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1.
BMC Pulm Med ; 22(1): 425, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401235

RESUMO

PURPOSE: This national study aimed to investigate the lung ultrasound (LUS) training and practice of respiratory therapists (RTs) in mainland China. METHODS: A cross-sectional multicenter survey was conducted from May 22, 2021 to August 12, 2021, through online platforms. This survey included RTs in mainland China. The survey was divided into four sections: (1) demographic characteristics and basic information; (2) basic information about LUS training and practice; (3) LUS practice details; and (4) Other ultrasound training and practice. RESULTS: A total of 514 responses were received, and 494 valid responses were included in the analysis. 81.2% (401/494) participants' highest degree of education was a bachelor's degree, and 43.1% (213/494) participants were at level II in terms of job ranking. 99.2%(490/494) participants agreed that the RTs needed to learn lung ultrasound, but only 12.3% (61/494) participants had received a LUS training course. Further, 66.2% (327/494) experienced participants responded to Sect. 3. Most of RTs used LUS when the patient had hypoxia (265/327, 81%) or dyspnea (260/317, 79.5%); they also used it during spontaneous breathing trial(SBT) (191/327, 58.4%) or in prone position (177/327, 54.1%). The A-line (302/327, 92.4%), B-line (299/327, 91.4%), lung slide (263/327, 80.4%), and bat sign (259/327, 79.2%) were well known as LUS signs. Also, 30.6% (100/327) participants did not use the LUS protocol in their clinical practice, and only 25.4%(83/327) participants said they had used LUS scores. Moreover, 55.7% (182/327) participants frequently changed the respiratory therapy strategy according to LUS results. CONCLUSIONS: We should improve the number and workplace of RTs in mainland China in the future. We should also standardize the application of LUS practice and training for RTs in mainland China and establish corresponding certification pathways.


Assuntos
Pneumopatias , Pulmão , Humanos , Estudos Transversais , Ultrassonografia/métodos , Pulmão/diagnóstico por imagem , Terapia Respiratória
2.
Brain Sci ; 12(11)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36358384

RESUMO

Action processing is crucial for sports activities. Using event-related potentials (ERPs), the present study investigated whether semantics were activated in action processing and, if so, whether semantic activation was modulated by action duration. Badminton athletes were recruited to finish a lexical decision task following an action-semantic priming paradigm, in which short (400 ms) or long (1000 ms) action videos served as primes, and semantically congruent or incongruent action words served as targets. The ERP results showed a P300 effect, that is, larger P300 amplitudes were observed for targets primed by semantically incongruent action videos than for targets primed by semantically congruent action videos, only when the action videos were long and not when the action videos were short. Moreover, a late positive component (LPC) was only sensitive to action duration, showing that the targets primed by long action videos elicited larger LPC amplitudes compared to the targets primed by short action videos. These results suggested that semantics could be activated in action processing and that semantic activation was modulated by action duration, supporting a link between the language system and action processing.

3.
BMC Anesthesiol ; 22(1): 332, 2022 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-36309639

RESUMO

BACKGROUND: To explore whether hepatic vein systolic filling fraction (SFF) is associated with central venous pressure (CVP) and right ventricular (RV) systolic function in critically ill patients. METHODS: Adult patients admitted to ICU with echocardiographic examination were retrospectively enrolled. Echocardiographic parameters including hepatic vein systolic velocity (S) and diastolic phase velocity (D) and haemodynamic information at the time of echo examination were collected. RV systolic dysfunction was defined as tricuspid annular plane systolic excursion (TAPSE) < 16 mm. SFF was calculated as S/(S + D). RESULTS: Two hundred four patients were enrolled in this study among whom 40 patients had a CVP ≤5 mmHg, 110 patients had a CVP 6-9 mmHg and 54 patients had a CVP ≥10 mmHg. The three groups had similar S velocity, D velocity and SFF. No correlation between SFF and CVP was found (r = - 0.046, p = 0.500), but correlation between SFF and TAPSE was noticed (r = 0.468, p < 0.001). The ROC analysis showed that the area under curve (AUC) of SFF for determining CVP ≥10 mmHg was 0.513 (95% CI: 0.420-0.606, p = 0.775), but the AUC of SFF for determining RV systolic dysfunction was 0.759 (95% CI: 0.686-0.833, p < 0.001). CONCLUSION: Hepatic vein systolic filling fraction is associated with RV systolic function in critically ill patients and is not associated with CVP.


