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2.
Iran J Allergy Asthma Immunol ; 22(3): 290-298, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37524665

RESUMO

Asthma is a common chronic airway inflammation that produces a healthcare burden on the economy. We aim to obtain a better understanding of the clinical status and disease burden of patients with asthma in China. A retrospective study was carried out based on the computerized medical records in the Jinan Health Medical Big Data Platform between 2011 and 2019 (available data from 38 hospitals). The asthma severity of each patient was assessed retrospectively and categorized as mild, moderate, or severe according to Global Initiative for Asthma 2020 (GINA 2020). The results revealed that the majority (75.0%) of patients suffered from mild asthma. Patients treated with inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) at emergency department visits had lower frequencies of exacerbations compared with non-ICS/LABA-treated patients. The incidence rates for 1, 2, 3, and 4 exacerbation of the patients treated with ICS/LABA are lower than those treated without ICS/LABA (14.49 vs. 15.01%, 11.94% vs. 19.12%, 6.51% vs.12.92% and 4.10% vs. 9.35%). The difference got a statistical significance Chronic obstructive pulmonary disease (COPD) and gastroesophageal reflux disease (GERD), two comorbidities related to asthma, were risk factors for asthma exacerbation. Finally, patients who suffered from exacerbations produced a heavier economic burden compared to the patients who never suffered exacerbations (mean costs are ï¿¥3,339.67 vs. ï¿¥968.45 separately).  These results provide a reference for clinicians and patients to obtain a better treatment and therapy strategy management for people living with asthma.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Retrospectivos , Estresse Financeiro , Administração por Inalação , Asma/tratamento farmacológico , Asma/epidemiologia , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2 , Quimioterapia Combinada
3.
J Am Chem Soc ; 145(24): 13469-13475, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37285591

RESUMO

Immobilization of fragile enzymes in crystalline porous materials offers new opportunities to expand the applications of biocatalysts. However, limited by the pore size and/or harsh synthesis conditions of the porous hosts, enzymes often suffer from dimension limitation or denaturation during the immobilization process. Taking advantage of the dynamic covalent chemistry feature of covalent organic frameworks (COFs), herein, we report a preprotection strategy to encapsulate enzymes in COFs during the self-repairing and crystallization process. Enzymes were first loaded in the low-crystalline polymer networks with mesopores formed at the initial growth stage, which could offer effective protection for enzymes from the harsh reaction conditions, and subsequently the encapsulation proceeded during the self-repairing and crystallization of the disordered polymer into the crystalline framework. Impressively, the biological activity of the enzymes can be well-maintained after encapsulation, and the obtained enzyme@COFs also show superior stability. Furthermore, the preprotection strategy circumvents the size limitation for enzymes, and its versatility was verified by enzymes with different sizes and surface charges, as well as a two-enzyme cascade system. This study offers a universal design idea to encapsulate enzymes in robust porous supports and holds promise for developing high-performance immobilized biocatalysts.


Assuntos
Estruturas Metalorgânicas , Cristalização , Enzimas Imobilizadas , Polímeros , Porosidade
4.
Angew Chem Int Ed Engl ; 62(33): e202306621, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37310867

RESUMO

The design of porous microcapsules with selective mass transfer and mechanical robustness for enzyme encapsulation is highly desired for biocatalysis, yet the construction remains challenging. Herein, we report the facile fabrication of porous microcapsules by assembling covalent organic framework (COF) spheres at the interfaces of emulsion droplets followed by interparticle crosslinking. The COF microcapsules could offer an enclosed aqueous environment for enzymes, with size-selective porous shells that allow for the fast diffusion of substrates and products while excluding larger molecules such as protease. Crosslinking of COF spheres not only enhances the structural stability of capsules but also imparts enrichment effects. The enzymes encased in the COF microcapsules show enhanced activity and durability in organic media as verified in both batch reaction and continuous-flow reaction. The COF microcapsules offer a promising platform for the encapsulation of biomacromolecules.


