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1.
Proc Natl Acad Sci U S A ; 120(20): e2218739120, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37155879

RESUMO

Carbon-based nanomaterials (CNMs) have recently been found in humans raising a great concern over their adverse roles in the hosts. However, our knowledge of the in vivo behavior and fate of CNMs, especially their biological processes elicited by the gut microbiota, remains poor. Here, we uncovered the integration of CNMs (single-walled carbon nanotubes and graphene oxide) into the endogenous carbon flow through degradation and fermentation, mediated by the gut microbiota of mice using isotope tracing and gene sequencing. As a newly available carbon source for the gut microbiota, microbial fermentation leads to the incorporation of inorganic carbon from the CNMs into organic butyrate through the pyruvate pathway. Furthermore, the butyrate-producing bacteria are identified to show a preference for the CNMs as their favorable source, and excessive butyrate derived from microbial CNMs fermentation further impacts on the function (proliferation and differentiation) of intestinal stem cells in mouse and intestinal organoid models. Collectively, our results unlock the unknown fermentation processes of CNMs in the gut of hosts and underscore an urgent need for assessing the transformation of CNMs and their health risk via the gut-centric physiological and anatomical pathways.


Assuntos
Microbioma Gastrointestinal , Nanoestruturas , Nanotubos de Carbono , Humanos , Animais , Camundongos , Microbioma Gastrointestinal/fisiologia , Nanotubos de Carbono/efeitos adversos , Fermentação , Butiratos/metabolismo
2.
J Med Virol ; 96(3): e29546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38516804

RESUMO

Tapasin, a crucial molecular chaperone involved viral antigen processing and presentation, plays an important role in antivirus immunity. However, its impact on T cell differentiation in the context of virus clearance remains unclear. In this study, we employed induced pluripotent stem cells to differentiate into hepatocyte-like cell, which were subsequently inserted to the inverted colloidal crystal scaffolds, thus establishing a hepatocyte organoid (HO). By inoculating hepatitis B virus (HBV) particles in the system, we successfully engineered a robust in vitro HBV infection model for at least 3 weeks. Furthermore, we aimed to explore the effects of lentivirus-mediated short hairpin RNA (shRNA) targeting human Tapasin on the differentiation and antiviral function of CD8+ T cells. Specifically, we transfected dendritic cells (DCs) with Tapasin-shRNA and cocultured with T cells. The results demonstrated that Tapasin-shRNA transfected DCs effectively suppressed T cell proliferation and impeded HBV-specific cytotoxic T lymphocyte responses. Our investigation also revealed the role of mTOR pathway activation in reducing autophagy activity within CD8+ T cells. Expressions of autophagy-related proteins, beclin-1, LC3II/LC3I were decreased and PI3K/AKT/mTOR activity was increased in Tapasin-shRNA group. Collectively, our findings elucidate that shRNA targeting the Tapasin gene within DCs inhibits T cell differentiation by reducing autophagy activity to hamper viral clearance in the HBV-infected HO.


Assuntos
Células Dendríticas , Hepatite B , Proteínas de Membrana Transportadoras , Humanos , Autofagia/genética , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas/metabolismo , Regulação para Baixo , Hepatite B/metabolismo , Antígenos do Núcleo do Vírus da Hepatite B/genética , Vírus da Hepatite B , Hepatócitos/metabolismo , Células-Tronco Pluripotentes Induzidas , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , RNA Interferente Pequeno/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Organoides/metabolismo , Organoides/virologia
3.
J Med Virol ; 95(4): e28746, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37185848

RESUMO

Hepatitis B virus (HBV) specific T cell immune response plays a vital role in viral clearance. Dendritic cell derived exosomes (Dexs) can activate T cell immunity effectively. Tapasin (TPN) is involved in antigen processing and specific immune recognition. In the present study, we elucidated that Dexs loading TPN (TPN-Dexs) could enhance CD8+ T cell immune response and inhibit virus replication in HBV transgenic mice. T cell immune response and the ability of inhibiting HBV replication were measured in HBV transgenic mice immunized with TPN-Dexs. Meanwhile, CD8+ T cell autophagy and specific T cell immune responses were measured in vitro and vivo, and the mechanisms probably involved in were explored. Purified TPN-Dexs could be taken up into the cytoplasm of DCs and upregulate CD8+ T cell autophagy to enhance specific T cell immune response. In addition, TPN-Dexs could increase the expression of AKT and decrease the expression of mTOR in CD8+ T cells. Further research confirmed that TPN-Dexs could inhibit virus replication and decrease the expression of HBsAg in the liver of HBV transgenic mice. Nevertheless, those also could elicit mice hepatocytes damage. In conclusion, TPN-Dexs could enhance specific CD8+ T cell immune responses via the AKT/mTOR pathway to regulate the autophagy and exert the antiviral effect in HBV transgenic mice.


