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1.
Artigo em Inglês | MEDLINE | ID: mdl-34777533

RESUMO

Objective: This meta-analysis was conducted to compare the therapeutic efficacy and clinical safety of the combination therapy of apatinib plus chemotherapy with that of chemotherapy alone in patients with refractory or recurrent ovarian carcinoma (OC). Methods: Relevant randomized controlled trials (RCT) or case-control studies (CCS) were identified by searching Chinese and English databases up to October 31, 2020. The risk of methodological bias tool and Newcastle-Ottawa scale (NOS) were used to assess trial quality. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the therapeutic effects and adverse drug reactions. Subgroup analyses of study type, study sample size, dosage of apatinib, and chemotherapy regimen between treatment group and control group were performed. Publication bias was assessed by funnel plot symmetry, Begg-Mazumdar test, and Egger test. The robustness of our results was presented by removing the trial one by one. Results: Fifteen eligible studies covering 1,020 patients were included in this review and meta-analysis. Among these studies, 8 were RCTs, and 7 were CCSs. Compared with chemotherapy alone, apatinib plus chemotherapy significantly increased objective response rate (OR = 3.55; 95% CI 2.31 to 5.47), disease control rate (OR = 3.04; 95% CI 2.12 to 4.36), and overall survival (OR = 5.03; 95% CI 3.16 to 6.90). Conclusions: The combination treatment of apatinib plus chemotherapy provides better clinical benefits for OC patients when compared to chemotherapy alone and should be recommended for suitable patients with OC after the failure of standard regimens. However, further investigation into future large-scale prospective randomized research is still needed.

2.
Opt Express ; 29(20): 32006-32019, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615280

RESUMO

Quantum nonlinear interferometers (QNIs) can measure the infrared physical quantities of a sample by detecting visible photons. A QNI with Michelson geometry based on the spontaneous parametric down-conversion in a second-order nonlinear crystal is studied systematically. A simplified theoretical model of the QNI is presented. The interference visibility, coherence length, equal-inclination interference, and equal-thickness interference for the QNI are demonstrated theoretically and experimentally. As an application example of the QNI, the refractive index and the angle between two surfaces of a BBO crystal are measured using equal-inclination interference and equal-thickness interference.

3.
Pulm Circ ; 11(4): 20458940211051292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659741

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important and major player in the pathophysiology of hypercholesterolemia and atherosclerosis. Recently, PCSK9 has been implicated in the pathogenesis of inflammatory diseases. Whether PCSK9 is involved in idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to investigate the relationship between PCSK9 and IPAH. Serum PCSK9, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1ß), and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme linked immunosorbent assay. Transthoracic echocardiography was performed among 40 IPAH patients and 20 control subjects. Hemodynamic data were collected via right heart catheterization in patients with IPAH. Serum PCSK9, TNF-α, IL-6, IL-1ß, and MCP-1 levels were significantly higher in IPAH patients than in control subjects (p < 0.001). Among enrolled IPAH patients, PCSK9 levels were higher in WHO-FC III/IV patients compared with those in WHO-FC I/II (p < 0.05), and were positively correlated with TNF-α, IL-6, MCP-1, N-Terminal pro-brain natriuretic peptide, pulmonary arterial systolic pressure (r = 0.653, p < 0.001), pulmonary arterial diastolic pressure (r = 0.466, p = 0.002), mean pulmonary arterial pressure (mPAP, r = 0.730, <0.001), pulmonary vascular resistance (r = 0.488, p = 0.001), and right ventricle diameter (r = 0.563, p < 0.001). In multiple regression analysis, mPAP was strongly associated with serum PCSK9 (ß = 0.694, p < 0.001), independent of other variables. Receiver operating characteristic curve analysis showed the optimal cutoff value of serum PCSK9 concentration for predicting IPAH was 90.67 ng/ml, with a sensitivity of 90.0% and a specificity of 85.0%. In conclusion, IPAH patients had elevated serum PCSK9 levels which correlated the presence and severity of pulmonary hypertension. PCSK9 may be a novel potential therapeutic target.

