESULTS: AAA exhibited histopathological abnormality, a decreased number of EPCs in the peripheral blood and an increased miR-222-3p expression. AntagomiR-222 injection reversed all these phenomena in AAA rats. Upregulating miR-222-3p expression inhibited the migration, invasion, and tube formation of EPCs, and the expressions of ADIPOR1 and phosphorylated-AMKP, while downregulating miR-222-3p expression exerted opposite effects in EPCs. ADIPOR1 was identified as a target gene of miR-222-3p. Overexpressing ADIPOR1 abrogated the effects of miR-222-3p upregulation on EPCs. CONCLUSION: Downregulated miR-222-3p prompted the migration, invasion and recruitment of EPCs by targeting ADIPOR1-induced AMKP activation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Aorta Abdominal/enzimologia , Aneurisma da Aorta Abdominal/enzimologia , Movimento Celular , Células Progenitoras Endoteliais/enzimologia , MicroRNAs/metabolismo , Neovascularização Fisiológica , Receptores de Adiponectina/metabolismo , Animais , Antagomirs/genética , Antagomirs/metabolismo , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/patologia , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Células Progenitoras Endoteliais/patologia , Ativação Enzimática , Humanos , Masculino , MicroRNAs/genética , Fosforilação , Ratos Sprague-Dawley , Receptores de Adiponectina/genética , Transdução de Sinais
7.
Eur Radiol ; 31(11): 8364-8373, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33956177

RESUMO

OBJECTIVE: To explore the value of computed tomography perfusion (CTP) imaging for evaluating the efficacy of encephaloduroarteriosynangiosis (EDAS) treatment of moyamoya syndrome (MMS). METHODS: Forty-three patients with MMS (48 hemispheres) who received EDAS treatment were examined using CTP and DSA before and after surgery. CTP of the ipsilateral cortex, contralateral mirror area, and pons region were measured, and the relative cerebral blood flow (rCBF) and volume (rCBV), mean transit time (rMTT), and time-to-peak (rTTP) were calculated. Based on postoperative DSA, 48 hemispheres were apportioned to two groups based on rich (grades 2, 3) or poor (grades 0, 1) collateral vessel formation, and the pre- and post-operative differences in perfusion changes were compared. The association between clinical outcome, CTP, and the degree of DSA collateral vessels was explored. RESULTS: rCBF and rMTT significantly improved in both the poor and rich collateral vessel formation groups (n = 21 and 27, respectively), while rTTP significantly improved only in the latter. Postoperative CTP improved in the rich and the grade 1 collateral vessel groups (p < 0.01). The clinical improvement was consistent with the improvement of CTP (p = 0.07), but less consistent with the degree of collateral angiogenesis (p = 0.003). CONCLUSION: CTP can quantitatively evaluate the improvement of brain tissue perfusion in the operated area after EDAS. Brain tissue perfusion in operated areas improved regardless of postoperative rich or poor collateral vessel formation observed via DSA. A significant improvement in rTTP in the operated area may indicate the formation of abundant collateral vessels. KEY POINTS: • CTP showed that brain tissue perfusion in the operated area after EDAS improved regardless of rich or poor collateral vessel formation observed via DSA. • Significant improvement of rTTP in the operated area may indicate the formation of abundant collateral vessels.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Circulação Cerebrovascular , Humanos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Imagem de Perfusão , Tomografia Computadorizada por Raios X
8.
Eur Radiol ; 31(8): 5544-5551, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33564956

