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1.
World J Gastroenterol ; 30(2): 158-169, 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38312121

RESUMO

BACKGROUND: Tumor budding (TB) has emerged as a promising independent prognostic biomarker in colorectal cancer (CRC). The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC. However, existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies. Consequently, this study investigated the correlation among TB categories, clinicopathological features, and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification. AIM: To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC. METHODS: The clinical data of 547 CRC patients were collected for this retrospective study. Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines. RESULTS: Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy (P = 0.004), clinical stage IV (P < 0.001), ≥ 4 regional lymph node metastases (P = 0.004), left-sided colonic cancer (P = 0.040), and Bd 2-3 (P = 0.002) were independent prognostic factors in patients with stage III-IV CRC. Moreover, the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3, both in the tumor stroma and its invasive margin. CONCLUSION: TB has an independent predictive prognostic value in patients with stage III-IV CRC. It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Prognóstico , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Colorretais/patologia , Neoplasias do Colo/patologia
2.
Nat Commun ; 15(1): 453, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212316

RESUMO

With the rapid development of nuclear energy, problems with uranium supply chain and nuclear waste accumulation have motivated researchers to improve uranium separation methods. Here we show a paradigm for such goal based on the in-situ formation of π-f conjugated two-dimensional uranium-organic framework. After screening five π-conjugated organic ligands, we find that 1,3,5-triformylphloroglucinol would be the best one to construct uranium-organic framework, thus resulting in 100% uranium removal from both high and low concentration with the residual concentration far below the WHO drinking water standard (15 ppb), and 97% uranium capture from natural seawater (3.3 ppb) with a record uptake efficiency of 0.64 mg·g-1·d-1. We also find that 1,3,5-triformylphloroglucinol can overcome the ion-interference issue such as the presence of massive interference ions or a 21-ions mixed solution. Our finds confirm the superiority of our separation approach over established ones, and will provide a fundamental molecule design for separation upon metal-organic framework chemistry.

3.
J Cell Biochem ; 125(3): e30524, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38226453

RESUMO

Pro-inflammatory microglia mainly rely on glycolysis to maintain cytokine production during ischemia, accompanied by an increase in inducible nitric oxide synthase (iNOS) and monocarboxylate transporter 1 (MCT1). The role of energy metabolism in the pro-inflammatory response of microglia is currently unclear. In this study, we tested the response of microglia in mice after cerebral ischemia and simulated an energy environment in vitro using low glucose culture medium. The research results indicate that the expression levels of iNOS and arginase 1 (ARG1) increase in the ischemic mouse brain, but the upregulation of MCT1 expression is mainly present in iNOS positive microglia. In microglia exposed to low glucose conditions, iNOS and MCT1 levels increased, while ARG1 levels decreased. Under the same conditions, knocking down MCT1 in microglia leads to a decrease in iNOS levels, while overexpression of MCT1 leads to the opposite result. The use of NF-κB inhibitors reduced the expression levels of iNOS and MCT1 in microglia. In summary, our data indicate that pyruvate maintains and enhances the NF-κB regulated pro-inflammatory response of microglia induced by low glucose.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Camundongos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Microglia/metabolismo , Ácido Pirúvico/metabolismo , Acidente Vascular Cerebral/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Isquemia Encefálica/metabolismo
4.
J Agric Food Chem ; 72(5): 2512-2525, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38286814

RESUMO

As part of a program to discover novel succinate dehydrogenase inhibitor fungicides, a series of new pyrazole acyl(thio)urea compounds containing a diphenyl motif were designed and synthesized. Their structures were confirmed by 1H NMR, HRMS, and single X-ray crystal diffraction analysis. Most of these compounds possessed excellent activity against 10 fungal plant pathogens at 50 µg mL-1, especially against Rhizoctonia solani, Alternaria solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Cercospora arachidicola. Interestingly, compounds 3-(difluoromethyl)-1-methyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9b, EC50 = 0.97 ± 0.18 µg mL-1), 1,3-dimethyl-N-((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1H-pyrazole-4-carboxamide (9a, EC50 = 2.63 ± 0.41 µg mL-1), and N-((4'-chloro-[1,1'-biphenyl]-2-yl)carbamoyl)-1,3-dimethyl-1H-pyrazole-4-carboxamide (9g, EC50 = 1.31 ± 0.15 µg mL-1) exhibited activities against S. sclerotiorum that were better than the commercial fungicide bixafen (EC50 = 9.15 ± 0.05 µg mL-1) and similar to the positive control fluxapyroxad (EC50 = 0.71 ± 0.11 µg mL-1). These compounds were not significantly phytotoxic to monocotyledonous and dicotyledonous plants. Structure-activity relationships (SAR) are discussed by substituent effects/molecular docking, and density functional theory analysis indicated that these compounds are succinate dehydrogenase inhibitors.