4.
Sci Immunol ; 6(58)2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931568

RESUMO

Pharmacologically inhibiting nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome activation results in potent therapeutic effects in a wide variety of preclinical inflammatory disease models. NLRP3 deubiquitination is essential for efficient NLRP3 inflammasome activity, but it remains unclear whether this process can be harnessed for therapeutic benefit. Here, we show that thiolutin (THL), an inhibitor of the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease, blocks NLRP3 inflammasome activation by canonical, noncanonical, alternative, and transcription-independent pathways at nanomolar concentrations. In addition, THL potently inhibited the activation of multiple NLRP3 mutants linked with cryopyrin-associated periodic syndromes (CAPS). Treatment with THL alleviated NLRP3-related diseases in mouse models of lipopolysaccharide-induced sepsis, monosodium urate-induced peritonitis, experimental autoimmune encephalomyelitis, CAPS, and methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Mechanistic studies revealed that THL inhibits the BRCC3-containing isopeptidase complex (BRISC)-mediated NLRP3 deubiquitination and activation. In addition, we show that holomycin, a natural methyl derivative of THL, displays an even higher inhibitory activity against NLRP3 inflammasome than THL. Our study validates that posttranslational modification of NLRP3 can be pharmacologically targeted to prevent or treat NLRP3-associated inflammatory diseases. Future clinical development of derivatives of THL may provide new therapies for NLRP3-related diseases.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33790982

RESUMO

Objective: This study aimed to find new biomarkers of prognosis and metabolomic therapy for gastric carcinoma (GC) treated with chemotherapy and investigate the metabolic mechanism of the Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction in the treatment of GC. Methods: First, 36 patients with GC were randomly assigned to the treatment (chemotherapy plus JPYZXZ) and control (chemotherapy alone) groups. The clinical efficacy, side effects, and quality of life of patients in the two groups were evaluated after treatment. Then, the serum samples taken from 16 randomly selected patients (eight treatment cases and eight control cases with no evident pattern characters) and eight healthy volunteers were tested to identify the differential metabolite under the gas chromatography-time-of-fight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. Results: JPYZXZ combined with chemotherapy resulted in a lower risk of leucopenia, thrombocytopenia, and gastrointestinal reaction (P < 0.05). Additionally, patients in the treatment group showed a higher Karnofsky (KPS) scale (P < 0.05). Compared with healthy persons, patients with GC were found to have 26 significant differential metabolites after chemotherapy; these metabolites are mainly involved in 12 metabolic pathways, such as valine, leucine, and isoleucine biosynthesis. JPYZXZ primarily influences the pentose phosphate pathway; glutathione metabolism; glyoxylate and dicarboxylate metabolism; porphyrin and chlorophyll metabolism; and glycine, serine, and threonine metabolism of patients with GC treated with chemotherapy. Conclusions: The metabolic characteristics of patients with GC after chemotherapy are mainly various amino acid metabolic defects, especially L-glutamine, L-leucine, L-alloisoleucine, and L-valine. These defects lead to a series of problems, such as decreased tolerance and effectiveness of chemotherapy, increased side effects, decreased immunity, and shortened survival time. In addition, the remarkable upregulation of the gluconolactone level in patients with GC suggests the high proliferative activity of GC cells. Thus, gluconolactone may be used as a potential prognostic and diagnostic evaluation index. Moreover, JPYZXZ can reduce the incidence of ADRs and improve the life quality of patients by the correction of L-glutamine, L-leucine, L-alloisoleucine, and L-valine metabolism deficiency. In addition, gluconolactone metabolism is inhibited by JPYZXZ. Such inhibition may be one of the antitumor mechanisms of JPYZXZ.