Assuntos
Disfunção Ventricular Direita , Adulto , Humanos , Pressão Venosa Central , Disfunção Ventricular Direita/diagnóstico por imagem , Estado Terminal , Estudos Retrospectivos , Veias Hepáticas/diagnóstico por imagem , Função Ventricular Direita
4.
Front Med (Lausanne) ; 9: 968133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186819

RESUMO

Purpose: Little epidemiological data exist on patients with severe infection in the plateau region of China, and the data that do exist are lacking in quality. Using the medical records of patients with severe infection in the Department of Intensive Medicine (intensive care unit; ICU) of the People's Hospital of Tibet Autonomous Region, this study analyzed the epidemiological and clinical characteristics of patients with septic shock in plateau area (Tibet), with the ultimate aim of reducing the incidence and mortality from this condition. Methods: Clinical data on 137 patients with septic shock in the studied ICU from November 2017 to October 2019 were retrospectively analyzed using SPSS, Version 21.0. Results: Among the 137 patients with septic shock, there were 47 survivors and 90 in-hospital or post-discharge deaths. There were 91 male patients and 46 female patients. The incidence of septic shock was 11.3%, and mortality rate was 65.7%. Median age was 55 years old, median APACHE-II score on the day of admission was 17, median SOFA score was 11, and median number of organ injuries was one. APACHE-II score (P = 0.02), SOFA score (P < 0.001), and the number of organ injuries (P < 0.001) were higher among patients who died than among survivors. The infections were mainly pulmonary and abdominal, and the main pathogen was gram-negative bacteria. Conclusion: The incidence and mortality of septic shock in ICU wards in Tibet are very high. The APACHE-II score, SOFA score, and the number of organ damage on the first day after diagnosis are independent risk factors for septic shock. To some extent, this study reflects the epidemiological characteristics of septic shock in the plateau region of China (≥ 3,650 m above sea level) and provides data that can support the prevention and treatment of sepsis in the future. More and deeper epidemiological studies of septic shock are necessary.

5.
Front Pediatr ; 10: 1018641, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263153

RESUMO

Background: The aim of our study was to develop a nomogram predicting the early failure rate of Pavlik harness in infants under 6 months of age with developmental dysplasia of the hip (DDH). Methods: We retrospectively analyzed the clinical data of 227 patients (372 hips) with DDH who were treated with Pavlik harness at our institution from August 2019 to January 2022. Fifty-eight patients (102 hips) failed the Pavlik harness treatment, and 169 patients (270 hips) were successfully treated. Then, the independent risk factors for treatment failure were determined via univariate and multivariate logistic regression and used to generate the nomogram predicting the failure rate of the Pavlik harness. Results: It was found that age at initial treatment (OR 1.031, 95% CI 1.022-1.040, P < 0.001), angle α (OR 0.723, 95% CI 0.671-0.779, P < 0.001), and concomitant deformity (OR 0.129, 95% CI 0.036-0.459, p = 0.002) were independent risk factors for treatment failure. The nomogram showed good discrimination [the area under the curve (AUC): 0.862], good calibration, and a net benefit in the range of probabilities between 5 and 90% according to the decision curve analysis. Conclusion: This study successfully established the nomogram prediction model based on three independent risk factors. Due to the high level of predicting accuracy, this nomogram could be a useful resource for pediatric orthopedic surgeons to identify patients at major risk of Pavlik harness failure who might need more reliable treatments.