Assuntos
Exossomos , Vírus da Hepatite B , Camundongos , Animais , Linfócitos T CD8-Positivos , Proteínas Proto-Oncogênicas c-akt , Camundongos Transgênicos , Serina-Treonina Quinases TOR , Apresentação de Antígeno , Autofagia , Camundongos Endogâmicos C57BL
4.
Aging Male ; 26(1): 2235005, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37452735

RESUMO

BACKGROUND: China is one of the countries with the fastest growing prevalence of diabetes mellitus (DM) in the world. This study intended to investigate the association of single nucleotide polymorphisms (SNPs) of FHL5 and LPA with DM risk in the Chinese population. METHODS: This case-control study involved 1,420 Chinese individuals (710 DM patients and 710 controls). Four candidate loci (rs2252816/rs9373985 in FHL5 and rs3124784/rs7765781 in LPA) were successfully screened. The association of SNPs with DM risk was assessed by logistic regression analysis. Differences in clinical characteristics among subjects with different genotypes were analyzed by one-way analysis of variance. RESULTS: Overall analysis indicated that rs3124784 was associated with an increased risk of DM. Stratification analysis showed that rs3124784 significantly increased DM risk in different subgroups (male, non-smoking, non-drinking, and BMI > 24), while rs7765781 increased DM risk only in participants with BMI ≤ 24. Rs2252816 was associated with the course of DM. We also found that rs2252816 GG genotype and rs9373985 GG genotype were linked to the increased cystatin c in DM patients. CONCLUSION: The genetic polymorphisms of LPA may be associated with DM risk in the Chinese population, which will provide useful information for the prevention and diagnosis of DM.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Humanos , Masculino , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Genótipo , China/epidemiologia , Fatores de Transcrição/genética , Proteínas com Domínio LIM/genética
5.
J Biopharm Stat ; : 1-19, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37621147

RESUMO

Inverse probability weighting (IPW) is frequently used to reduce or minimize the observed confounding in observational studies. IPW creates a pseudo-sample by weighting each individual by the inverse of the conditional probability of receiving the treatment level that he/she has actually received. In the pseudo-sample there is no variation among the multiple individuals generated by weighting the same individual in the original sample. This would reduce the variability of the data and therefore bias the variance estimate in the target population. Conventional variance estimation methods for IPW estimators generally ignore this underestimation and tend to produce biased estimates of variance. We here propose a more reasonable method that incorporates this source of variability by using parametric bootstrapping based on intra-stratum variability estimates. This approach firstly uses propensity score stratification and intra-stratum standard deviation to approximate the variability among multiple individuals generated based on a single individual whose propensity score falls within the corresponding stratum. The parametric bootstrapping is then used to incorporate the target variability by re-generating outcomes after adding a random error term to the original data. The performance of the proposed method is compared with three existing methods including the naïve model-based variance estimator, the nonparametric bootstrap variance estimator, and the robust variance estimator in the simulation section. An example of patients with sarcopenia is used to illustrate the implementation of the proposed approach. According to the results, the proposed approach has desirable statistical properties and can be easily implemented using the provided R code.