Assuntos
Estruturas Metalorgânicas , Cápsulas , Porosidade , Catálise , Biocatálise
5.
Angew Chem Int Ed Engl ; 62(17): e202300373, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-36857082

RESUMO

Pore environment and aggregated structure play a vital role in determining the properties of porous materials, especially regarding the mass transfer. Reticular chemistry imparts covalent organic frameworks (COFs) with well-aligned micro/mesopores, yet constructing hierarchical architectures remains a great challenge. Herein, we reported a COF-to-COF transformation methodology to prepare microtubular COFs. In this process, the C3 -symmetric guanidine units decomposed into C2 -symmetric hydrazine units, leading to the crystal transformation of COFs. Moreover, the aggregated structure and conversion degree varied with the reaction time, where the hollow tubular aggregates composed of mixed COF crystals could be obtained. Such hierarchical architecture leads to enhanced mass transfer properties, as proved by the adsorption measurement and chemical catalytic reactions. This self-template strategy was successfully applied to another four COFs with different building units.

6.
Int J Pharm ; 625: 122081, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-35934166

RESUMO

Corneal neovascularization (CNV) is a sequela of anterior segment inflammation, which could lead to vision impairment and even blindness. In the present study, the dual delivery of anti-inflammatory agent (i.e., diclofenac; DIC) and anti-VEGF antibody (i.e., Avastin®; Ava) by the thermosensitive hydrogel (Poly(dl-lactide)-poly(ethylene glycol)-poly(dl-lactide); PDLLA-PEG-PDLLA) is expected to effectively inhibit CNV via their synergistic effects. The optimal DIC micelles were formulated and then mixed with Ava and PDLLA-PEG-PDLLA aqueous solution to generate various DIC@Ava-loaded hydrogels. The co-encapsulation of DIC micelles and Ava did not influence the gelling behavior of the system, and the resulting DIC@Ava-loaded hydrogel provided sustained drug release of both DIC and Ava without compromising their pharmacological activity over 19 days. As indicated by in vitro cytotoxicity and in vivo ocular biocompatibility test, the proposed PDLLA-PEG-PDLLA hydrogel caused minimal cytotoxicity against all tested cell lines at a polymeric concentration ranging from 0.05 mg/mL to 0.8 mg/mL and demonstrated good ocular biocompatibility after a single subconjunctival injection. Using the rabbit CNV model, we documented the superior anti-angiogenic effects of the DIC@Ava-loaded hydrogel over Ava alone medication (treatment with Ava solution and Ava-loaded hydrogel) due to synergistic effects of anti-VEGF and anti-inflammatory action. Overall, the proposed DIC@Ava-loaded hydrogel might be a powerful strategy to reduce CNV.


Assuntos
Neovascularização da Córnea , Hidrogéis , Inibidores da Angiogênese/farmacologia , Animais , Bevacizumab , Materiais Biocompatíveis/uso terapêutico , Neovascularização da Córnea/tratamento farmacológico , Neovascularização da Córnea/metabolismo , Diclofenaco/farmacologia , Micelas , Polietilenoglicóis , Coelhos
7.
Angew Chem Int Ed Engl ; 61(21): e202201378, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35267241

RESUMO

Controllable regulations on the enzyme conformation to optimize catalytic performance are highly desired for the immobilized biocatalysts yet remain challenging. Covalent organic frameworks (COFs) possess confined channels with finely tunable pore environment, offering a promising platform for enzyme encapsulation. Herein, we covalently immobilized the cytochrome c (Cyt c) in the size-matched channels of COFs with different contents of anchoring site, and significant enhancement of the stability and activity (≈600 % relative activity compared with free enzyme) can be realized by optimizing the covalent interactions. Structural analyses on the immobilized Cyt c suggest that covalent bonding could induce conformational perturbation resulting in more accessible active sites. The effectiveness of the covalent interaction modulation together with the tailorable confined channels of COFs offers promise to develop high-performance biocatalysts.