6.
J Plant Physiol ; 279: 153828, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36252399

RESUMO

Anthocyanins can help plants adapt and resist adverse environments and have important nutritional and medicinal effects on human beings. However, how environmental factors affect the anthocyanins accumulation of plants and how to improve the anthocyanins content of plants in different soils needs further exploration. Hence, this study aimed to investigate the effects of environmental factors on the accumulation of cyanidin, petunidin, malvidin, and delphinidin in the fruits of Lycium ruthenicum in sandy desert grassland (SS), gravel desert grassland (GD), and saline-alkali desert grassland (SD) in the lower reaches of the Shiyang River Basin. The variable importance screened the key environmental factors affecting anthocyanin accumulation in projection (VIP) and multiple stepwise regressions. The structural equation model (SEM) was established to understand how the climate and soil factors affect the total anthocyanin accumulation. For establishing soil nutrient optimization schemes by partial least squares regression (PLS) and the simplex algorithm used to improve the anthocyanin content in different types of desert grassland. In SS, electrical conductivity (EC) and microbial biomass carbon (SMBC) showed highly significant and positive effects on the content of total anthocyanin, cyanidin, and petunidin. In GD, soil moisture and microbial biomass nitrogen (SNBN) significantly negatively affected total anthocyanin content. In SD, catalase (CAT), phosphatase (PHO), and total potassium (TK) had the greatest impact on total anthocyanin content. It is indicated that the targeted improvement measures are necessary to increase anthocyanin content in the fruit of Lycium ruthenicum.


Assuntos
Antocianinas , Lycium , Humanos , Antocianinas/química , Lycium/química , Frutas , Pradaria , Solo
7.
Oxid Med Cell Longev ; 2022: 2238985, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193080

RESUMO

Background: D-dimer (DD) has been indicated as a potential indicator due to its connection with the prognosis of the COVID-19 pandemic. Aging is linked to elevated DD levels in coagulation activation. However, few studies have investigated the correlation of DD with prognosis, especially in the old population. Therefore, this study aims at investigating the correlation of DD with prognosis in shock and perioperative populations over 65 years of age. Methods: We analyzed 9261 old patients admitted to intensive care units (ICUs) with either confirmed shock or in perioperative period of high-risk surgery, with 8813 of them had DD levels determined on admission. In-hospital mortality, length of ICU stay and ventilation time (VT) associated variables were assessed using generalized linear models. Results: Although DD levels had no positive correlations with in-hospital mortality (RR, 1.006; 95% CI, 0.998-1.014) and length of ICU stay (RR, 1.012; 95% CI, 0.997-1.028) in Model 3, they were strongly correlated with VT (RR, 1.577; 95% CI, 1.024-2.064). Higher DD levels in females (RR, 1.804; 95% CI, 1.116-2.602), those who used antibiotics (RR, 1.736; 95% CI, 1.092-2.453), those with surgery (RR, 1.640; 95% CI, 1.273-2.114), and those with shock (RR, 1.740; 95% CI, 1.001-2.687) had stronger correlation with longer VT than the counterparts. While patients who were between 65 and 74 years old (RR, 1.023; 95% CI, 1.003-1.043), with no use of antibiotics (RR, 1.007; 95% CI, 1.001-1.013) nor shock (RR, 1.011; 95% CI, 1.002-1.021), but had undergone surgical procedures (RR, 1.030; 95% CI, 1.012-1.048) were correlated with a longer ICU length of stay. Conclusion: DD levels at ICU admission are highly related to increased VT and length of ICU stay in the old population with either confirmed shock or after high-risk surgery, indicating the strong potential of DD as a marker with prognostic utility for all ICU patients in the future.


Assuntos
COVID-19 , Choque , Idoso , Antibacterianos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Pandemias , Estudos Retrospectivos
8.
Am J Transl Res ; 14(8): 5229-5242, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105025

RESUMO

Critical illness, particularly sepsis, is associated with high mortality, so prevention is more important than effective therapy. Advances in medical science have provided more opportunities for early warning and early intervention to avoid the development of critical illness. Existing early warning systems (EWS) have the advantages of high efficiency and convenience. However, with the development of medical technology, they do not completely meet clinical needs. EWS should contain elements that meet many dimensions of clinical requirements, including risk warning, response warning, injury warning, critical warning, and death warning. By summarizing previous studies, we outlined a layered EWS that follows RISK bundles. RISK represents different warning sign categories: R: host response, I: organ injury, S: changes in vital signs, and K: gradual appearance of "killed" organs. We plan to construct a complete layered EWS to guide clinical activities and subsequent clinical studies in the near future.