RESUMO

OBJECTIVE: To evaluate the feasibility of CT angiography (CTA) for assessing anterior choroidal artery (AChA) and posterior communicating artery (PComA) dilatation in patients with moyamoya syndrome (MMS). METHODS: Eighty-eight MMS patients who underwent digital subtraction angiography (DSA) and CTA within 1 month were enrolled. The AChA was graded using both DSA and CTA. Given the features of dual blood supply, DSA was firstly used for grading of the PComA. Then, the calibers of PComA, P1 or P2 segment of the posterior cerebral artery (PCA), were recorded from CTA. Taking DSA as a reference standard, the optimal cutoff values of the PComA/P1 or PComA/P2 were calculated to determine the dilatation of PComA. Both the AChA and PComA were classified as extreme dilatation (ED, grade 2) or non-extreme dilatation (NED, grade 0 or 1). RESULTS: The AChA was evaluated in 149 affected hemispheres of 88 patients while the PComA was evaluated in 70 affected hemispheres of 49 patients. The sensitivity and specificity of CTA in diagnosing AChA-ED were 92% and 93.5% respectively. Both the PComA/P1 (p < 0.001) and PComA/P2 (p = 0.4) ratios were increased in the PComA-ED group with the former yielding a better detecting performance than the latter (AUC = 0.92 vs 0.85, p = 0.046). When using 0.71 as a cutoff value, the sensitivity and specificity of the PComA/P1 ratio for diagnosis of PComA-ED cases were 91.3% and 83.3% respectively. CONCLUSIONS: CTA could be used for the AChA classification in MMS patients, while a PComA/P1 ratio greater than 0.71 indicates the existence of PComA-ED. KEY POINTS: • CTA showed a high sensitivity, specificity, and accuracy in diagnosing AChA-ED in patients with MMS. • PComA/P1 ratio greater than 0.71 on CTA signified an extremely dilated PComA. • CTA could be used to assess the dilatation of AChA and PComA in MMS patients, especially for routine postoperative follow-up.


Assuntos
Doença de Moyamoya , Angiografia Digital , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Dilatação , Humanos , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Artéria Cerebral Posterior/diagnóstico por imagem , Sensibilidade e Especificidade
9.
Biotechnol Lett ; 43(3): 745-755, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33386495

RESUMO

BACKGROUND: There is increasing evidence that circular RNA (circRNA) disorders have an impact on the progression of various malignancies. The expression characteristics, function and underlying mechanism of circ_0001247 in cervical cancer (CC) have not been confirmed. METHODS: GSE147483 datasets of circRNAs expression in CC cell line and normal cervical cell line were retrieved from GEO database, and the circRNA with significant difference was selected; circ_0001247, miR-1270, and Zinc finger E-box binding homeobox 2 (ZEB2) expressions in CC tissues and cell lines were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay; cell counting kit-8 (CCK-8) assay and BrdU assay were applied to monitor the proliferative ability of CC cells; Transwell assay was conducted to examine the migration and invasion of CC cells, and flow cytometry was used to evaluate the apoptosis; Western blot assay was adopted to detect ZEB2 protein expressions; dual-luciferase report gene assay was used to verify the targeting relationship between circ_0001247 and miR-1270, and miR-1270 and the 3'UTR of ZEB2. RESULTS: Analysis of GSE147483 suggested that circ_0001247 could probably be an oncogenic circRNA in CC. Compared with that in adjacent tissues and normal cervical epithelial cells, circ_0001247 expression in CC tissues and cell lines was significantly increased; knocking down circ_0001247 expression could inhibit the proliferation and metastasis of CC cells, and promote apoptosis, while circ_0001247 overexpression worked oppositely; circ_0001247 sponged miR-1270 in CC cells; miR-1270 diminished the promoting effect of circ_0001247 by inactivating the ZEB2. CONCLUSION: Circ_0001247 promotes progression of CC by sponging miR-1270 to upregulate ZEB2 expression level.