Assuntos
Estruturas Metalorgânicas , Catálise , Domínio Catalítico , Enzimas Imobilizadas/química , Estruturas Metalorgânicas/química
8.
Mol Cancer ; 21(1): 4, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980131

RESUMO

BACKGROUND: Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown. METHODS: Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values. RESULTS: Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy. CONCLUSION: On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03668496.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Ácidos Nucleicos Livres , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Terapia Combinada , Biologia Computacional/métodos , DNA de Neoplasias , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Mutação , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento
9.
BMC Anesthesiol ; 22(1): 16, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996374

RESUMO

BACKGROUND: Sepsis is a highly heterogeneous syndrome with stratified severity levels and immune states. Even in patients with similar clinical appearances, the underlying signal transduction pathways are significantly different. To identify the heterogeneities of sepsis from multiple angles, we aimed to establish a combined risk model including the molecular risk score for rapid mortality prediction, pathway risk score for the identification of biological pathway variations, and immunity risk score for guidance with immune-modulation therapy. METHODS: We systematically searched and screened the mRNA expression profiles of patients with sepsis in the Gene Expression Omnibus public database. The screened datasets were divided into a training cohort and a validation cohort. In the training cohort, authentic prognostic predictor characteristics (differentially expressed mRNAs, pathway activity variations and immune cells) were screened for model construction through bioinformatics analysis and univariate Cox regression, and a P value less than 0.05 of univariate Cox regression on 28-day mortality was set as the cut-off value. The combined risk model was finally established by the decision tree algorithm. In the validation cohort, the model performance was assessed and validated by C statistics and the area under the receiver operating characteristic curve (AUC). Additionally, the current models were further compared in clinical value with traditional indicators, including procalcitonin (PCT) and interleukin-8 (IL-8). RESULTS: Datasets from two sepsis cohort studies with a total of 585 consecutive sepsis patients admitted to two intensive care units were downloaded as the training cohort (n = 479) and external validation cohort (n = 106). In the training cohort, 15 molecules, 20 pathways and 4 immune cells were eventually enrolled in model construction. These prognostic factors mainly reflected hypoxia, cellular injury, metabolic disorders and immune dysregulation in sepsis patients. In the validation cohort, the AUCs of the molecular model, pathway model, immune model, and combined model were 0.81, 0.82, 0.62 and 0.873, respectively. The AUCs of the traditional biomarkers (PCT and IL-8) were 0.565 and 0.585, respectively. The survival analysis indicated that patients in the high-risk group identified by models in the current study had a poor prognosis (P < 0.05). The above results indicated that the models in this study are all superior to the traditional biomarkers for the predicting the prognosis of sepsis patients. Furthermore, the current study provides some therapeutic recommendations for patients with high risk scores identified by the three submodels. CONCLUSIONS: In summary, the present study provides opportunities for bedside tests that could quantitatively and rapidly measure heterogeneous prognosis, underlying biological pathway variations and immune dysfunction in sepsis patients. Further therapeutic recommendations for patients with high risk scores could improve the therapeutic system for sepsis.


Assuntos
Escores de Disfunção Orgânica , Sepse/imunologia , Sepse/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Sepse/diagnóstico , Adulto Jovem
10.
J Thorac Oncol ; 17(4): 544-557, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34923163