6.
Eur Radiol ; 32(9): 6080-6089, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35364716

RESUMO

OBJECTIVES: We aimed to investigate the associations between carotid vulnerable plaque features coexisting with cerebral small vessel diseases (CSVDs) and acute ischemic stroke (AIS) and, furthermore, to determine whether coexisting diseases had a stronger association with AIS than a single disease. METHODS: Patients with cerebrovascular symptoms and carotid plaque were recruited from the cross-sectional, multicenter CARE-II study. The population was divided into two groups (AIS and transient ischemic stroke (TIA)). MRI features of carotid plaques (including luminal stenosis and plaque vulnerabilities) and CSVDs (such as white matter hyperintensities (WMHs) and lacunes) were evaluated. Coexisting diseases were defined as the presence of at least one carotid plaque features and one or more CSVDs feature. Multivariate logistic regression was performed to examine the associations between coexisting diseases and AIS. RESULTS: Of the recruited 634 patients (mean age: 59.1 ± 11.3 years; 429 males), 312 (49.2%) patients had AIS. These subjects had a higher prevalence of carotid vulnerable plaques, lacunes, and moderate-to-severe WMHs (a total Fazekas score of 3-6) than those with TIA (42.6% vs. 29.5%, 59.6% vs. 26.4%, 69.9% vs. 60.6%, respectively, all p < 0.05). Multivariate analysis revealed that carotid plaque features coexisting with lacunes or moderate-to-severe WMHs had a stronger association with AIS compared to carotid lesions alone (all p < 0.05) (i.e., vulnerable plaque coexisting with lacunes vs. vulnerable plaque alone, adjusted odds ratio: 3.67 vs. 1.62). CONCLUSIONS: Carotid vulnerable plaque features coexisting with CSVDs, particularly lacunes, had a stronger association with AIS compared to carotid lesions alone in a large, symptomatic, cohort. TRIAL REGISTRATION: Clinical trial registration URL: http://www. CLINICALTRIALS: gov , unique identifier: NCT02017756 KEY POINTS: • Carotid vulnerable plaque features coexisting with cerebral small vessel diseases, such as lacunes, had a stronger association with acute ischemic stroke compared to single diseases in symptomatic patients. • A comprehensive assessment of coexisting cerebrovascular diseases may help stratify the risk of acute ischemic stroke.


Assuntos
Aterosclerose , Estenose das Carótidas , Doenças de Pequenos Vasos Cerebrais , Ataque Isquêmico Transitório , AVC Isquêmico , Placa Aterosclerótica , Acidente Vascular Cerebral , Idoso , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/epidemiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , China/epidemiologia , Estudos Transversais , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/epidemiologia , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
7.
Eur Arch Otorhinolaryngol ; 279(2): 1035-1042, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34110454

RESUMO

PURPOSE: The psychological status of nasopharyngeal carcinoma (NPC) patients cannot be ignored. Few studies have studied the dynamic changes and influencing factors of psychological status in NPC patients during radiotherapy. The purpose of this study was to investigate the changing trends and risk factors of anxiety and depression in NPC patients during radiotherapy. METHODS: Demographic and clinical data of 232 newly treated NPC patients were collected. Before radiotherapy, the fourth week, and the end of radiotherapy were observational timepoints. Anxiety and depression states were evaluated by the hospital anxiety and depression scale. RESULTS: Scores of anxiety before radiotherapy, in the fourth week and at the end of radiotherapy were 6.32 ± 3.19, 7.87 ± 3.49, and 9.08 ± 3.69, respectively (P < 0.001). Incidence rates of anxiety were 34.0%, 55.1%, and 64.0% (P < 0.001). Depression scores were 5.31 ± 3.19, 7.07 ± 3.63, and 8.32 ± 3.89 (P < 0.001). Incidence rates of depression were 25.0%, 43.9%, and 56.0% (P < 0.001). Gender, age, education level, smoking, and treatment-related toxicity scores (P < 0.05) were independent risk factors for anxiety in patients with NPC during radiotherapy, while age, education level, and treatment-related toxicity scores (P < 0.05) were independent risk factors for depression in these patients. CONCLUSION: The incidence and degree of anxiety and depression in NPC patients increased during radiotherapy. Age, education level, and treatment-related side effects influenced anxiety and depression. More psychological nursing should be given to the NPC patients who are more likely to suffer from psychological distress.


Assuntos
Neoplasias Nasofaríngeas , Ansiedade/epidemiologia , Ansiedade/etiologia , Transtornos de Ansiedade , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia/efeitos adversos
8.
Phytochem Anal ; 33(4): 635-643, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35229907

RESUMO

INTRODUCTION: The comprehensive component characterisation of Chinese herbal medicine is the premise of effectively driving the discovery of pharmacodynamic substances or new drugs in recent years. OBJECTIVE: To use the high-throughput liquid chromatography-mass spectrometry (LC-MS) approach to systematically characterise phytochemical compounds from four hawthorn leaf extracts, along with evaluating their classification. METHODS: In the present study, the compounds from 50% ethanol extract, macro porous resin extract, ethyl acetate extract and standard decoction of hawthorn leaves were completely analysed by ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). RESULTS: Eight-nine compounds were putatively identified by comparison with secondary MS data and available references. Of these compounds identified, 56 compounds were found for the first time in hawthorn leaves, which was somewhat inconsistent with the findings of other studies. It could be inferred that falconoid, organic acids and nitrogenous compounds were the most abundant in 50% ethanol extract and standard decoction extract, which were considered as better choices for extracting hawthorn leaves. CONCLUSIONS: This work developed a simple, accurate and rapid method for the compound identification of hawthorn leaves, which laid the basis for further discovering pharmacodynamic material basis or new drugs from hawthorn leaves.