Assuntos
MicroRNAs/metabolismo , RNA Circular/metabolismo , Neoplasias do Colo do Útero , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Feminino , Humanos , MicroRNAs/genética , RNA Circular/genética , Transcriptoma/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética
10.
Cell Biochem Funct ; 38(5): 642-650, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32162707

RESUMO

Activated Cdc42-associated kinase 1 (ACK1) expression is upregulated in hepatocellular carcinoma (HCC) tissues and other tumour tissues. However, the function and regulatory mechanism of ACK1 in HCC remains unclear. In this study, the expression of pTyr284-ACK1, pSer473-AKT and PTEN in HCC was detected by immunohistochemistry, and its clinicopathological significance was analysed. Then, ACK1-targeted small molecule inhibitors AIM-100 and Dasatinib were used to treat cells SK-Hep-1 and HepG2, and changes in activity and biological behaviours of PTEN/AKT/mTOR signalling pathway were observed. The results showed that pTyr284-ACK1 protein was highly expressed in HCC tissues and was related to the poor prognosis of patients; the expression of pTyr284-ACK1 protein was positively correlated with pSer473-AKT and negatively correlated with PTEN. In addition, after treatment either with AIM-100 or Dasatinib, both proliferation of two cells and migration, invasion of SK-Hep-1 cells were all significantly inhibited. Meanwhile, ACK1, pTyr284-ACK1, pSer473-AKT, mTOR and EGFR were down-regulated; PTEN was up-regulated when analysed by western-blot in SK-Hep-1 cells. These results demonstrated that ACK1 may promote HCC development via PTEN/AKT/mTOR pathway. Targeted inhibition of ACK1 may be a novel therapeutic strategy for HCC. SIGNIFICANCE OF THE STUDY: Hepatocellular carcinoma (HCC) is a common malignant tumour with high mortality. Our study showed that ACK1 and pTyr284-ACK1 are highly expressed in HCC and may promote HCC development through the PTEN/AKT/mTOR signalling pathway. Targeted inhibition of ACK1 expression with small inhibitors AIM-100 and Dasatinib may weaken tumour cells ability of proliferation, migration and invasion. Our results suggested that downregulation of ACK1 may be a potential therapeutic strategy for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Carcinoma Hepatocelular/patologia , Ciclo Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/genética , Células Tumorais Cultivadas
11.
Gynecol Endocrinol ; 36(1): 49-54, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31269828

RESUMO

Chronic psychological stress has been considered to be a remarkable contributor to diminished ovarian reserve (DOR). However, there is a lack of a psychological stress-induced DOR animal model. We aim to validate the effects of an 8-week chronic unpredictable stress (CUS) paradigm on the ovarian reserve and reproductive hormone secretion of C57BL/6 mice. We found that after an 8-week CUS exposure, the numbers of primordial and preantral follicles and corpus luteum were significantly decreased in CUS model mice. Model mice also presented higher serum follicle-stimulating hormone, corticosterone levels and lower luteinizing hormone, estradiol, testosterone, anti-Müllerian hormone levels compared to those of control mice. Furthermore, we found that FSH receptor and AMH proteins were downregulated in model mouse ovaries. Although a significant litter size difference between the two groups was not found, the ovarian reserve remained significantly lower in the model group 6 weeks after CUS exposure. These results validated the hypothesis that the 8-week CUS paradigm that we adopted could induce the DOR phenotype in C57BL/6 mice and probably had a long-term adverse effect on ovarian reserve. Therefore, our results indicate that we have successfully established an animal model of psychological stress-induced DOR that can be used for further study.


Assuntos
Corpo Lúteo/patologia , Modelos Animais de Doenças , Tamanho da Ninhada de Vivíparos , Camundongos , Folículo Ovariano/patologia , Reserva Ovariana , Estresse Psicológico/patologia , Animais , Hormônio Antimülleriano/sangue , Doença Crônica , Corticosterona/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Ovário/metabolismo , Ovário/patologia , Receptores do FSH/metabolismo , Estresse Psicológico/sangue , Estresse Psicológico/metabolismo , Testosterona/sangue
12.
Immunol Cell Biol ; 97(8): 714-725, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30977930