RESUMO

INTRODUCTION: Camrelizumab, a humanized immunoglobulin G4-κ monoclonal antibody against programmed cell death protein 1, has exhibited antitumor activity and tolerability across various tumors, including lung cancers. We conducted this double-blind, randomized phase 3 trial to investigate the efficacy and safety of camrelizumab or placebo plus chemotherapy as first-line treatment for patients with advanced squamous NSCLC. The predictive value of circulating tumor DNA (ctDNA) dynamics was also analyzed. METHODS: CameL-sq, a double-blind, randomized phase 3 trial (NCT03668496), was conducted in 53 centers in the People's Republic of China. A total of 389 patients with stage IIIB-IV squamous NSCLC were randomized (1:1) to receive 4 to 6 cycles of carboplatin plus paclitaxel with camrelizumab or placebo (every 3 wk), followed by maintenance therapy with camrelizumab or placebo. Peripheral blood ctDNA samples were collected at baseline and the time after two cycles of treatment. RESULTS: Of 389 eligible patients, 193 patients allocated camrelizumab plus chemotherapy and 196 patients allocated placebo plus chemotherapy were included in the efficacy and safety analysis. The results revealed significantly prolonged progression-free survival (median, 8.5 vs. 4.9 mo; p <0.0001) and overall survival (median, not reached vs. 14.5 mo; p <0.0001) with camrelizumab-chemotherapy versus placebo-chemotherapy. No unexpected treatment immune-related adverse events were observed in both groups. Biomarker analysis revealed that ctDNA clearance after two cycles of treatment was independently associated with dramatically longer progression-free survival (p <0.0001) and overall survival (p <0.0001) in camrelizumab plus chemotherapy group. CONCLUSIONS: Our findings support camrelizumab plus chemotherapy as a first-line treatment option in advanced squamous NSCLC. On-treatment ctDNA dynamics exhibited the potency to predict the efficacy of camrelizumab plus chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Animais , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camelus , Carboplatina , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/patologia , Paclitaxel
11.
Front Med (Lausanne) ; 8: 727910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513888

RESUMO

Object: The fluid management strategy in ARDS is not very clear. A secondary analysis of RCT data was conducted to identify patients with ARDS benefitting from a conservative strategy of fluid management. Methods: The data of this study were downloaded from the ARDS network series of randomized controlled trials (Conservative Strategy vs. Liberal Strategy in 2006). Based on the clinical feature of patients, within the first 24 h after admission, clustering was performed using the k-means clustering algorithm to identify the phenotypes of ARDS. Survival was analyzed using the Kaplan-Meier survival analysis to assess the effect of the two fluid management strategies on the 90-day cumulative mortality. Categorical/dichotomic variables were analyzed by the chi-square test. Continuous variables were expressed as the mean and standard deviation and evaluated through a one-way ANOVA. A P-value < 0.05 was defined as the statistically significant cut-off value. Results: A total of 1,000 ARDS patients were enrolled in this unsupervised clustering research study, of which 503 patients were treated with a conservative fluid-management strategy, and 497 patients were treated with a liberal fluid-management strategy. The first 7-day cumulative fluid balance in patients with the conservative strategy and liberal strategy were -136 ± 491 ml and 6,992 ± 502 ml, respectively (P < 0.001). Four phenotypes were found, and the conservative fluid-management strategy significantly improved the 90-day cumulative mortality compared with the liberal fluid-management strategy (HR = 0.532, P = 0.024) in patients classified as "hyperinflammatory anasarca" phenotype (phenotype II). The characteristics of this phenotype exhibited a higher WBC count (20487.51 ± 7223.86/mm3) with a higher incidence of anasarca (8.3%) and incidence of shock (26.6%) at baseline. The furthermore analysis found that the conservative fluid management strategy was superior to the liberal fluid management strategy in avoiding superinfection (10.10 vs. 14.40%, P = 0.037) and returned to assisted breathing (4.60 vs. 16.20%, P = 0.030) in patients classified as "hyperinflammatory anasarca" phenotype. In addition, patients with other phenotypes given the different fluid management strategies did not show significant differences in clinical outcomes. Conclusion: Patients exhibiting a "hyperinflammatory anasarca" phenotype could benefit from a conservative fluid management strategy.

12.
Open Med (Wars) ; 15(1): 723-727, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33336029

RESUMO

In December 2019, novel coronavirus pneumonia-19 (COVID-19) was discovered in the viral pneumonia cases that occurred in Wuhan, China, and then quickly spread around the world. This report described the clinical course of two COVID-19 patients and the purpose of the study was to discuss the combination of chest CT and clinical features for diagnosis of COVID-19. The first case was a typical COVID-19 case. A 66-year-old female presented to our hospital with a 3-day history of fever. She had contact with a COVID-19 patient. Chest CT showed a typical COVID-19 appearance. She was diagnosed with COVID-19 by a positive nucleic acid test. The second case was a 50-year-old male with a 2-day history of fever. He denied having been to Wuhan. Chest CT also showed typical features of COVID-19 pneumonia. COVID-19 nucleic acid tests were repeated up to seven times and the results remained controversial. Eventually, he was diagnosed with COVID-19. Our study shows that chest CT has high sensitivity for diagnosis of COVID-19 in clinical practice, particularly when the nucleic acid test is negative. The chest CT should be considered as a diagnostic tool for the COVID-19 screening, comprehensive evaluation, and follow-up and patients would benefit from effective treatments in time.