9.
Respir Res ; 23(1): 240, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096792

RESUMO

PURPOSE: To evaluate the prevalence, characteristics, and respiratory arousal threshold (ArTH) of Chinese patients with positional obstructive sleep apnea (POSA) according to the Cartwright Classification (CC) and Amsterdam Positional Obstructive Sleep Apnea Classification (APOC). METHODS: A large-scale cross-sectional study was conducted in our sleep center from 2007 to 2018 to analyze the clinical and polysomnography (PSG) data of Chinese POSA patients. Low ArTH was defined based on PSG indices. RESULTS: Of 5,748 OSA patients, 36.80% met the CC criteria, and 42.88% the APOC criteria, for POSA. The prevalence of POSA was significantly higher in women than men (40.21% and 46.52% vs. 36.13% and 42.18% for CC and APOC, respectively). Chinese POSA patients had a lower apnea hypopnea index (AHI) and lower oxygen desaturation index, shorter duration of oxygen saturation (SaO2) < 90%, and a higher mean SaO2 and higher lowest SaO2 value compared to subjects with non-positional OSA (NPOSA). More than 40% of the POSA patients had a low ArTH; the proportion was extremely high in the supine-isolated-POSA (si-POSA) group and APOC I group. In multivariate logistic regression analyses, higher mean SaO2 and lower AHI during sleep were positive predictors of POSA. CONCLUSIONS: According to the CC and APOC criteria, more than 1/3 of our Chinese subjects with OSA had POSA. Chinese POSA patients had less severe OSA and nocturnal hypoxia. Compared to NPOSA patients, significantly more patients with POSA had a low ArTH. A low ArTH may be an important endotype in the pathogenesis of POSA, especially in patients with si-POSA and APOC I. Further studies are necessary to develop personalized management strategies for POSA patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry; URL: http://www.chictr.org.cn ; No. ChiCTR1900025714 (retrospectively registered).


Assuntos
Postura , Apneia Obstrutiva do Sono , Apolipoproteínas C , Nível de Alerta , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Polissonografia , Prevalência , Sono , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Decúbito Dorsal
10.
J Immunotoxicol ; 19(1): 109-116, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36083248

RESUMO

The potential for effector functions of therapeutic antibodies, including antibody-dependent cell-mediated cytotoxicity (ADCC), is a biological activity of interest for characterization, regardless of if ADCC is an intended primary pharmacological effect. The composition of the conserved antibody Fc glycan can vary as a function of post-translational processing which may affect the binding affinity to Fc receptors, leading to a change of effector activity. Ordesekimab (AMG 714 or PRV-015), a fully human immunoglobulin G1-kappa anti-interleukin (IL)-15 monoclonal antibody, is in clinical development for celiac disease. The binding of ordesekimab to IL-15 inhibits the interaction of IL-15 with the IL-2Rß and common γ chain of the IL-15 receptor complex, but not with the IL-15Rα chain. Therefore, the simultaneous binding of ordesekimab to the Fcγ receptor (R) IIIα expressed on natural killer (NK) cells and to the IL-15/IL-15Rα complex on cells such as monocytes may theoretically enable ADCC toward the IL-15Rα-expressing cells. The high mannose (HM) levels on the Fc glycan were found to vary in different lots of ordesekimab resulting from refinements to the manufacturing process, and the impact on ordesekimab-mediated ADCC activity was evaluated in in vivo and in vitro studies. A review of nonclinical and clinical data found no evidence of ordesekimab-induced depletion of monocytes, or cytotoxicity in organs with wide IL-15Rα expression, suggesting a lack of in vivo ADCC activity. In addition, in vitro peripheral blood mononuclear cells-based ADCC assay did not reveal any cytolytic effect of ordesekimab with various levels of HM content when cocultured with recombinant human IL-15. Taken together, these data demonstrate that ADCC is not a potential liability for ordesekimab and does not contribute to the reduction of IL-15-mediated inflammation, the intended pharmacological effect.


Assuntos
Interleucina-15 , Leucócitos Mononucleares , Anticorpos Monoclonais Humanizados , Humanos , Interleucina-15/farmacologia , Polissacarídeos
11.
Comput Struct Biotechnol J ; 20: 5193-5202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059866