Assuntos
Compostos de Bifenilo , Fungicidas Industriais , Succinato Desidrogenase , Ureia , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Fungicidas Industriais/química , Pirazóis/química , Antifúngicos/farmacologia
5.
Int J Neurosci ; : 1-11, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37965801

RESUMO

AIMS: Based on our previous research on the specific miRNAs identified from Gastrodia elata, we selected Gas-miR2-3p to investigate its effects on neuroinflammation via in vitro and in vivo experiments. RESULTS: RT-qPCR analysis indicated that G. elata specific Gas-miR2-3p was detected in all murine tissues post-oral administration, suggesting their potential as orally bioavailable miRNA. The analysis of RT-qPCR, Western blotting and ELISA assays consistently demonstrate that the expression of inflammatory factors as TNF-α, IL-6, IL-1ß was decreased and the expression levels of p-p65 and p-IκBα were downregulated after the action of Gas-miR2-3p in both cell and animal experiments. CONCLUSION: Gas-miR2-3p can attenuate neuroinflammation by regulating the inflammation factors and suppressing the activation of the NF-κB signaling pathway. Our findings indicate that G. elata miRNAs, as novel active components, perform a modulatory role in the NF-κB signaling pathway associated with neuroinflammation in a cross-species way.

6.
Nano Lett ; 23(17): 8013-8021, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37615624

RESUMO

The rapid proliferative biological behavior of primary foci of anaplastic thyroid cancer (ATC) makes it a lethal tumor. According to the specific iodine uptake capacity of thyroid cells and enhanced endocytosis of ATC cells, we designed a kind of nanoclay drug-loading system and showed a promising treatment strategy for ATC. Introducing potassium iodide (KI) improves the homoaggregation of clay nanoparticles and then affects the distribution of nanoparticles in vivo, which makes KI@DOX-KaolinMeOH enriched almost exclusively in thyroid tissue. Simultaneously, the improvement of dispersibility of KI@DOX-KaolinMeOH changes the target uptake of ATC cells by improving the endocytosis and nanoparticle-induced autophagy, which regulate the production of autolysosomes and autophagy-enhanced chemotherapy, eventually contributing to a tumor inhibition rate of more than 90% in the primary foci of ATC. Therefore, this facile strategy to improve the homoaggregation of nanoclay by introducing KI has the potential to become an advanced drug delivery vehicle in ATC treatment.


Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Iodeto de Potássio/farmacologia , Iodeto de Potássio/uso terapêutico , Caulim , Endocitose , Sistemas de Liberação de Medicamentos , Neoplasias da Glândula Tireoide/tratamento farmacológico
7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1020002