RESUMO

Acute rejection is the major determinant for the long-term survival of donor liver after liver transplantation (LT). The aim of this study was to examine the therapeutic potential of interleukin (IL)-10-FasL-overexpressing immature dendritic cells (imDCs) to induce local immunosuppression in liver grafts. imDCs derived from donors were transduced by lentiviral vectors expressing human IL-10 and/or Fas ligand (FasL) gene(s), and the expression of surface molecules and the ability to induce T-cell proliferation were measured. imDCs were intraperitoneally injected into recipient rats as a model of LT to examine the rejection grade [Banff rejection activity index (RAI)], liver functions [Alanine aminotransferase, Aspartate aminotransferase (AST) and total bilirubin (TBIL)] and post-transplant survival. IL-10 and FasL co-transduction of imDCs induced a greater reduction in CD80, CD86 and major histocompatibility complex class II (MHC II) expression, as well as T-cell proliferation, but increased levels of IL-10 and FasL in culture supernatants compared with mono-transduced or untransduced imDCs (P < 0.05). The infusion of co-transduced imDCs in LT recipients reduced RAI scores, decreased plasma AST and TBIL, and prolonged survival compared with mono-transduced or untransduced imDC-treated liver allografts. These findings demonstrated that the transfusion of IL-10-FasL/imDCs enhanced immune tolerance and prolonged the survival of liver allografts after LT. The immunomodulatory activity of IL-10- and FasL-modified imDCs might be a new therapeutic approach to prevent organ rejection in clinical transplantation.


Assuntos
Células Dendríticas/transplante , Rejeição de Enxerto/prevenção & controle , Transplante de Fígado/efeitos adversos , Tolerância ao Transplante , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Proteína Ligante Fas/genética , Proteína Ligante Fas/imunologia , Proteína Ligante Fas/metabolismo , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-10/metabolismo , Masculino , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Transplante Heterotópico/efeitos adversos
13.
Sheng Li Xue Bao ; 71(2): 261-270, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31008485

RESUMO

It was reported that α7 nicotinic acetylcholine receptor (α7-nAChR) knockout (α7 KO) mice showed few functional phenotypes. The purpose of this study was to investigate the effect of α7 KO on the electrophysiological characteristics of hippocampus in mice. The effect of α7 KO on hippocampal CA3-CA1 synaptic transmission in mice was evaluated by standard extracellular field potential recordings. The electrophysiological phenotype of γ-aminobutyrate A receptors (GABAA-Rs) of single hippocampal neuron was detected by perforated patch-clamp recordings. The results showed that, the slope of field excitatory postsynaptic potential (fEPSP) and carbachol-induced theta oscillation were significantly decreased in the hippocampal CA1 neurons of α7 KO mice, compared with those of wild type mice. Under the treatment of GABAA-R agonist muscimol, the I-V curves of both the hippocampal CA1 and CA3 neurons of α7 KO mice shifted towards depolarizing direction obviously, compared with those of wild type mice. These results suggest that the hippocampal CA3-CA1 synaptic transmission in α7 KO mice was significantly impaired and GABAA-R maturation was significantly delayed, indicating that the deletion of α7-nAChR gene could significantly change the electrophysiological function of the hippocampus. The results may provide a new understanding of the role of α7-nAChR in hippocampal function and associated diseases.


Assuntos
Hipocampo/citologia , Neurônios/fisiologia , Transmissão Sináptica , Receptor Nicotínico de Acetilcolina alfa7/fisiologia , Animais , Camundongos , Camundongos Knockout , Fenótipo
14.
J Transl Med ; 16(1): 337, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514296