RESUMO

The coronavirus disease-2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seriously affected public health around the world. In-depth studies on the pathogenic mechanisms of SARS-CoV-2 is urgently necessary for pandemic prevention. However, most laboratory studies on SARS-CoV-2 have to be carried out in bio-safety level 3 (BSL-3) laboratories, greatly restricting the progress of relevant experiments. In this study, we used a bacterial artificial chromosome (BAC) method to assemble a SARS-CoV-2 replication and transcription system in Vero E6 cells without virion envelope formation, thus avoiding the risk of coronavirus exposure. Furthermore, an improved real-time quantitative reverse transcription PCR (RT-qPCR) approach was used to distinguish the replication of full-length replicon RNAs and transcription of subgenomic RNAs (sgRNAs). Using the SARS-CoV-2 replicon, we demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 facilitates the transcription of sgRNAs in the discontinuous synthesis process. Moreover, two high-frequency mutants of N protein, R203K and S194L, can obviously enhance the transcription level of the replicon, hinting that these mutations likely allow SARS-CoV-2 to spread and reproduce more quickly. In addition, remdesivir and chloroquine, two well-known drugs demonstrated to be effective against coronavirus in previous studies, also inhibited the transcription of our replicon, indicating the potential applications of this system in antiviral drug discovery. Overall, we developed a bio-safe and valuable replicon system of SARS-CoV-2 that is useful to study the mechanisms of viral RNA synthesis and has potential in novel antiviral drug screening.

12.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(8): 802-807, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36177921

RESUMO

OBJECTIVE: To explore the relationship between the pulse pressure/central venous pressure (PP/CVP) ratio and the cardiac output (CO) of patients after cardiac surgery from the basic principles of hemodynamics, and to further evaluate the predictive value of PP/CVP ratio in patients with secondary low cardiac output syndrome (LCOS) after cardiac surgery. METHODS: A retrospective study was conducted, and patients who received pulse indicator continuous cardiac output (PiCCO) monitoring were enrolled at the department of critical care medicine of Peking Union Medical College Hospital from January 1, 2016, to September 1, 2021. Patients were divided into two groups: the LCOS group [cardiac index (CI) < 33.34 mL×s-1×m-2, 25 cases] and the non-LCOS group (CI ≥ 33.34 mL×s-1×m-2, 125 cases) according to the CI at 6 hours after surgery. The general clinical data and hemodynamic parameters were collected. Correlations between PP/CVP ratio and PiCCO monitoring indicators were performed with Pearson or Spearman correlation test. Receiver operator characteristic curve (ROC curve) analysis was carried out to evaluate the predictive value of the parameters in patients with LCOS after cardiac surgery. RESULTS: A total of 150 patients with PiCCO monitoring after cardiac surgery were included. There were no differences in baseline characteristics between the two groups, while PP in the LCOS group was lower than that in the non-LCOS group [mmHg (1 mmHg ≈ 0.133 kPa): 40 (37, 44) vs. 55 (46, 64)], CVP was higher than that in the non-LCOS group [mmHg: 12 (11, 14) vs. 10 (8, 12)], and PP/CVP ratio in the LCOS group was lower than that in the non-LCOS group [3.3 (2.9, 3.7) vs. 5.5 (4.6, 6.8)], with significant differences (all P < 0.05). Correlation analysis results showed that PP/CVP ratio was positively correlated with CI, CO, and stroke volume index (SVI), respectively (rs = 0.660, 0.592, 0.600, all P < 0.001). CI was negatively correlated with PP (rs = 0.509, P < 0.001) and positively correlated with CVP (rs = -0.297, P < 0.001). ROC curve analysis revealed that compared with PP, CVP, SVI and cardiac function index (CFI), PP/CVP ratio was the best predictor of LCOS after cardiac surgery [area under the ROC curve (AUC) was 0.94±0.02, P < 0.001], when the optimum cut-off value was 4.41, the sensitivity was 80.00%, and the specificity was 96.00%. CONCLUSIONS: PP/CVP ratio was moderately positively correlated with CO after cardiac surgery, and PP/CVP ratio could be used as a prognostic predictor for LCOS after cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Choque Séptico , Pressão Sanguínea , Débito Cardíaco , Baixo Débito Cardíaco , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pressão Venosa Central , Hemodinâmica , Humanos , Estudos Prospectivos , Estudos Retrospectivos
13.
Front Public Health ; 10: 944605, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159233

RESUMO

This research aims to explore the influence of seamless nursing mode of humanistic care on nursing quality and blood infection risk of ICU patients in neurosurgery, and the model of correlation with APACHE II score. 110 ICU patients are grouped into control set and study set, which are, respectively, given the previous routine nursing and the seamless management based on humanistic care to compare the two sets in the following aspects: nursing quality, blood infection rate, anxiety and depression extension before and after nursing, nursing satisfaction and APACHE II score, and to figure out the correlation between patient nursing quality score, and to compare blood infection and APACHE II score. Comparison and statistical analysis are used to disclose the influence and the correlation. The results show that there is not only a large negative correlation between nursing quality scores and APACHE II scores, but also a large negative correlation between the risk of blood infection and APACHE II score.