13.
Org Lett ; 20(18): 5680-5683, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30188133

RESUMO

A dramatic N-substituent controlled tandem annulation of 2-(2-(2-bromoethyl)phenyl)-1-sulfonylaziridines with 1,3-dicarbonyl compounds has been developed. When the N-substituent was a 4-methylbenzenesulfonyl group (Ts), sequential ring opening of aziridines, nucleophilic substitution, and lactamization took place to provide a series of hexahydrobenz[ e]isoindole compounds in good yields with good diastereoselectivities. By contrast, 3-benzazepine compounds were afforded in good yields via ring opening of aziridines and nucleophilic substitution when the N-substituent was the 4-nitrobenzenesulfonyl group (Ns).

14.
Zhongguo Zhen Jiu ; 37(9): 918-24, 2017 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-29354910

RESUMO

OBJECTIVE: To evaluate the effect of individualized scalp acupuncture base on location of brain function for motor dysfunction in stroke patients. METHODS: A total of 180 patients were randomly assigned into an individualized scalp acupuncture (ISA) group, a conventional scalp acupuncture (CSA) group and a rehabilitation group, 60 cases in each one. In the ISA group, we stimulated Sishencong (EX-HN 1), motor area and balance area, matched with pre-motor area for higher muscle tension, application area and NIE 's three-needle for involuntary motion, application area for poor motor coordination, forehead five-needle for cognitive disorder, sensory area for sensory disturbance. In the CSA group, the affected Dingnieqianxiexian (MS 6), Dingniehouxiexian (MS 7) and Zhenxiapangxian (MS 14) were selected. Rehabilitation was used during needle retained in the two groups. Simple rehabilitation was used in the rehabilitation group. All the treatment was given from Monday to Friday for 4 weeks, once a day for 20 times. Eight-week follow-up was applied. The Fugl-Meyer assessment (FMA) for motor function, modified Barthel Index (MBI) were used to evaluate clinical effect. RESULTS: After treatment and at follow-up, FMA and MBI scores increased compared with those before treatment in the three groups(all P<0.01), with significant differences among the three groups (all P<0.000 1) and better results in the ISA group compared with those in the other two groups (P<0.05, P<0.01) at the two time points. The FMA and MBI scores in the CSA group were higher than those in the rehabilitation group after treatment and at follow-up (all P<0.05). CONCLUSION: The individualized scalp acupuncture can improve motor dysfunction and self-care ability of daily life for stroke patients.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura/métodos , Couro Cabeludo , Reabilitação do Acidente Vascular Cerebral/métodos , Humanos , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
15.
Mol Cell Biochem ; 412(1-2): 91-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26608181

RESUMO

Hypoxia-induced pulmonary arterial hypertension (HPAH) is a refractory disease characterized by increased proliferation of pulmonary vascular smooth cells and progressive pulmonary vascular remodeling. The level of nitric oxide (NO), a potential therapeutic vasodilator, is low in PAH patients. L-arginine can be converted to either beneficial NO by nitric oxide synthases or to harmful urea by arginase. In the present study, we aimed to investigate whether an arginase inhibitor, S-(2-boronoethyl)-L-cysteine ameliorates HPAH in vivo and vitro. In a HPAH mouse model, we assessed right ventricle systolic pressure (RVSP) by an invasive method, and found that RSVP was elevated under hypoxia, but was attenuated upon arginase inhibition. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic conditions, and their proliferative capacity was determined by cell counting and flow cytometry. The levels of cyclin D1, p27, p-Akt, and p-ERK were detected by RT-PCR or Western blot analysis. Compared to hypoxia group, arginase inhibitor inhibited HPASMCs proliferation and reduced the levels of cyclin D1, p-Akt, p-ERK, while increasing p27 level. Moreover, in mouse models, compared to control group, hypoxia increased cyclin D1 expression but reduced p27 expression, while arginase inhibitor reversed the effects of hypoxia. Taken together, these results suggest that arginase plays an important role in increased proliferation of HPASMCs induced by hypoxia and it is a potential therapeutic target for the treatment of pulmonary hypertensive disorders.