RESUMO

BACKGROUND: Temporal lobe epilepsy (TLE) is a common and often refractory brain disease that is closely correlated with inflammation. Alpha-methyl-L-tryptophan (AMT) is recognized as a surrogate marker for epilepsy, characterized by high uptake in the epileptic focus. There are many advantages of using the magnetic targeting drug delivery system of superparamagnetic iron oxide nanoparticles (SPIONs) to treat many diseases, including epilepsy. We hypothesized that AMT and an IL-1ß monoclonal antibody (anti-IL-1ß mAb) chelated to SPIONs would utilize the unique advantages of SPIONs and AMT to deliver the anti-IL-1ß mAb across the blood-brain barrier (BBB) as a targeted therapy. METHODS: Acute TLE was induced in 30 rats via treatment with lithium-chloride pilocarpine. The effects of plain-SPIONs, anti-IL-1ß-mAb-SPIONs, or AMT-anti-IL-1ß-mAb-SPIONs on seizure onset were assessed 48 h later. Perl's iron staining, Nissl staining, immunofluorescence staining and western blotting were performed after magnetic resonance imaging examination. RESULTS: The imaging and histopathology in combination with the molecular biology findings showed that AMT-anti-IL-1ß-mAb-SPIONs were more likely to penetrate the BBB in the acute TLE model to reach the targeting location and deliver a therapeutic effect than plain-SPIONs and anti-IL-1ß-mAb-SPIONs. CONCLUSIONS: This study demonstrated the significance of anti-IL-1ß-mAb treatment in acute TLE with respect to the unique advantages of SPIONs and the active location-targeting characteristic of AMT.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Epilepsia do Lobo Temporal/tratamento farmacológico , Interleucina-1beta/imunologia , Nanopartículas de Magnetita/química , Triptofano/análogos & derivados , Doença Aguda , Animais , Epilepsia do Lobo Temporal/patologia , Proteína Glial Fibrilar Ácida/metabolismo , Inflamação/patologia , Imageamento por Ressonância Magnética , Masculino , Ratos Sprague-Dawley , Fator de Transcrição RelA/metabolismo , Triptofano/química
15.
Artigo em Inglês | MEDLINE | ID: mdl-29790192

RESUMO

BACKGROUND: The understanding of spontaneous scar-based reentrant atrial arrhythmia is limited. We aim to characterize the electrophysiologic and mapping features of spontaneous scar-based atrial flutter (AFL) and outcomes of catheter ablation. METHODS: Consecutive patients with a diagnosis of AFL who underwent catheter ablation from January 2012 to June 2015 were screened. Scars were detected in 12 patients and were included in this study. All had negative coronary angiography. These patients were divided into right AFL (seven patients) and left AFL groups (five patients) based on electrophysiologic mappings. RESULTS: Compared to patients with right AFL, the size of right atrium (RA) was smaller and left atrium (LA) was larger in the left AFL group. The proportion of the scar area was 11.1 ± 11.7 % in the RA AFL group and 7.8 ± 2.8 % in the LA AFL group. The difference was significant (P = 0.001). The acute success rates of ablation were 85.7% and 100%, respectively, in patients with right and left AFL (P = 0.304). During the follow-up, expansion of the scar area was noted in three patients with recurrent right AFL. No scar expansion was noted in one patient with recurrent left AFL. In addition, three patients with right AFL required permanent pacemaker implantation for sinus node dysfunction, and no one required pacemaker in patients with left AFL. CONCLUSIONS: Spontaneous scar could serve as substrate for AFL in RA or LA. Compared to left AFL, there was a higher rate of recurrence and pacemaker implantation in patients with right AFL.