6.
Intern Med J ; 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33813804

RESUMO

BACKGROUND: Information on rhabdomyolysis-associated acute kidney injury (AKI) in the emergency department or general ward is limited. AIM: We assessed the risk factors, outcomes, and clinical correlates with intensive care unit (ICU) transfer among patients with rhabdomyolysis-associated AKI. METHODS: Patients with rhabdomyolysis were divided into the rhabdomyolysis-associated AKI group and the rhabdomyolysis without AKI group. In-hospital outcomes, including ICU transfer, mortality, length of stay, daily cost and renal recovery were analyzed. Multivariate regression analysis was performed to identify the association between rhabdomyolysis-associated AKI and ICU transfer. RESULTS: Among 149 patients with rhabdomyolysis, 68 (45.6%) developed AKI. Age and urine protein were important risk factors for rhabdomyolysis-associated AKI. Patients with rhabdomyolysis-associated AKI had higher levels of undergoing dialysis (19.1% versus 2.5%, p < 0.01), all-cause mortality (13.2% versus 1.2%, p < 0.01), cost of hospitalization [10.8 1,000 yuan, IQR (5.5, 3.5) versus 5.9 1,000 yuan, IQR 5.9 (3.6, 9.9), p = 0.03], as well as longer length of hospital stay [8.0 days (5.0, 14.0)] versus [6.0 days (4.0, 11.0)], p = 0.02). Additionally, the percentage of patients with AKI who transferred to ICU was higher than patients without AKI (33.8% versus 12.3%, p < 0.002) and rhabdomyolysis-associated AKI was an independent risk factor for ICU transfer (adjusted odds ratio [OR] = 2.58, 95% confidence interval [CI], 1.12-6.8, p = 0.03). CONCLUSION: Rhabdomyolysis-associated AKI was common in the emergency department or general ward and led to more severe outcomes. It was also associated with the risk of ICU transfer. This article is protected by copyright. All rights reserved.

7.
J Transl Med ; 19(1): 150, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858440

RESUMO

BACKGROUND: Sidedness (right/left) of colorectal cancer (CRC) is essential for treatment. Whether carcinogenesis of tobacco varies by sidedness remains unclear. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis. METHODS: In the multi-center retrospective study, data on 46 166 Chinese CRC patients were extracted from a big-data platform. Logistic regression analyses were performed to evaluate qualitative and quantitative associations between smoking and tumor sidedness. Survival analyses were conducted in metastatic CRC. RESULTS: History of smoking was associated with left-sided CRC (LSCRC; Adjusted odds ratio, 1.25; 95% CI, 1.16 - 1.34; P < .001). The sidedness tendency towards LSCRC increased from non-smokers, to ex-smokers, and to current smokers (P for trend < .001). Longer duration (P for trend < .001) and larger total amount of cigarette smoking (P for trend < .001) were more associated with LSCRC, respectively. The association was confirmed in both left-sided colon cancer and rectal cancer, but was stronger for rectal cancer (P = .016). Alcoholism significantly enhanced the association by 7% (P = .027). Furthermore, prognostic advantage of metastatic LSCRC diminished among ever-smokers, with contrary survival impacts of smoking on either side of CRC. CONCLUSIONS: History of smoking was associated with LSCRC in a positive dose-response relationship, and presented opposite prognostic impacts on right- and left-sided tumors. Smoking potentially plays an instrumental role in the mechanism for sidedness heterogeneity in CRC.


Assuntos
Fumar Cigarros , Neoplasias do Colo , Neoplasias Colorretais , Humanos , Estudos Retrospectivos , Tabaco
8.
World J Emerg Med ; 12(1): 48-53, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505550

RESUMO

BACKGROUND: This study aims to investigate whether small balloon aortic valvuloplasty (BAV) reduces the need for permanent pacemaker implantation (PPMI) after transcatheter aortic valve implantation (TAVI). METHODS: This was a retrospective analysis using data from our local TAVI database. Small BAV was defined as a small balloon size (=18 mm) pre-dilatation. Normal BAV was defined as a balloon size >18 mm. The primary endpoint was the incidence of new PPMI. RESULTS: Of 99 consecutive TAVI patients, five patients were excluded due to pre-existing permanent pacemaker. Patients in the small BAV group (n=57) had a significantly lower PPMI rate compared with the normal BAV group (n=37) (3.5% vs. 18.9%, P=0.026). Moderate or severe aortic valve regurgitation post-procedure was similar between the small BAV and normal BAV groups (5.3% vs. 8.1%, P=0.480); likewise, the mean aortic gradient post-procedure did not differ significantly (11.5±5.2 mmHg vs. 12.2±7.3 mmHg, 1 mmHg=0.133 kPa, P=0.580) between the groups. Device success rates were also similar (94.7% vs. 91.8%, P=0.680). In multivariable analysis, small BAV (P=0.027), the ratio of prosthesis diameter to annulus diameter (P=0.048), and mean aortic gradient by echo in the basement (P=0.021) were independent predictors of PPMI. CONCLUSIONS: The small BAV strategy is associated with a low rate of permanent pacemaker implantation after transcatheter self-expanding valve implantation in this single-center observational study.