Assuntos
Unidades de Terapia Intensiva , Modelos de Enfermagem , APACHE , Humanos
14.
Hepatol Int ; 16(5): 1179-1187, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36001228

RESUMO

PURPOSE: Stereotactic body radiotherapy (SBRT) may have significant immunomodulatory effects that enhance tumor response to immune checkpoint inhibitors. This phase 2 clinical trial was conducted to evaluate the safety and efficacy of combining palliative SBRT with camrelizumab (an anti-PD1 monoclonal antibody) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Patients with uHCC, Child-Pugh A/B liver function, and at least one measurable lesion were enrolled between April 2020 and August 2022. Patients were administered 200 mg camrelizumab intravenously from the first day of palliative SBRT and then every 3 weeks. Palliative SBRT was delivered daily over five fractions per week, with a dose range of 30-50 Gy. The primary endpoints were objective response rate (ORR) and safety. This trial was registered at ClinicalTrials.gov (NCT04193696). RESULTS: Twenty-one patients were enrolled; the median radiation dose was 40 Gy, and the median number of cycles of camrelizumab was five. The ORR was 52.4%. After a median follow-up of 19.7 months, the median progression-free and overall survival were 5.8 and 14.2 months, respectively. The overall survival probability was 85.7% at 6 months, 76.2% at 9 months, and 59.9% at 12 months. All grade 3 treatment-related adverse events (TRAEs) occurred in five patients (23.8%) and were manageable. No grade 4/5 TRAEs were observed. CONCLUSION: Palliative SBRT plus camrelizumab showed promising antitumor activity against uHCC. Toxicities were manageable with no unexpected safety issues. This study provides evidence of a new therapeutic method for the treatment of uHCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Radiocirurgia/métodos
15.
ALTEX ; 2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-36044561

RESUMO

Immune responses are heavily involved in the regulation and pathogenesis of human diseases, including infectious diseases, inflammatory and autoimmune conditions, cancer, neurological disorders and cardiometabolic syndromes. The immune system has been considered as a double-edged sword serving as a powerful host defense mechanism against infection and cancerous cells and causing detrimental tissue damage when the immune response is exaggerated or uncontrollable. One of the challenges in studying the efficacy and toxicity of drugs that target or modulate the immune system is the lack of suitable preclinical human models that are predictive of human response. Recent advancements in human microphysiological systems (MPS) have provided a promising in vitro platform to evaluate the response of immune organs ex vivo, to investigate the interaction of immune cells with non-lymphoid tissue cells, and to reduce the reliance on animals in preclinical studies. The development, regulation, trafficking, and responses of immune cells have been extensively studied in preclinical animal models and clinically, providing a wealth of knowledge by which to evaluate new in vitro models. Therefore, the application of immunocompetent MPS in drug discovery and development should first verify that the immune response in an MPS model recapitulates complexity of the human immune physiology. This manuscript reviews biological functions of immune organ systems and tissue-resident immune cells and discusses contexts-of-use for commonly used immunocompetent and immune organ MPS models. Current perspective and recommendations are provided to guide the continued development of immune organ and immunocompetent MPS models and their application in drug discovery and development.

16.
Environ Res ; 215(Pt 1): 114127, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36041541

RESUMO

Understanding the relationship between precipitation and SARS-CoV-2 is significant for combating COVID-19 in the wet season. However, the causes for the variation of SARS-CoV-2 transmission intensity after precipitation is unclear. Starting from "the Zhengzhou event," we found that the virus-laden standing water formed after precipitation might trigger some additional routes for SARS-CoV-2 transmission and thus change the transmission intensity of SARS-CoV-2. Then, we developed an interdisciplinary framework to examine whether the health risk related to the virus-laden standing water needs to be a concern. The framework enables the comparison of the instant and lag effects of precipitation on the transmission intensity of SARS-CoV-2 between city clusters with different formation risks of the virus-laden standing water. Based on the city-level data of China between January 01, 2020, and December 31, 2021, we conducted an empirical study. The result showed that in the cities with a high formation risk of the virus-laden standing water, heavy rain increased the instant transmission intensity of SARS-CoV-2 by 6.2% (95%CI: 4.85-10.2%), while in the other cities, precipitation was uninfluential to SARS-CoV-2 transmission, revealing that the health risk of the virus-laden standing water should not be underestimated during the COVID-19 pandemic. To reduce the relevant risk, virus-laden water control and proper disinfection are feasible response strategies.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Óxido de Deutério , Humanos , Pandemias , Água
17.
Front Med (Lausanne) ; 9: 938536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966841