16.
Childs Nerv Syst ; 34(6): 1189-1197, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29374799

RESUMO

OBJECTIVE: Vascular and hemodynamic changes were not consistent in symptomatic and non-symptomatic cerebral hemisphere in patients with symptomatic moyamoya syndrome (MMS). Thus, the purpose of this study is to evaluate the hemodynamic difference between symptomatic and non-symptomatic cerebral hemisphere in patients with symptomatic MMS. METHODS: Patients who were diagnosed with symptomatic MMS were retrospectively collected. All cases underwent CTP examination. Regions of interest (ROIs) were chosen in the mirroring bilateral frontal lobes, temporal lobes, the basal ganglia, and the brainstem as control region. The relative perfusion parameter values of symptomatic side were compared with non-symptomatic side. RESULTS: Of the 40 patients, 33 patients were taken into assessment. In all cases (n = 33), rCBF, rMTT, and rTTP in all regions of interest (ROIs) of the symptomatic side were significantly different from those of contralateral side. In unilateral MMS patients (n = 7), rCBF values were not significantly different between two sides in the temporal lobe and basal ganglia area; rTTP values were significantly higher in the symptomatic side. rMTT values were significantly higher only in the temporal lobe of symptomatic side. In bilateral MMS patients (n = 26), rCBF and rMTT in all ROIs of the symptomatic side were significantly different from those of contralateral side. However, there were no significant differences between two sides in all ROIs on rTTP values. CONCLUSIONS: This study demonstrates that rCBF and rMTT were more sensitive than rTTP for evaluating hemodynamic changes in patients with symptomatic bilateral MMS. Furthermore, patients with unilateral MMS may have a preserved rCBF compared to those with bilateral disease.


Assuntos
Hemodinâmica/fisiologia , Doença de Moyamoya/fisiopatologia , Adulto , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
17.
Int Heart J ; 59(1): 71-76, 2018 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-29269710

RESUMO

Discrimination between atrioventricular node reentry tachycardia (AVNRT) and orthodromic reciprocating tachycardia (ORT) during an electrophysiological study is sometimes challenging. This study aimed to investigate if the difference in the local VA (ventricle-atrium) interval during ventricular entrainment pacing and during tachycardia (DVA, defined as the shortest local VA interval of coronary sinus [CS] during entrainment minus the shortest local VA interval of CS during tachycardia) was different in patients with AVNRT and patients with ORT.Diagnoses of AVNRT or ORT through a concealed accessory pathway (AP) were made according to conventional electrophysiological criteria and ablation results. Entrainment by right ventricular (RV) pacing was performed in each patient before ablation and patients with successful entrainment were included in the study. The DVA was compared between patients with AVNRT and patients with ORT. The DVA in patients with AVNRT was significantly longer than that in patients with ORT (120 ± 20 versus 5.7 ± 9; P < 0.001). In each patient with AVNRT of slow-fast type, fast-slow type, and slow-slow type, the DVA was more than 48 ms. In each patient with ORT using a left free wall accessory pathway (AP), right free wall AP, and septal AP, the DVA was less than 20 ms.DVA was found to be a rapid, useful test in distinguishing patients with AVNRT from those with ORT.


Assuntos
Nó Atrioventricular/fisiopatologia , Técnicas Eletrofisiológicas Cardíacas/métodos , Sistema de Condução Cardíaco/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia por Reentrada no Nó Sinoatrial/diagnóstico , Adulto , Ablação por Cateter/métodos , Diagnóstico Diferencial , Feminino , Sistema de Condução Cardíaco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Taquicardia por Reentrada no Nó Sinoatrial/fisiopatologia , Taquicardia por Reentrada no Nó Sinoatrial/cirurgia
18.
Molecules ; 22(12)2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29186052

RESUMO

Intelligent optimization algorithms have advantages in dealing with complex nonlinear problems accompanied by good flexibility and adaptability. In this paper, the FCBF (Fast Correlation-Based Feature selection) method is used to filter irrelevant and redundant features in order to improve the quality of cancer classification. Then, we perform classification based on SVM (Support Vector Machine) optimized by PSO (Particle Swarm Optimization) combined with ABC (Artificial Bee Colony) approaches, which is represented as PA-SVM. The proposed PA-SVM method is applied to nine cancer datasets, including five datasets of outcome prediction and a protein dataset of ovarian cancer. By comparison with other classification methods, the results demonstrate the effectiveness and the robustness of the proposed PA-SVM method in handling various types of data for cancer classification.