9.
J Agric Food Chem ; 69(1): 88-100, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33356208

RESUMO

Insect resistance to insecticides is an increasingly serious problem, and the resistant mechanisms are complicated. The resistance research based on the chemosensory pathway is one of the hot problems at present, but the specific binding mechanism of chemosensory genes and insecticides remains elusive. The binding mechanism of AlepGOBP2 (belong to insect chemosensory gene) with two insecticides was investigated by computational and experimental approaches. Our calculation results indicated that four key residues (Phe12, Ile52, Ile94, and Phe118) could steadily interact with these two insecticides and be assigned as hotspot sites responsible for their binding affinities. The significant alkyl-π and hydrophobic interactions involved by these four hotspot residues were found to be the driving forces for their binding affinities, especially for two residues (Phe12 and Ile94) that significantly contribute to the binding of chlorpyrifos, which were also validated by our binding assay results. Furthermore, we also found that the AlepGOBP2-chlorpyrifos/phoxim complexes can be more efficiently converged in the residue-specific force field-(RSFF2C) and its higher accuracy and repeatability in protein dynamics simulation, per-residue free energy decomposition, and computational alanine scanning calculations have also been achieved in this paper. These findings provided useful insights for efficient and reliable calculation of the binding mechanism of relevant AlepGOBPs with other insecticides, facilitating to develop new and efficient insecticides targeting the key sites of AlepGOBP2.


Assuntos
Clorpirifos/química , Proteínas de Insetos/química , Mariposas/metabolismo , Compostos Organotiofosforados/química , Receptores Odorantes/química , Receptores Odorantes/metabolismo , Animais , Clorpirifos/metabolismo , Proteínas de Insetos/metabolismo , Simulação de Dinâmica Molecular , Mariposas/química , Compostos Organotiofosforados/metabolismo , Ligação Proteica
10.
Travel Med Infect Dis ; 39: 101950, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33307197

RESUMO

BACKGROUND: To investigate and compare the clinical and imaging features among family members infected with COVID-19. METHODS: We retrospectively collected a total of 34 COVID-19 cases (15 male, 19 female, aged 48 ± 16 years, ranging from 10 to 81 years) from 13 families from January 17, 2020 through February 15, 2020. Patients were divided into two groups: Group 1 - part of the family members (first-generation) who had exposure history and others (second-generation) infected through them, and Group 2 - patients from the same family having identical exposure history. We collected clinical symptoms, laboratory findings, and high-resolution computed tomography (HRCT) features for each patient. Comparison tests were performed between the first- and second-generation patients in Group 1. RESULTS: In total there were 21 patients in Group 1 and 20 patients in Group 2. For Group 1, first-generation patients had significantly higher white blood cell count (6.5 × 109/L (interquartile range (IQR): 4.9-9.2 × 109/L) vs 4.5 × 109/L (IQR: 3.7-5.3 × 109/L); P = 0.0265), higher neutrophil count (4.9 × 109/L (IQR: 3.6-7.3 × 109/L) vs 2.9 × 109/L (IQR: 2.1-3.3 × 109/L); P = 0.0111), and higher severity scores on HRCT (3.9 ± 2.4 vs 2.0 ± 1.3, P = 0.0362) than the second-generation patients. Associated underlying diseases (odds ratio, 8.0, 95% confidence interval: 3.4-18.7, P = 0.0013) were significantly correlated with radiologic severity scores in second-generation patients. CONCLUSION: Analysis of the family cluster cases suggests that COVID-19 had no age or sex predominance. Secondarily infected patients in a family tended to develop milder illness, but this was not true for those with existing comorbidities.