Assuntos
Crataegus , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Crataegus/química , Etanol , Extratos Vegetais/química , Espectrometria de Massas em Tandem
9.
Angew Chem Int Ed Engl ; 61(44): e202205301, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-35866885

RESUMO

The electrocatalytic CO2 reduction reaction (ECO2 RR) is one promising method for storing intermittent clean energy in chemical bonds and producing fuels. Among various kinds of catalysts for ECO2 RR, molecular metal complexes with well-defined structures are convenient for studies of their rational design, structure-reactivity relationships, and mechanisms. In this Review, we summarize the molecular engineering of several N-based metal complexes including Re/Mn bipyridine compounds and metal macrocycles, concluding with general modification strategies to devise novel molecular catalysts with high intrinsic activity. Through physical adsorption, covalent linking, and formation of a periodic backbone, these active molecules can be heterogenized into immobilized catalysts with more practical prospects. Finally, significant challenges and opportunities based on molecular catalysts are discussed.

10.
Angew Chem Int Ed Engl ; 61(27): e202200751, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35441773

RESUMO

A triblock amphiphilic polymer derived from the copolymerization of CO2 and epoxides containing a bipyridine rhenium complex in its backbone is shown to effectively catalyze the visible-light-driven reduction of CO2 to CO. This polymer provides uniformly spherical micelles in aqueous solution, where the metal catalyst is sequestered in the hydrophobic portion of the nanostructured micelle. CO2 to CO reduction occurs in an efficient visible-light-driven process in aqueous media with turnover numbers up to 110 (>99 % selectivity) in the absence of a photosensitizer, which is a 37-fold enhancement over the corresponding molecular rhenium catalyst in organic solvent. Notably, the amphiphilic polycarbonate micelle rhenium catalyst suppresses H2 generation, presumably by preventing deactivation of the active catalytic center by water.

11.
Support Care Cancer ; 29(10): 5967-5972, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33765206

RESUMO

PURPOSE: To explore whether anxiety and depression are prognostic indexes for overall survival in patients with nasopharyngeal carcinoma (NPC) who underwent intensity-modulated radiotherapy (IMRT). METHODS: Clinical data were collected for NPC patients who underwent IMRT. Anxiety and depression were investigated before radiotherapy by using the Hospital Anxiety and Depression Scale (HADS). The survival rate was calculated by the Kaplan-Meier method, and survival curves were compared among patients with different levels of anxiety and depression. The Cox risk regression model was used to screen the factors affecting survival. RESULTS: A total of 390 initially treated NPC patients were included in the study. Among them, 166 patients suffered from anxiety, and 95 patients suffered from depression before radiotherapy. The 5-year overall survival rates for patients with and without anxiety before radiotherapy were 71.6% and 81.8% (χ2 = 5.31, P = 0.021), respectively. The 5-year overall survival rates for patients with and without depression before radiotherapy were 74.3% and 78.1% (χ2 = 0.05, P = 0.82), respectively. Cox regression analysis indicated clinical stages (HR = 3.982, 95% CI: 2.365~6.705), anxiety (HR = 1.832, 95% CI: 1.140~2.944), and gender (HR = 0.555, 95% CI: 0.313~0.984) as independent prognostic factors. CONCLUSION: Anxiety before radiotherapy is associated with poor prognosis in NPC patients.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
12.
Ecotoxicol Environ Saf ; 225: 112715, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34500382