RESUMO

Background: Sepsis-induced cardiomyopathy significantly increased the mortality of patients with sepsis. The diagnostic criteria for septic cardiomyopathy has not been unified, which brings serious difficulties to clinical treatment. This study aimed to provide evidence for the early identification and intervention in patients with sepsis by clarifying the relationship between the ultrasound phenotype of septic cardiomyopathy and the prognosis of patients with sepsis. Methods: This was a multicenter, prospective cohort study. The study population will consist of all eligible consecutive patients with sepsis or septic shock who meet the Sepsis 3.0 diagnostic criteria and were aged ≥18 years. Clinical data and echocardiographic measurements will be recorded within 2 h, at the 24th hour, at the 72nd hour, and on the 7th day after admission. The prevalence of each phenotype will be described as well, and their association with prognosis will be analyzed statistically. Discussion: To achieve early recognition, prevent reinjury, achieve precise treatment, and reduce mortality in patients with sepsis, it is important to identify septic cardiac alterations and classify the phenotypes at all stages of sepsis. First, there is a lack of studies on the prevalence of each phenotype in Chinese populations. Second, each phenotype and its corresponding prognosis are not clear. In addition, the prognosis of patients with normal cardiac ultrasound phenotypes vs. those with suppressed or hyperdynamic cardiac phenotypes is unclear. Finally, this study was designed to collect data at four specific timing, then the timing of occurrence, duration, changes over time, impact to outcomes of each phenotype will probably be found. This study is expected to establish a standard and objective method to assess the ultrasound phenotype of septic cardiomyopathy due to its advantages of visualization, non-invasiveness and reproducibility, and to provide more precise information for the hemodynamic management of septic patients. In addition, this research will promote the clinical application of critical care ultrasound, which will play an important role in medical education and make ultrasound the best method to assess cardiac changes in sepsis. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05161104, identifier NCT05161104.

18.
Int J Mol Sci ; 23(16)2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-36012333

RESUMO

Nitrate is the preferred nitrogen source for plants and plays an important role in plant growth and development. Under various soil stresses, plants reallocate nitrate to roots to promote stress tolerance through the ethylene-ethylene response factors (ERFs)-nitrate transporter (NRT) signaling module. As a light signal, ultraviolet B (UV-B) also stimulates the production of ethylene. However, whether UV-B regulates nitrate reallocation in plants via ethylene remains unknown. Here, we found that UV-B-induced expression of ERF1B, ORA59, ERF104, and NRT1.8 in both Arabidopsis shoots and roots as well as nitrate reallocation from hypocotyls to leaves and roots were impaired in ethylene signaling mutants for Ethylene Insensitive2 (EIN2) and EIN3. UV-B-induced NRT1.8 expression and nitrate reallocation to leaves and roots were also inhibited in the triple mutants for ERF1B, ORA59, and ERF104. Deletion of NRT1.8 impaired UV-B-induced nitrate reallocation to both leaves and roots. Furthermore, UV-B promoted ethylene release in both shoots and roots by enhancing the gene expression and enzymatic activities of ethylene biosynthetic enzymes only in shoots. These results show that ethylene acts as a local and systemic signal to mediate UV-B-induced nitrate reallocation from Arabidopsis hypocotyls to both leaves and roots via regulating the gene expression of the ERFs-NRT1.8 signaling module.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Transporte de Ânions/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Etilenos/metabolismo , Fator VIII/genética , Regulação da Expressão Gênica de Plantas , Mutação , Nitratos/metabolismo , Óxidos de Nitrogênio/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo
19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(2): 102-107, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-36031565