Assuntos
COVID-19/patologia , Família , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/transmissão , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
11.
Mil Med Res ; 7(1): 41, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887670

RESUMO

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.


Assuntos
Quimioprevenção/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Betacoronavirus , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Alta do Paciente/normas , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , SARS-CoV-2
12.
Endocrinology ; 161(10)2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877513

RESUMO

The free fatty acid receptor G protein-coupled receptor 120 (GPR120) is expressed in pancreatic islets, but its specific cell distribution and function have not been fully established. In this study, a GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhanced green fluorescence proteins (EGFP). EGFP-positive cells collected from KI mouse islets by flow cytometry had a significantly higher expression of pancreatic polypeptide (PP) evidenced by reverse transcriptase (RT)-quantitative polymerase chain reaction (qPCR). Single-cell RT-PCR and immunocytochemical double staining also demonstrated the coexpression of GPR120 with PP in mouse islets. The GPR120-specific agonist TUG-891 significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR120 small interfering RNA treatment. TUG-891-stimulated PP secretion in islets was fully blocked by pretreatment with YM-254890 (a Gq protein inhibitor), U73122 (a phospholipase C inhibitor), or thapsigargin (an inducer of endoplasmic reticulum Ca2+ depletion), respectively. TUG-891 triggered the increase in intracellular free Ca2+ concentrations ([Ca2+]i) in PP cells, which was also eliminated by YM-254890, U73122, or thapsigargin. GPR120 gene expression was significantly reduced in islets of high-fat diet (HFD)-induced obese mice. TUG-891-stimulated PP secretion was also significantly diminished in vivo and in vitro in HFD-induced obese mice compared with that in normal-chow diet control mice. In summary, this study demonstrated that GPR120 is expressed in mouse islet PP cells and GPR120 activation stimulated PP secretion via the Gq/PLC-Ca2+ signaling pathway in normal-chow diet mice but with diminished effects in HFD-induced obese mice.


Assuntos
Cálcio/metabolismo , Ilhotas Pancreáticas/metabolismo , Polipeptídeo Pancreático/metabolismo , Receptores Acoplados a Proteínas G/fisiologia , Fosfolipases Tipo C/metabolismo , Animais , Compostos de Bifenilo/farmacologia , Células Cultivadas , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenilpropionatos/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fosfolipases Tipo C/fisiologia
13.
Mil. med. res. (Lond.) ; 7(41): 1-33, Sept. 04, 2020.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1129883

RESUMO

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients


Assuntos
Humanos , Adulto , Plasma/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Cloroquina/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Quimioprevenção/métodos , Receptores de Interleucina-6/uso terapêutico , Antirretrovirais/uso terapêutico , Pandemias/prevenção & controle , Lopinavir/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Hidroxicloroquina/uso terapêutico , Prática Clínica Baseada em Evidências/métodos
14.
Ann Transl Med ; 8(14): 860, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32793704

RESUMO

Background: Tumor mutation burden (TMB) has an important association with immunotherapy responses. TMB in the Chinese population has not been well established. Finding differences between the Chinese and Caucasian populations and elucidating the underlying biological mechanisms of high TMB might help develop more precise and effective means for TMB and immunotherapy response prediction. Methods: Chinese cancer patients fresh tissue (n=2,177), formalin-fixed, paraffin-embed (FFPE) specimens (n=3,294), and pleural fluid (n=189) were profiled using a 295- or 520-gene next-generation sequencing (NGS) panel. The association of the TMB status with a series of molecular features and biological pathways was determined using bootstrapping. Results: TMB, measured by 295- or 520-cancer-related gene panels, was correlated with whole-exome sequencing (WES) TMB based on the in silico simulation in The Cancer Genome Atlas cohort. The median TMB of our data was slightly higher than that from the Foundation Medicine Inc. (FMI) dataset. TMB was also slightly different within the same cancer type between the Chinese and Caucasian population. We discovered that the underlying pathways of TMB status varied greatly and sometimes had an opposite association with TMB across different cancer types. Moreover, we developed a 23-gene and a 16-gene signature to predict TMB prediction for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively, indicating a histology-specific mechanism for driving high-TMB in lung cancer. Conclusions: TMB varies among different ethnic populations. Our findings extend the knowledge of the underlying biological mechanisms for high TMB and might be helpful for developing more precise and accessible TMB assessment panels and algorithms in more cancer types.