RESUMO

Objective:To investigate the efficacy and cognitive function of 3 new antiepileptic drugs Oxcarbazepine (OXC), Lamotrigine (LTG) and Levetiracetam (LEV) in children with self-limited epilepsy with centrotemporal spikes (SeLECTS).Methods:This was a prospective study.A total of 98 children with SeLECTS who were treated in the Second Affiliated Hospital of Xinxiang Medical University from January 2014 to June 2020 were divided into OXC group, LTG group and LEV group according to the applied therapeutic drugs.Video electroencephalograph (EEG), Wechsler Intelligence Scale for Children (WISC) and event-related potentials (ERPs) of the children were collected before treatment and 48 weeks of treatment.Clinical efficacy and impact on cognitive function among the 3 groups were compared.Results:(1)Efficacy: There was no significant difference in the effective rate of seizure reduction after treatment among the 3 groups( χ2=0.808, P=0.668). There was no significant difference in EEG remission rate among the 3 groups( χ2=0.763, P=0.683). (2)Cognitive function: ①Intragroup comparison of WISC findings showed that the full scale score (FIQ) and verbal intelligence quotient (VIQ) were significantly enhanced, and the scores of comprehension, vocabulary, arithmetic, decoding and spelling subtests were more significantly enhanced in OXC group after treatment (all P<0.05). In the LTG group, FIQ, VIQ and operational intelligence quotient (PIQ) were significantly enhanced after treatment (all P<0.05), and the subtest scores of comprehension, vocabulary, arithmetic, mapping and layout were significantly enhanced (all P<0.05). In LEV group, FIQ, VIQ and PIQ were significantly enhanced after treatment (all P<0.05), especially the increase in the VIQ, and the scores of vocabulary, understanding, similarity, arithmetic, decoding and puzzle subtests were significantly enhanced (all P<0.05). Pairwise comparison of WISC findings showed that there were no significant differences in the FIQ, VIQ, PIQ and subtest scores before treatment among the 3 groups (all P>0.05). After treatment, the arithmetic and decoding scores of OXC group were significantly higher than those of LTG group (all P<0.05), which were comparable between OXC group and LEV group (all P>0.05). The PIQ and the scores of mapping and layout in LTG group were significantly higher than those of the other 2 groups (all P<0.05). The LEV group had higher scores in vocabulary, comprehension and spelling than those of the other 2 groups (all P<0.05), which had higher decoding scores than those of the LTG group (all P<0.05). No significant differences were found in decoding scores between LEV and OXC group (all P>0.05). Higher VIQ and FIQ were detected in LEV group than those of the other 2 groups (all P<0.05). ②Intragroup comparison of ERPs showed that the latency of LEV group after treatment was significantly shorter than that before treatment ( P<0.05), and there was no significant difference between the other 2 groups before and after treatment (all P>0.05). Pairwise comparison of ERPs showed that before treatment, there were no significant differences in P300 amplitude and latency among the 3 groups (all P>0.05). After treatment, the latency of LEV group was significantly shorter than that of the other 2 groups ( P<0.05), and there was no significant difference in the amplitude between the 3 groups before and after treatment ( P>0.05). Conclusions:(1)In the treatment of SeLECTS in children, OXC, LTG and LEV have reliable and equivalent effects.(2)OXC, LTG and LEV have protective effects on cognitive function in children with SeLECTS.After treatment, LEV provides the strongest protective effect on FIQ, and the protective effect on VIQ is equivalent to OXC, but better than LTG.LTG is superior in protecting spatial perception and PIQ.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-932960

RESUMO

Objective:To explore the correlation between tumor markers and prognosis of patients with idiopathic inflammatory myopathy (IIM) associated interstitial lung disease (ILD).Methods:A total of 149 patients who were no less than 18 years old and diagnosed with IIM-ILD from July 2017 to September 2019 in the First Affiliated Hospital of Zhengzhou University were consecutively enrolled in the study. Ten patients were lost to follow-up. The remaining 139 cases were regarded as research objects. Patients were divided into survival group or death group according to their one-year survival status. Then their baseline characteristics were compared. Univariate Cox regression analyses of age, gender, cancer, inflammatory indexes, muscle zymogram, tumor markers, ferritin, melanoma differentiation-associated gene 5 (MDA5) antibody and treatment regimens were conducted to identify prognostic risk factors of one-year mortality. Corrected multivariable cox regression was applied to screen the independent risk factors associated with one-year mortality of IIM-ILD. According to the cut-off value of carcinoembryonic antigen (CEA) and neuron specific enolase (NSE) (6 μg/L and 28 μg/L, respectively), patients were divided into high-level groups and low-level groups. Kaplan Meier survival curve were generated to compare one-year survival rate of high-level groups and low-level groups. On the basis of qualitative results of MDA5 antibody, patients were split into two groups with positive MDA5 antibody or negative MDA5 antibody. The differences of CEA, NSE levels between the two groups and the correlation between CEA, NSE levels and ferritin were analyzed.Results:Age, lactate dehydrogenase (LDH), CEA, carbohydrate antigen (CA) 199, NSE and ferritin in the death group were higher than those in the survival group, while the rate of immunosuppressant administration was lower than that in survival group ( P<0.05). Univariate regression analyses showed that CEA, cytokeratin 19 fragment (CYFRA211) and NSE were risk factors for one-year mortality of IIM-ILD. Adjusted by age, treatment regimens and tumor, multivariate regression analysis showed that CEA [ HR=1.112, 95% CI (1.017-1.214), P=0.019] and NSE [ HR=1.033, 95% CI (1.002-1.064), P=0.034] were independent risk factors for one-year mortality. One-year survival rate of the group with CEA≥6 μg/L was lower than that in the group with CEA<6 μg/L (Logrank test, P<0.001). Similarly, one-year survival rate of the group with NSE≥28 μg/L was lower than that in the group with NSE<28 μg/L (Logrank test, P<0.001). In addition, the CEA level in patients with positive MDA5 antibody was higher than that in patients with negative MDA5 antibody ( P<0.001). However, there was no correlation between NSE and MDA5 antibody. Moreover, serum levels of CEA ( r=0.299, P=0.002) and NSE ( r=0.349, P<0.001) were positively correlated with ferritin. Conclusions:Tumor markers have predictive value for the prognosis of IIM-ILD. Higher CEA and NSE are independent risk factors for poor prognosis in patients with IIM-ILD.