RESUMO

As a natural heme protein catalyzing the oxidation of sulfides to sulfoxides without sulfone formation, chloroperoxidase (CPO) is well suited for the degradation of sulfur mustard (HD), a persistent chemical warfare agent that has been widely disposed since World War II and continuously leaks into aquatic environments. Herein, we report the first systematic investigation of CPO-catalyzed degradation of HD and the potential application of CPO in destroying chemical weapons under mild conditions. The related Michaelis-Menten parameters (Km=0.17 mM, Vmax=0.06 mM s-1 (R2 =0.935), and kcat= 2717 s-1) indicated nearly a prominent enzymatic efficiency. Under optimal conditions, 80% of HD was transformed to bis(2-chloroethyl) sulfoxide as identified by mass spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. Other metabolites were also generated during the decontamination process. A plausible oxidation mechanism was proposed based on the degradation products, NMR titration experiments, and molecular dynamics simulations. CPO also promoted the degradation of other chemical weapon agents, namely, Lewisite (L) and venomous agent X (VX), thereby exhibiting a broad substrate scope. The high potential of the developed system for the decontamination of aquatic environments was demonstrated by the successful hatching of zebrafish embryos after HD degradation and the survival of zebrafish (Danio rerio, AB strain) larvae after the degradation of Agent Yellow (L+HD).


Assuntos
Cloreto Peroxidase , Gás de Mostarda , Animais , Catálise , Gás de Mostarda/toxicidade , Estresse Oxidativo , Peixe-Zebra/metabolismo
13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(5): 743-748, 2021 Oct.
Artigo em Zh | MEDLINE | ID: mdl-34728035

RESUMO

Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(χ2=33.520,P<0.001).Conclusion After HIV-positive mothers in Lingshan County of Guangxi received ART for PMTCT,the incidence of growth stunting in 18-month-old children increased.


Assuntos
Infecções por HIV , Complicações Infecciosas na Gravidez , Estudos de Casos e Controles , China/epidemiologia , Feminino , Crescimento e Desenvolvimento , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mães , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Retrospectivos
14.
Cytokine ; 119: 113-118, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30903865

RESUMO

Recent studies have provided overwhelming evidence of the involvement of microglia-related molecular networks in the pathogenesis of Alzheimer's diseases (AD). The potential involvement of pro-inflammatory cytokines interleukin (IL)-18, IL-23 and IL-17 on amyloid (Aß) clearance is still unclear. In this study, we addressed that there might be a net relationship among IL-18, IL-23, and IL-17 and they can affect Aß clearance in cultured macrophage/microglia cells. In human macrophage cell line THP-1, Aß42 incubation could increase the expression of IL-18, IL-23 and IL-17 in a concentration dependent manner. THP-1 cell could clear Aß42 in the culture medium time-dependently, but its capacity of Aß clearance was impaired by IL-18, IL-23 or IL-17 treatment. Similarly, the capacity of the microglia cell line BV2 to clear Aß42 was impaired by IL-18, IL-23 or IL-17 treatment. In co-cultures of BV2 with APP/PS1 neuron, Aß was efficiently cleared by BV2 cell, but Aß clearance was impaired by IL-18, IL-23 or IL-17 treatment. The effects of IL-18, IL-23 and IL-17 could be blocked by their corresponding neutralizing antibodies. In addition, the inhibitory effects of IL-18 were blocked by IL-23 or IL-17 neutralizing antibodies while the inhibitory effects of IL-23 were blocked by IL-17 neutralizing antibodies. Our study provides evidences showing that amyloid induced IL-18/IL-23/IL-17 axis could impair macrophage and microglia-mediated Aß clearance. Thus, IL-18/IL-23/IL-17 axis might be a therapeutic target in AD.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Interleucina-17/metabolismo , Interleucina-18/metabolismo , Subunidade p19 da Interleucina-23/metabolismo , Células THP-1/metabolismo , Doença de Alzheimer/metabolismo , Animais , Encéfalo/metabolismo , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Neurônios/metabolismo
15.
Intervirology ; 61(6): 281-291, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31018203

RESUMO

OBJECTIVES: The epidemiological evidence is inconsistent about whether HIV-positive injection drug users (IDUs) are at higher risk of developing antiretroviral resistance than any other HIV-positive populations. This study aims to investigate and compare transmitted drug resistance (TDR) between IDUs and non-IDUs in Lingshan County, an HIV-hit region in Guangxi, China, where IDU and heterosexual transmission were the two dominant transmission routes and roughly equally contributed to the local HIV transmission. METHODS: A cross-sectional study was conducted among newly diagnosed and antiretroviral-treatment (ART)-naïve HIV-1 patients from Lingshan County. The pol gene of HIV-1 from the individuals was sequenced followed by genotyping and TDR analysis. RESULTS: Two dominant transmission routes, heterosexual contact and IDU, accounted for 49.2 and 45.9% of 183 HIV-1 infection cases, respectively. Three genotypes, including CRF08_BC (70.6%), CRF01_AE (24.4%), and CRF07_BC (5.0%), and three unique recombinant forms (1.6%), were identified. There was a significant difference in genotype distribution among the different transmission routes (F = 21.814, p < 0.001). The overall TDR prevalence was 5.5%. There were no significant differences in TDR prevalence among the different transmission routes (F = 1.420, p = 0.439). CONCLUSIONS: Injection drug use has little impact on TDR prevalence compared with other routes of transmission.