15.
J Agric Food Chem ; 68(22): 6092-6103, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32392414

RESUMO

Athetis lepigone is a polyphagous pest found around the world that feeds on maize, wheat, and various other important crops. Although it exhibits a degree of resistance to various chemical insecticides, an effective pest-control method has not yet been developed. The sex pheromone communication system plays an essential role in the mating and reproduction of moths, in which pheromone-binding proteins (PBPs) are crucial genes. In this study, we cloned and purified the protein AlepPBP1 using an E. coli expression system and found it had a higher binding affinity to two sex pheromones of A. lepigone, namely, Z7-12:Ac and Z9-14:Ac (with Ki 0.77 ± 0.10 and 1.10 ± 0.20 µM, respectively), than to other plant volatiles. The binding-mode analysis of protein conformation with equilibrium stabilization was obtained using molecular dynamics (MD) simulation and indicated that hydrophobic interactions involving several nonpolar residues were the main driving force for the binding affinity of AlepPBP1 with sex pheromones. Computational alanine scanning (CAS) was performed to further identify key amino acid residues and validate their binding contributions. Each key residue, including Phe36, Trp37, Val52, and Phe118, was subsequently mutated into alanine using site-directed mutagenesis. Binding assays showed that the efficient binding abilities to Z7-12:Ac (F36A, W37A, and F118A) and Z9-14:Ac (F36A, W37A, V52A, and F118A) were almost lost in the mutated proteins. Our results demonstrated that these key amino acid residues are crucial for determining the binding ability of AlepPBP1 to sex pheromones. These findings provide a basis for the use of AlepPBP1 in the studies as a specific target for the development of novel behavioral antagonists with marked inhibition or mating-disruption abilities using computer-aided drug design (CADD).


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Insetos/metabolismo , Mariposas/metabolismo , Atrativos Sexuais/metabolismo , Motivos de Aminoácidos , Animais , Proteínas de Transporte/química , Proteínas de Transporte/genética , Feminino , Proteínas de Insetos/química , Proteínas de Insetos/genética , Cinética , Masculino , Simulação de Acoplamento Molecular , Mariposas/química , Mariposas/efeitos dos fármacos , Mariposas/genética , Ligação Proteica , Atrativos Sexuais/química , Atrativos Sexuais/farmacologia
16.
J Hazard Mater ; 397: 122777, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32388456

RESUMO

Athetis lepigone is one of the most severe polyphagous pests, and it has developed resistance to different chemical insecticides. Insects primarily rely on the olfactory system to recognize various environmental chemicals, including xenobiotics such as insecticides. Here, we expressed two A. lepigone pheromone-binding proteins (AlepPBP2 and AlepPBP3), and observed they had higher binding affinities to phoxim than other insecticides, with Ki was 3.30 ±â€¯0.38 µM and 3.27 ±â€¯0.10 µM, respectively. Molecular dynamics simulation, binding mode analysis, and computational alanine scanning showed that six residues (Phe15, Phe39, Ile55, Leu65, Ile97, and Phe122) of AlepPBP2 and three residues (Phe12, Ile52, and Ile134) of AlepPBP3 maybe as potential residues that can change protein ability to bind an organophosphorus insecticide phoxim. Then, we used site-directed mutagenesis assay to mutate these residues into alanine, respectively. Subsequently, the binding assays displayed that Phe15, Phe39, and Ile97 of AlepPBP2, Phe12 and Ile134 of AlepPBP3 caused a significant decrease of AlepPBPs binding ability to phoxim, suggesting they should play crucial roles in the AlepPBPs/phoxim interactions. Our findings could further advance in using PBPs as unique targets to design and develop precise and environmentally-friendly pest control agents with high insecticidal potential using a computer-aided drug design (CADD) approach.