9.
Chinese Journal of Geriatrics ; (12): 1333-1336, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-957382

RESUMO

Objective:To assess the clinical efficacy of low-level laser therapy(LLLT)for the treatment of burning mouth syndrome(BMS)in elderly patients.Methods:As a randomized controlled study, 60 elderly BMS patients treated in the department of stomatology of Beijing Hospital from September 2018 to August 2021 were randomly divided into a laser group and a control group, including 7 man and 53 women, with an average age of(68.27±6.38)years.Patients in the laser group were treated with LLLT, and patients in the control group were treated with non-energy red light and oryzanol.The visual analogue scale and self-rating anxiety and depression scale were used to evaluate the two groups of patients.Results:After LLLT, the effectiveness rate of the laser group was 86.67%(26/30)on the 28th and 90th day, which was significantly higher than 63.33%(19/30)of the control group( χ2=4.356, P=0.037). When data for pre-treatment, the 28th day after treatment and the 90th day after treatment for the laser group were compared, results showed that after LLLT, pain symptoms of BMS patients were relieved and it lasted for some time, and anxiety and depression also improved, but there were episodes of relapse as time went on.Visual analogue scale and self-rating anxiety scores and depression scale scores of BMS patients for pre-treatment, the 28th and 90th days after treatment in the two groups were compared.Only self-rating anxiety scale scores of the laser group was lower than those of the control group on the 28th day, with statistical significance( t=2.622, P=0.011), indicating that LLLT could alleviate anxiety for BMS patients in the short term, but had no significant effect on patient depression.However, in the long term, LLLT had no significant effect on relieving anxiety and depression. Conclusions:LLLT has a certain effect on improving pain symptoms and anxiety in elderly BMS patients.

10.
Molecules ; 28(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36615249

RESUMO

Natural products are a source for pesticide or drug discovery. In order to discover lead compounds with high fungicidal or herbicidal activity, new niacinamide derivatives derived from the natural product niacinamide, containing chiral flexible chains, were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR and HRMS analysis. The fungicidal and herbicidal activities of these compounds were tested. The fungicidal activity results demonstrated that the compound (S)-2-(2-chloronicotinamido)propyl-2-methylbenzoate (3i) exhibited good fungicidal activity (92.3% inhibition) against the plant pathogen Botryosphaeria berengriana at 50 µg/mL and with an EC50 of 6.68 ± 0.72 µg/mL, which is the same as the positive control (fluxapyroxad). Compound 3i was not phytotoxic and could therefore be used as a fungicide on crops. Structure-activity relationships (SAR) were studied by molecular docking simulations with the succinate dehydrogenase of the fungal mitochondrial respiratory chain.


Assuntos
Fungicidas Industriais , Herbicidas , Praguicidas , Praguicidas/farmacologia , Niacinamida/farmacologia , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Fungicidas Industriais/química , Herbicidas/farmacologia , Estrutura Molecular
11.
Acta Anatomica Sinica ; (6): 288-294, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1015337