Assuntos
Inteligência Artificial , Neoplasias/diagnóstico , Máquina de Vetores de Suporte , Algoritmos , Bases de Dados Factuais , Humanos , Reprodutibilidade dos Testes
19.
Eur Radiol ; 26(1): 254-61, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25925360

RESUMO

PURPOSE: To evaluate the utility of CT perfusion (CTP) for the assessment of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis in patients with Moyamoya syndrome (MMS). SUBJECTS AND METHODS: Twenty-four consecutive MMS patients, who underwent unilateral STA-MCA bypass surgery, received CTP before and after surgery. The relative perfusion parameter values of surgical hemispheres before treatment were compared with post-treatment values. All patients underwent CT angiography (CTA) before and after surgery in order to confirm the patency of bypass. RESULTS: The follow-up CTA after surgery clearly demonstrated 20 (20/24, 83.3 %) bypass arteries, whereas four (16.7 %) bypass arteries were occluded or very small. Postoperative rMTT and rTTP values (P < 0.05) of the surgical side were significantly lower than pre-operation. In patients (n = 20) with bypass patency, postoperative rCBF, rMTT and rTTP values (P < 0.05) of the surgical side were significantly improved. However, the differences of all parameters were not significant (P > 0.05) in the patients (n = 4) without bypass patency after revascularization. CONCLUSION: This study demonstrates that CTP can provide a crucial quantitative assessment of cerebral haemodynamic changes in MMS before and after STA-MCA anastomosis. KEY POINTS: Twenty-four MMS patients undergoing STA-MCA bypass received CTP pre- and post-surgery. Cerebral haemodynamics improved on the surgical side post-surgery on CTP maps. rCBF might have a better correlation with patency of the bypass artery. CTP can evaluate cerebral perfusion changes in MMS patients after cerebral revascularization.


Assuntos
Revascularização Cerebral/métodos , Artéria Cerebral Média/diagnóstico por imagem , Doença de Moyamoya/diagnóstico por imagem , Artérias Temporais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/cirurgia , Perfusão , Período Pós-Operatório
20.
Neural Plast ; 2016: 2412958, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26925269

RESUMO

Purpose. Although active targeting of drugs using a magnetic-targeted drug delivery system (MTDS) with superparamagnetic iron oxide nanoparticles (SPIONs) is a very effective treatment approach for tumors and other illnesses, successful results of drug-resistant temporal lobe epilepsy (TLE) are unprecedented. A hallmark in the neuropathology of TLE is brain inflammation, in particular the activation of interleukin-1ß (IL-1ß) induced by activated glial cells, which has been considered a new mechanistic target for treatment. The purpose of this study was to determine the feasibility of the functionalized SPIONs with anti-IL-1ß monoclonal antibody (mAb) attached to render MRI diagnoses and simultaneously provide targeted therapy with the neutralization of IL-1ß overexpressed in epileptogenic zone of an acute rat model of TLE. Experimental Design. The anti-IL-1ß mAb-SPIONs were studied in vivo versus plain SPIONs and saline. Lithium-chloride pilocarpine-induced TLE models (n = 60) were followed by Western blot, Perl's iron staining, Nissl staining, and immunofluorescent double-label staining after MRI examination. Results. The magnetic anti-IL-1ß mAb-SPION administered intravenously, which crossed the BBB and was concentrated in the astrocytes and neurons in epileptogenic tissues, rendered these tissues visible on MRI and simultaneously delivered anti-IL-1ß mAb to the epileptogenic focus. Conclusions. Our study provides the first evidence that the novel approach enhanced accumulation and the therapeutic effect of anti-IL-1ß mAb by MTDS using SPIONs.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/tratamento farmacológico , Hipocampo/diagnóstico por imagem , Interleucina-1beta/antagonistas & inibidores , Nanopartículas de Magnetita/administração & dosagem , Animais , Astrócitos/metabolismo , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/imunologia , Hipocampo/metabolismo , Hipocampo/patologia , Interleucina-1beta/imunologia , Imageamento por Ressonância Magnética , Neurônios/metabolismo , Pilocarpina , Ratos , Ratos Sprague-Dawley
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