RESUMO

Objective: To investigate the liver injury induced by lung ischemia / reperfusion(LI/R) and the role of autophagy in its prevention and treatment. Methods: The lung ischemia/reperfusion injury(LI/RI) model was prepared by anesthetizing the rats, cutting the trachea for mechanical ventilation, and using an arterial clamp to close the pulmonary hilum to simulate the ischemic process, and releasing the arterial clamp after 30 min to resume perfusion for 3 h. SD rats(n=24)were randomly divided into sham operation(sham)group,ischemia/reperfusion(I/R)group,solvent(DMSO)group and autophagy inhibitor (3-MA) group, 6 rats in each group. The rats were intraperitoneally injected with medicine before operation. After the rat LI/RI model was established,the rats were killed, and the lung wet/dry weight ratio was used to evaluate the success of modeling, the venous blood was collected to measure the contents of ALT and AST, and the liver tissues were collected. Light and electron microscopes were used to observed the liver tissues and cell shapes. The protein and mRNA expression levels of autophagy related proteins were determined by Western blot and RT-qPCR to suggest autophagy levels. Results: Compared with sham group, the lung wet/dry weight ratios in other groups were elevated, and the liver tissues of other groups were damaged significantly. Serum levels of AST and ALT were increased significantly and liver tissue damage was obvious, especially in I/R group. The light microscopy showed that the arrangement of hepatic cords was disordered or broken, hepatic sinuses were dilated, and edema of liver cells were observed; transmission electron microscopy showed varying degrees of mitochondria swelling up in liver cells in the other groups. At the same time, the expressions of AMPK, Beclin 1 and LC3 mRNA were increased, but the expressions of mTOR and p62 mRNA were decreased; the protein expressions of p-AMPK, Beclin 1, LC3-B were increased significantly, but those of p-mTOR and p62 were decreased (all P<0.05). Compared with DMSO group, the injury of liver tissue in 3-MA group was alleviated, the damage degree of mitochondrial ultrastructure was lower, the levels of AST and ALT were decreased, the transcription and protein expression levels of autophagy related protein in liver tissue were decreased (P<0.05). However, the injury degree of IR and DMSO groups were similar, and there was no significant differences in each index (P>0.05). Conclusion: Lung ischemia/reperfusion can cause liver injury in rats. Autophagy can mediate liver injury induced by lung ischemia / reperfusion in rats and inhibiting autophagy can effectively reduce liver injury induced by LI/R in rats.


Assuntos
Proteínas Quinases Ativadas por AMP , Traumatismo por Reperfusão , Animais , Autofagia , Proteína Beclina-1 , Dimetil Sulfóxido , Isquemia , Fígado , Pulmão , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Reperfusão , Serina-Treonina Quinases TOR
20.
AAPS PharmSciTech ; 23(6): 193, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35821540

RESUMO

This study aimed to prepare effervescent tablets of traditional Chinese medicine Xianganfang with fresh juice using a semi-solid 3D printer with three cartridge holders to seperate acid and alkali source by drug paste through model design to avoid sticking impact and premature effervescence during the tableting in the conventional preparation process. The powder of Xianganfang including fresh juice of Phyllanthus emblica and licorice extract was obtained by vacuum freeze-drying with 50% mannitol as cryoprotectant. Then, the formulation of 3D-printed effervescent tablets was investigated. Further 5% HPMC hydroalcoholic gel was mixed with sodium bicarbonate and freeze-dried Xianganfang powder to prepare alkali source and drug paste respectively while 30% PVP ethanol solution was mixed with tartaric acid to prepare acid source paste; these three pastes had good printability. The pastes of drug, acid, and alkali were loaded into three syringe cartridges separately and numbered as "3," "5," and "7," according to cartridge holders of the 3D printer, and printed in the order of "537,353,735" for separating acid and alkali by drug to avoid premature effervescence. And the basic printing parameters were optimized. The tablets were evaluated by the appearance, tablet weight variation, hardness, disintegration time, friability, pH, and stability. The physicochemical properties all conformed to the Chinese Pharmacopoeia 2020 edition. The content of the active ingredient gallic acid was 0.769 ± 0.019 mg/g. This study provided a new method to prepare effervescent tablets of traditional Chinese medicine with fresh juice using 3D printing technology.


Assuntos
Excipientes , Tecnologia Farmacêutica , Álcalis , Liberação Controlada de Fármacos , Excipientes/química , Pós , Comprimidos/química , Tecnologia Farmacêutica/métodos
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