RESUMO

Objective To testify the link between the increase of inducible nitric oxide synthase (iNOS) and monocarboxylate transporter 1 (MCT1) expression in the M1 phenotype microglia under ischemic condition. Methods Photothrombosic ischemia stroke model was applied in 6 mice. BV2 cells were treated with low glucose medium contained 5mmol/L glucose for 2 hours. Immunofluorescent staining and Western blotting were used to check the responses from microglia in the mouse brains subjected to ischemia and BV2 cells were treated with low-glucose treatment. Application of RNA interference or plasmid transfection were used to regulate the MCT1 expression in BV2 cells. Results The expression levels of iNOS, MCT1 and arginase-1 (ARG1) increased in the ischemic side compared to the non-ischemic side of mice brain(P<0.01). In the BV2 cells exposed to low-glucose condition, iNOS and MCT1 levels increased(P<0.001), whereas ARG1 level decreased(P<0.01). RNA interference interfered the expression of MCT1 and then decreased the iNOS expression(P<0.01), while overexpression of MCT1 through plasmid transfection increased iNOS expression(P<0.01), while the ARG1 expressions in both conditions were not changed significantly. Conclusion After microglia polarized into inflammatory phenotype during ischemia period, iNOS production is related with MCT1 expression, and MCT1 is in the upstream of iNOS pathway.

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1015741

RESUMO

Genipin (Gen) is an important antioxidant that plays a crucial role in the process of intracellular resistance to oxidative stress. In order to study the effect of genipin on MIN6 cells injured by high glucose, the CCK-8 method was used to detect the cell survival rate. The cell viability of the high-glucose injury group decreased (P <0. 05). But after genipin acted on the cells injured by high glucose, the cell viability increased (P <0. 05). The mouse insulin detection kit and ATP content detection kit found that the insulin release in the high glucose injury group decreased (P < 0. 001) and the ATP content decreased (P <0. 001). After genipin was given, the insulin release increased (P <0. 01), ATP content increased (P <0. 01). The fluorescent probe DCFH-DA detected the intracellular reactive oxygen species (ROS) level and found that the ROS content in the high glucose-injury group was significantly increased (P <0. 01). After genipin was administered, ROS content decreased (P < 0. 05). Glutathione(GSH) / oxidized glutathione (GSSG), intracellular malondialdehyde (MDA), superoxide dismutase(SOD) and catalase (CAT) and lactate dehydrogenase (LDH) activity in the cell supernatant revealed that the GSH / GSSH ratio, SOD and CAT levels in the high glucose injury group decreased (P <0. 05), and the intracellular MDA and LDH levels were significant increased (P<0. 001) .After administration of genipin, the GSH / GSSH ratio, SOD and CAT levels increased (P <0. 01), MDA and LDH levels were significantly reduced (P <0. 01). Mitochondrial membrane potential (MMP) levels decreased in the highglucose injury group (P <0. 01). After genipin acted on the cells injured by high glucose, the MMP level increased (P < 0. 05). Western blot detected uncoupling protein 2 (UCP2), antioxidative proteinsglutathione reductase (GR) and glutaredoxin 1 (Grx1) contents. The results showed that UCP2 contents in the high glucose injury group increased (P <0. 01) and the content of oxidized protein decreased (P < 0. 01). After genipin was administered, the expression of UCP2 decreased (P < 0. 05), and the expression of antioxidative protein increased (P < 0. 05). Experiments suggest that genipin has anantioxidant protective effect on MIN6 cells damaged by high glucose and maintains the function of MIN6cells to promote insulin secretion. This experiment provides experimental data for the antioxidation of genipin on MIN6 cells injured by high glucose, and also provides new ideas for the follow-up study of genipin in the treatment and prevention of diabetes.