Assuntos
Arginase/antagonistas & inibidores , Hipóxia Celular , Inibidores Enzimáticos/farmacologia , Hipertensão Pulmonar/prevenção & controle , Artéria Pulmonar/metabolismo , Animais , Células Cultivadas , Humanos , Hipertensão Pulmonar/etiologia , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Artéria Pulmonar/patologia , Remodelação Vascular
16.
Virol J ; 12: 168, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26467854

RESUMO

BACKGROUND: The dominant viral etiologies responsible for acute respiratory infections (ARIs) are poorly understood, particularly among hospitalized patients. Improved etiological insight is needed to improve clinical management and prevention of ARIs. METHODS: Clinical and demographic information and throat swabs were collected from 607 patients from 2011 to 2013 in Shandong Province, China. Multiplex RT-PCR (SeeplexTM RV detection, Seegene) was performed to detected 12 respiratory viral pathogens. RESULTS: A total of 607 hospitalized patients were enrolled from 2011 to 2013. Viruses were identified in 35.75 % (217/607) of cases, including 78 influenza virus A and B (IVA and IVB), 47 para-influenza viruses (PIVs), 41 respiratory syncytial virus (RSV) and 38 adenovirus (ADV). For the children under 15 year old, the common detected viruses were influenza viruses, RSV, PIVS and ADV, while the principal respiratory viruses were human coronaviruses (HCoV), PIVs, influenza viruses for the old adults. Co-infections with multiple viruses were detected in 15.67 % of patients. Children under 5 years were more likely to have one or more detectable virus associated with their ARI. The peak of ARI caused by the respiratory viruses occurred in winter. CONCLUSION: This study demonstrated respiratory viruses were the major cause of hospitalized ARI patients in Shandong Province, influenza virus was the most common detected, RSV was the highest incidence among the young children (≤5 years). These findings also gave a better understand of virus distribution among different age and seasons, which help to consider potential therapeutic approaches and develop effective prevention strategies for respiratory virus infection.


Assuntos
Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Viroses/epidemiologia , Viroses/virologia , Vírus/classificação , Vírus/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Hospitalização , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Faringe/virologia , Estações do Ano , Adulto Jovem
17.
BMC Infect Dis ; 15: 143, 2015 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-25885096

RESUMO

BACKGROUND: After the 2009 influenza A(H1N1)pdm09 pandemic, China established its first severe acute respiratory infections (SARI) sentinel surveillance system. METHODS: We analyzed data from SARI cases in 10 hospitals in 10 provinces in China from February 2011 to October 2013. RESULTS: Among 5,644 SARI cases, 330 (6%) were influenza-positive. Among these, 62% were influenza A and 38% were influenza B. Compared with influenza-negative cases, influenza-positive SARI cases had a higher median age (20.0 years vs.11.0, p=0.003) and were more likely to have at least one underlying chronic medical condition (age adjusted percent: 28% vs. 25%, p<0.001). The types/subtypes of dominant strains identified by SARI surveillance was almost always among dominant strains identified by the influenza like illness (ILI) surveillance system and influenza activity in both systems peaked at the same time. CONCLUSIONS: Data from China's first SARI sentinel surveillance system suggest that types/subtypes of circulating influenza strains and epidemic trends among SARI cases were similar to those among ILI cases.