Assuntos
Farmacorresistência Viral , Usuários de Drogas , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , China/epidemiologia , Estudos Transversais , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Prevalência , Recombinação Genética , Carga Viral , Adulto Jovem
16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 42(4): 413-418, 2017 Apr 28.
Artigo em Zh | MEDLINE | ID: mdl-28490699

RESUMO

OBJECTIVE: To explore the effectof tumor volume on pulmonary dose-volume parameters by intensity-modulated radiation therapy (IMRT) in non-small cell lung cancer (NSCLC), and to provide a basis for pulmonary dose parameters in IMRT treatment.
 Methods: A total of 204 patients with NSCLC received IMRT were retrospectively analyzed from June, 2009 to October, 2013. The prescribed dose of planning target volume (PTV) for primary tumor was 60-66Gy (2.00-2.25 Gy, 27-33 times in all). The fractional volume percent of the lung received a dose >5 or 20 Gy (V5, V20), and absolute volume of lung received a dose <5 Gy (AVS5).The mean lung dose (MLD) in normal tissues were analyzed. Regression model curve was used to analyze them along with the change of primary tumor volume.
 Results: With the increase in lung tumor volume, the V5, V20 and MLD presented quadratic equation curve, and AVS5 presented logarithmic equation. When the tumor volume, less than a certain value (294.6, 283.2, 304.9 cm3, respectively), the V5, V20 and MLD increased with tumor size and presented an increased quadratic curve; when the tumor volume was higher than a certain value (294.6, 283.2, 304.9 cm3 respectively), the V5, V20 and MLD was declined. The AVS5 was declined in a logarithmic curve along with the increase of tumor volume.
 Conclusion: With the increase in lung tumor volume, the change in rule of V5, V20, MLD and AVS5 is not completely equivalent. When the tumor volume exceeds a certain boundary value (about 300 cubic centimeter), the corresponding tumor diameter is about 7-8 cm. In addition to the focus on pulmonary V5, V20 and MLD, we should also pay more attention to AVS5 restrictions in establishment of IMRT in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Carga Tumoral/efeitos da radiação , Humanos , Neoplasias Pulmonares , Dosagem Radioterapêutica/normas , Estudos Retrospectivos
17.
Zhong Yao Cai ; 38(6): 1183-5, 2015 Jun.
Artigo em Zh | MEDLINE | ID: mdl-26762058

RESUMO

OBJECTIVE: To establish the HPLC fingerprint of Clerodendrum lindleyi in order to provide the basis for its quality standard. METHODS: The chromatographic fingerprint was obtained with Angilent Zorbax C18 (250 mm x 4.6 mm, 5 µm) column and gradiently eluted with acetonitrile-0.1% phosphoric acid solution. The column temperature was maintained at 35 degrees C. The flow rate was 1.0 mL/min and the detection wavelength was 327 nm. RESULTS: HPLC fingerprint of Clerodendrum lindleyi was established and 21 common peaks from 11 batches of samples were found. CONCLUSION: The method has good precision, stability and repeatability, which can provide reliable basis for quality evaluation of Clerodendrum lindleyi.


Assuntos
Cromatografia Líquida de Alta Pressão , Clerodendrum/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/normas , Controle de Qualidade
18.
Dement Geriatr Cogn Disord ; 38(5-6): 321-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25138786

RESUMO

AIMS: To evaluate the serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with Alzheimer's disease (AD), and explore correlations between the three cytokines and relevant parameters. METHODS: Serum concentrations of IL-18, IL-23 and IL-17 were measured by ELISA for 53 AD patients and 53 sex- and age-matched healthy controls in a community of elderly individuals in a Shanghai suburb. RESULTS: Serum concentrations of IL-18, IL-23 and IL-17 were significantly higher in AD patients than controls. The serum level of IL-23 was observed to be significantly higher (p = 0.049) in female AD patients than male AD patients. In addition, a significantly inverse correlation was found between IL-18 and MMSE score (rs = -0.356, p = 0.011) for all AD patients. CONCLUSION: Elevated IL-18, IL-23 and IL-17 levels are observed in AD patients and differences may exist between males and females. Besides, IL-18 may correlate with the severity of AD.