13.
Journal of Medical Biomechanics ; (6): E208-E215, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-904388

RESUMO

Objective To analyze the biomechanical characteristics of lumbar fusion by 3 internal fixation methods using three-dimensional (3D) finite element (FE) method. Methods The FE fixation models of physiological L4-5, unfixed fusion L4-5, translaminar facet screw (TLFS), lumbar pedical screw+translaminar facet screw (LPS+TLFS), bilateral pedical screw (BPS) with complete osteotomy or partial osteotomy of facet joint were established, respectively. The biomechanical characteristics of L4 centrum and implants under six motion states (spinal flexion, extension, lateral bending and axial rotation) in L4-5 fusion model and three fixation models were compared by FE analysis. Results The average maximal displacements of L4 centrum in L4-5 unfixed fusion model, TLFS model, TLFS+LPS model, BPS model were 1.410 8, 0.629 8, 0.336 9, 0.252 8 mm (complete osteotomy of facet joint) and 1.296 7, 0.844 9, 0.340 9, 0.273 8 mm (partial osteotomy of facet joint); the average maximal displacements of cage were 0.479 9, 0.319 5, 0.167 6, 0.126 4 mm (complete osteotomy of facet joint) and 0.378 7, 0.348 4, 0.183 5, 0.137 2 mm (partial osteotomy of facet joint);the average maximum stresses of screws and rods during 6 motions in TLFS model, TLFS+LPS model, BPS model were 178.34, 79.55, 56.33 MPa (complete osteotomy of facet joint) and 142.29, 103.02, 59.69 MPa (partial osteotomy of facet joint). Conclusions In percutaneous transforaminal lumbar interbody fusion, the fixation effect of BPS model was similar to that of LPS+TLFS model. BPS model could achieve the best spinal stability, and LPS+TLFS model was also a good fixation method. The stability of TLFS model alone was relatively poor, but it was still better than that of cage bone graft without internal fixation. In the absence of internal fixation, preservation of the articular process significantly increased stability of the spine.

14.
Acta Pharmaceutica Sinica ; (12): 2335-2345, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-886961

RESUMO

Oligonucleotides have attracted the widespread attention in disease diagnosis and gene therapy. At present, the nucleic acid drugs are at the forefront of biomedical and pharmaceutical research. The bioanalysis of therapeutic oligonucleotides has been slow, however, due to the requirements for pharmacokinetic/toxicokinetic and pharmacodynamic studies in pharmaceutical development. Conventionally, the hybridization-enzyme linked immunosorbent assay (hybridization-ELISA) is widely used in the bioanalysis of therapeutic oligonucleotides. Recentlly, many technologies such as real-time quantitative PCR (qPCR) and high performance liquid chromatography (HPLC)-based technologies have also showed a broad application prospects in the bioanalysis of therapeutic oligonucleotides. However, each technology has its own advantages and limitations. This review summarizes the currently used techniques in the bioanalysis of oligonucleotide therapeutics and reviews the challenges of regulated bioanalysis.

15.
IEEE Trans Neural Netw Learn Syst ; 31(7): 2638-2652, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31502991

RESUMO

Vector-valued neural learning has emerged as a promising direction in deep learning recently. Traditionally, training data for neural networks (NNs) are formulated as a vector of scalars; however, its performance may not be optimal since associations among adjacent scalars are not modeled. In this article, we propose a new vector neural architecture called the Arbitrary BIlinear Product NN (ABIPNN), which processes information as vectors in each neuron, and the feedforward projections are defined using arbitrary bilinear products. Such bilinear products can include circular convolution, 7-D vector product, skew circular convolution, reversed-time circular convolution, or other new products that are not seen in the previous work. As a proof-of-concept, we apply our proposed network to multispectral image denoising and singing voice separation. Experimental results show that ABIPNN obtains substantial improvements when compared to conventional NNs, suggesting that associations are learned during training.


Assuntos
Aprendizado Profundo , Redes Neurais de Computação , Neurônios , Máquina de Vetores de Suporte , Humanos , Neurônios/fisiologia
16.
Journal of Medical Biomechanics ; (6): E486-E492, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-802383

RESUMO

Objective To analyze the biomechanical characteristics of 3 different posterior internal fixation methods for treating thoracolumbar burst fracture by three-dimensional finite element (FE) method. Methods The FE fixation models of normal thoracolumbar, short-segment posterior fixation (SSPF), short-segment posterior fixation with intermediate screws at fractured level (SSPFI) and long-segment posterior fixation (LSPF) were established, respectively. The biomechanical characteristics of L1 centrum and the adjacent intervertebral disc under 6 kinds of motion states (spinal flexion, extension, lateral bending and axial rotation), in normal thoracolumbar model and 3 fixation models were compared by FE analysis. Results L1 centrum equivalent stress distributions in normal thoracolumbar model, SSPF model, SSPFI model, LSPF model were 31.63, 13.41, 110.35, 13.17 MPa, respectively. The maximum equivalent stress of adjacent intervertebral disc in normal thoracolumbar model was 3.84 MPa, which was located in L1-2 intervertebral disc; the maximum equivalent stress of adjacent intervertebral disc in 3 fixation models was 0.41, 0.36, 0.40 MPa, respectively, which was all located in T12-L1 intervertebral disc. Conclusions Fixation in short segment of the fractured vertebrae could lead to an increase of stress in the centrum. The stress of the adjacent intervertebral disc in 3 fixation models was smaller than that in normal spinal model.