Assuntos
Inseticidas , Transtornos do Olfato , Animais , Proteínas de Transporte , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Inseticidas/toxicidade , Feromônios
17.
Mil Med Res ; 7(1): 17, 2020 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-32245396

RESUMO

On 6 February 2020, our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infection, and this guideline provided our experience and make well reference for fighting against this pandemic worldwide. However, the coronavirus disease 2019 (COVID-19) is a new disease, our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience; hence, the strategies of diagnosis and treatment are also continually updated. In this letter, we answered one comment on our guideline and provided the newest diagnostic criteria of "suspected case" and "confirmed case" according to the latest Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People's Republic of China.


Assuntos
Infecções por Coronavirus , Pneumonia Viral , Betacoronavirus , COVID-19 , China , Humanos , Pandemias , SARS-CoV-2
18.
Adv Ther ; 37(5): 2199-2209, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32239458

RESUMO

INTRODUCTION: To explore the relationship between serum high-density lipoprotein cholesterol (HDL-C) levels and the presence and severity of pulmonary arterial hypertension (PAH). METHODS: A total of 177 patients with PAH and 103 patients without pulmonary hypertension (PH) were enrolled in this study. All patients underwent right heart catheterization (RHC) for diagnosing and assessing the severity of PAH. Demographics, comorbidities, and laboratory data including serum HDL-C levels were collected. RESULTS: Plasma HDL-C levels in patients with PAH were significantly lower compared with patients without PH (1.08 ± 0.36 vs 1.49 ± 0.36, p < 0.001). HDL-C levels positively correlated with cardiac output (r = 0.360, p < 0.001), cardiac index (r = 0.337, p < 0.001), and mixed venous oxygen saturation (r = 0.426, p < 0.001), and negatively with mean pulmonary arterial pressure (r = - 0.529, p < 0.001), right atrial pressure (r = - 0.421, p < 0.001), and pulmonary vascular resistance (r = - 0.583, p < 0.001). Multivariate logistic regression analysis indicated that HDL-C was a significant independent predictor of PAH (OR 0.042, 95% CI 0.006-0.304, p = 0.002). The receiver operating characteristic curve analysis showed that the optimal cutoff value of the serum HDL-C concentration for predicting PAH was 1.32 mmol/L, with a sensitivity of 83.6% and a specificity of 72.8% (area under the curve 0.803, 95% confidence interval 0.750-0.856, p < 0.001). CONCLUSIONS: Serum HDL-C is a simple biomarker that might be used for prediction and assessment of PAH in Chinese Han ethnicity, and the mechanism underlying the association needs further study.


Assuntos
Biomarcadores/sangue , HDL-Colesterol/sangue , Hipertensão Arterial Pulmonar/sangue , Hipertensão Arterial Pulmonar/fisiopatologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
19.
Sheng Li Xue Bao ; 72(2): 175-180, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32328611

RESUMO

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.


Assuntos
Adipócitos/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Leptina/metabolismo , Células 3T3 , Adenilato Quinase , Animais , Regulação para Baixo , Sistema de Sinalização das MAP Quinases , Camundongos , Fosforilação , Transdução de Sinais
20.
Mil Med Res ; 7(1): 4, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029004

RESUMO

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Infecção Hospitalar , Controle de Infecções , Programas de Rastreamento , Equipamento de Proteção Individual , Pneumonia Viral , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Infecção Hospitalar/prevenção & controle , Diagnóstico Diferencial , Medicamentos de Ervas Chinesas , Medicina Baseada em Evidências , Hidratação , Humanos , Controle de Infecções/normas , Pulmão/diagnóstico por imagem , Epidemiologia Molecular , Cuidados de Enfermagem , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão , SARS-CoV-2
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