Assuntos
Doença de Alzheimer/sangue , Interleucina-17/sangue , Interleucina-18/sangue , Interleucina-23/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Povo Asiático , China , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Fatores Sexuais
19.
Pain Med ; 15(9): 1464-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24506258

RESUMO

OBJECTIVE: To investigate the clinical efficacy of X-ray imaging combined with skin stimulation potential-guided percutaneous radiofrequency thermocoagulation of the Gasserian ganglion for treatment of primary trigeminal neuralgia. DESIGN: This is a prospective, randomized study. Sixty patients with primary trigeminal neuralgia were randomly assigned to a study group or control group. In the study group, the patients underwent X-ray imaging combined with skin stimulation potential-guided percutaneous radiofrequency thermocoagulation of the Gasserian ganglion. The patients in the control group underwent C-arm X-ray-guided puncture through the foramen ovale, and then the puncture needle was microscopically adjusted according to the intensity of the masticatory muscle response and the patients' reactions. Puncture success, postoperative adverse reactions, and short- and middle-term analgesic efficacies were statistically compared between the two surgical approaches. RESULTS: The incidence of postoperative side effects was significantly reduced, and immediate and mid-term analgesic efficacy was better in patients in the study group comparing with those in the control group (P < 0.01). CONCLUSION: Using skin stimulation potential-guided puncture may enable more accurate microscopic adjustment of the targets localization damaged by radiofrequency and significantly enhanced clinical efficacy in this study.


Assuntos
Eletrocoagulação/métodos , Eletrodiagnóstico/métodos , Terapia por Radiofrequência , Radiografia Intervencionista , Pele/inervação , Gânglio Trigeminal , Nervo Trigêmeo/fisiopatologia , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Eletrocoagulação/efeitos adversos , Eletrocoagulação/instrumentação , Eletrodiagnóstico/instrumentação , Feminino , Humanos , Masculino , Músculo Masseter/fisiologia , Pessoa de Meia-Idade , Entorpecentes/uso terapêutico , Estudos Prospectivos , Osso Esfenoide , Tramadol/uso terapêutico , Resultado do Tratamento , Gânglio Trigeminal/fisiopatologia , Neuralgia do Trigêmeo/tratamento farmacológico
20.
Med Educ Online ; 29(1): 2325182, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38465652

RESUMO

Phenomenon: The increase in clinical and teaching workload has brought enormous pressure to clinical teachers. Clinical teachers play an extremely important role in the quality of higher medical education and the cultivation of medical talents. However, few studies have examined the attitudes and practices of clinical teachers regarding the role of teachers in China. This study aimed to investigate clinical teachers' perceptions about their roles and current practices at affiliated hospitals of medical universities in China. Approach: Responses from 312 Chinese clinical teachers were included in the analyses. The data were collected using the questionnaires of perception and practice regarding the role of teachers which consisted of 12 items rated on a 5-point Likert scale, ranging from 1 (strongly disagree) to 5 (strongly agree), and scored by calculating the mean. The data were analyzed using the Statistical Package for Social Sciences, version 22.0 (IBM SPSS Corp). Findings: The mean score of perception of clinical teachers regarding the role of teachers was 4.51 (SD = 0.72), and the mean score of practice was 3.69 (SD = 1.17). Multivariable binary logistic regression model showed that undertaking very few/few clinical teaching workload, 'thinking it is my obligation to carry out teaching work seriously' and 'thinking it is my duty to train medical talents' were not only significant determinants of good perception but also good practice. Additionally, 'thinking hospital attached great importance to clinical teaching' was the significant determinant of good perception. Insights: Chinese clinical teachers demonstrate less positive perception and practice regarding the roles of teacher than clinical teachers in developed countries. Affiliated hospitals of medical universities should hold training sessions regularly and take targeted intervention measures to enhance clinical teachers' perception and practice regarding the roles of teacher.


Assuntos
Educação Médica , Docentes , Humanos , Universidades , Inquéritos e Questionários , Percepção
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