17.
Chinese Journal of Neuromedicine ; (12): 1143-1146, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1034917

RESUMO

Objective To explore the changes of serum amyloid A (SAA) level and its clinical significance in patients with post-stroke depression (PSD). Methods One hundred and sixty-four patients with acute ischemic stroke, admitted to our hospital from January 2016 to June 2017 were assessed with Hamilton Depression Scale-17 (HAMD-17) to evaluate the depression degrees, and accordingly, they were divided into PSD group (n=57) and non-PSD group (n=107). Healthy volunteers who were examined in the corresponding period were selected as healthy control group (n=50). The SAA level was determined with ELISA in subjects of the 3 groups. Clinical data were collected; single factor analysis and multivariate Logistic regression analysis were performed to select the risk factors of PSD. Results The SAA level in PSD group ([18.85±5.25] mg/L) was significantly higher than that in the non-PSD group ([15.25±5.75] mg/L) and healthy control group ([7.65±4.50] mg/L, P<0.05); that in the non-PSD group was significantly higher than that in the healthy control group (P<0.05). Single factor analysis showed that differences in education level, introversion, economic status, living alone, marital status, National Institutes of Health Stroke Scale (NIHSS) scores≥9 at admission, complications, and proportion of key area infarction (frontal lobe and basal ganglia) had statistical significance between PSD group and non-PSD group (P<0.05). Multivariate Logistic regression analysis showed that introversion, poor economic status, living alone, NIHSS scores≥9, infarction of key areas, and elevation of SAA level (OR=1.545, P=0.035, 95% CI: 1.257-1.898) were independent risk factors for PSD (P<0.05). Conclusion SAA used as one of the detection biomarkers has great significance in early diagnosis, intervention and clinical prevention for PSD.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-698778

RESUMO

BACKGROUND: Preliminary studies have found that poly(lactic-co-glycolic acid) (PLGA) can improve the compressive strength and degradability of calcium phosphate cement. OBJECTIVE: To prepare a self-setting calcium phosphate cement which has better mechanical properties, biocompatibility and degradability on the basis of the previous findings. METHODS: Beta-tricalcium phosphate (β-TCP), pure calcium phosphate cement (CPC) and PLGA powder were mixed at different mixing ratios for preparation of PLGA/β-TCP/CPC. Setting time, compressive strength, elastic modulus and degradation properties of the composite bone cement were evaluated to screen the optimal level of β-TCP. MC3T3-E1 cells were cultured in CPC extract (control), PLGA/β-TCP/CPC extract (experimental), α-MEM containing 10% fetal bovine serum and 1% penicillin-streptomycin double antibody (negative control), and 6.4% phenol liquid (positive control). MTT method was used to detect cell proliferation at 1, 3, 5 days after culture, and lactate dehydrogenase activity in culture media was detected at 1 and 3 days after culture. MC3T3-E1 cells were seeded on the surface of PLGA/β-TCP/CPC and pure CPC respectively, and were then observed by scanning electron microscopy after 3 days. RESULTS AND CONCLUSION: Initial setting time and final setting time among of the composite bone cement were increased with the increasing of β-TCP content, but had no significant difference from those of the CPC (P > 0.05). The compressive strength and elastic modulus of the composite bone cement were higher than those of the CPC, and moreover, the composite bone cement with 20% β-TCP exhibited the highest compressive strength and higher elastic modulus as compared with the other groups. Therefore, PLGA/20% β-TCP/CPC was selected in the cell test. Moreover, the degradation properties of the composite bone cement were also better than those of the CPC. (3) With the growth of culture time, cell absorbance value and lactate dehydrogenase activity were gradually increased in the experimental group, and no difference existed between the experimental group and the negative control group. The cells in the experimental group also grew well. (4) MC3T3-E1 cells grew well and fully extended on the surface of PLGA/β-TCP/CPC, and cell pseudopodia on the material surface were tightly adhered to the material. To conclude, PLGA/20% β-TCP/CPC has better compressive strength, elastic modulus, degradation properties and cytocompatibility relative to the CPC, and moreover, the composite bone cement has no obvious cytotoxicity.

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