Assuntos
Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/epidemiologia , Vigilância de Evento Sentinela , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
18.
Tumori ; 101(1): 111-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25702679

RESUMO

AIMS AND BACKGROUND: Lung cancer is characterized by uncontrolled cell growth in the lung tissue. A major challenge in cancer research is the biological interpretation of the complexity of cancer somatic mutation profiles. This study examines the role of pathway crosstalk in the metastatic process of lung cancer cells based on DNA microarray analysis. METHODS: We downloaded the gene expression profile GSE10096 from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified and the gene functions of selected DEGs were further analyzed. After KEGG pathway analysis, dysfunctional pathways and dysfunctional crosstalk between pathways in two types of lung cancer cells (low metastasis, M1, and high metastasis, M5) were examined. RESULTS: A total of 13433 genes were filtered as DEGs, and after pathway analysis, 108 signaling pathways related to cancer signaling pathways were screened, including a host pathway hsa05223 and 79 neighbor pathways. Dysfunctional crosstalk analysis of pathways revealed that pathway crosstalk dysfunction of M1 and M5 cells mainly occurred between hsa05223 (non-small cell lung cancer) and hsa04310 (Wnt signaling pathway), and between non-small cell lung cancer and hsa04520 (adherens junction), respectively. Significant pathway crosstalk dysfunction also existed between adherens junction and other classical signaling pathways such as hsa04110 (cell cycle), hsa04310 (Wnt signaling pathway), hsa04350 (TGF-beta signaling pathway), and hsa04630 (Jak-STAT signaling pathway). CONCLUSIONS: Our discovery will help to elucidate the molecular mechanisms of the high carcinogenic and metastatic potential of lung cancer cells. In addition, it will pave the way to developing effective therapies for lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Perfilação da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Receptor Cross-Talk , Transdução de Sinais , Regulação Neoplásica da Expressão Gênica , Humanos , Análise em Microsséries
19.
Inflammation ; 37(6): 2099-105, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25028099

RESUMO

Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma.


Assuntos
Remodelação das Vias Aéreas/fisiologia , Asma/metabolismo , Asma/patologia , Interleucinas/biossíntese , Adulto , Remodelação das Vias Aéreas/efeitos dos fármacos , Animais , Células Cultivadas , Citocinas/biossíntese , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Adulto Jovem
20.
Clin Dev Immunol ; 2013: 869521, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23690828

RESUMO

Our study investigated the epidemiology of respiratory viruses in adult patients with upper respiratory tract infection (URTI) between August 2009 and September 2010 in Jinan, northern China. Nasal and throat swabs (n = 596) were collected from adult patients with URTIs. Nine respiratory-related viruses, including IFV, PIV, HRV, HMPV, HBoV, HCoV, ADV, RSV, and EV, were detected in all samples by conventional and reverse transcription polymerase chain reactions. Positive detection rate for respiratory virus was 38.76% and codetection rate was 4.70% in adults with acute respiratory tract infections. IFV (20.81%) was the dominant agent detected and IFVB had a higher incidence (12.58%) than IFVA (7.72%). Detection rates of 8.22%, 5.03%, 3.69%, and 2.52% were observed for HBoV, HRV, EV, and RSV, respectively. HCoV had the lowest detection rate of 0.50%. HBoV, HRV, EV, and ADV infection rates were higher in the 14-25-year-old group than in the 26-65-year-old group. Codetection rates were higher (7.52%) in the 14-25-year-old group than in the older age group (2.64%). The spectrum of respiratory virus infection in adult patients with URTIs was different in Jinan compared with other cities in China.


Assuntos
Influenza Humana/epidemiologia , Infecções por Parvoviridae/epidemiologia , Infecções por Picornaviridae/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Comorbidade , Feminino , Bocavirus Humano/isolamento & purificação , Humanos , Influenza Humana/diagnóstico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Orthomyxoviridae/isolamento & purificação , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/virologia , Infecções por Picornaviridae/diagnóstico , Infecções por Picornaviridae/virologia , Prevalência , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Rhinovirus/isolamento & purificação
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