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1.
Clin Nutr ESPEN ; 61: 28-36, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38777444

RESUMEN

Shock is a common critical illness characterized by microcirculatory disorders and insufficient tissue perfusion. Patients with shock and hemodynamic instability generally require vasopressors to maintain the target mean arterial pressure. Enteral nutrition (EN) is an important therapeutic intervention in critically ill patients and has unique benefits for intestinal recovery. However, the initiation of early EN in patients with shock receiving vasopressors remains controversial. Current guidelines make conservative and vague recommendations regarding early EN support in patients with shock. Increasing studies demonstrates that early EN delivery is safe and feasible in patients with shock receiving vasopressors; however, this evidence is based on observational studies. Changes in gastrointestinal blood flow vary by vasopressor and inotrope and are complex. The risk of gastrointestinal complications, especially the life-threatening complications of non-occlusive mesenteric ischemia and non-occlusive bowel necrosis, cannot be ignored in patients with shock during early EN support. It remains a therapeutic challenge in critical care nutrition therapy to determine the initiation time of EN in patients with shock receiving vasopressors and the safe threshold region for initiating EN with vasopressors. Therefore, the current review aimed to summarize the evidence on the optimal and safe timing of early EN initiation in patients with shock receiving vasopressors to improve clinical practice.


Asunto(s)
Enfermedad Crítica , Nutrición Enteral , Choque , Vasoconstrictores , Humanos , Vasoconstrictores/uso terapéutico , Vasoconstrictores/administración & dosificación , Nutrición Enteral/métodos , Choque/terapia , Enfermedad Crítica/terapia , Cuidados Críticos/métodos , Factores de Tiempo
2.
Front Public Health ; 12: 1349753, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38699425

RESUMEN

Background: An increase in Heatstroke cases occurred in southwest China in 2022 due to factors like global warming, abnormal temperature rise, insufficient power supply, and other contributing factors. This resulted in a notable rise in Heatstroke patients experiencing varying degrees of organ dysfunction. This descriptive study aims to analyze the epidemiology and clinical outcomes of Heatstroke patients in the ICU, providing support for standardized diagnosis and treatment, ultimately enhancing the prognosis of Heatstroke. Methods: A retrospective, multicenter, descriptive analysis was conducted on Heatstroke patients admitted to ICUs across 83 hospitals in southwest China. Electronic medical records were utilized for data collection, encompassing various aspects such as epidemiological factors, onset symptoms, complications, laboratory data, concurrent infections, treatments, and patient outcomes. Results: The dataset primarily comprised classic heatstroke, with 477 males (55% of total). The patient population had a median age of 72 years (range: 63-80 years). The most common initial symptoms were fever, mental or behavioral abnormalities, and fainting. ICU treatment involved respiratory support, antibiotics, sedatives, and other interventions. Among the 700 ICU admissions, 213 patients had no infection, while 487 were diagnosed with infection, predominantly lower respiratory tract infection. Patients presenting with neurological symptoms initially (n = 715) exhibited higher ICU mortality risk compared to those without neurological symptoms (n = 104), with an odds ratio of 2.382 (95% CI 1.665, 4.870) (p = 0.017). Conclusion: In 2022, the majority of Heatstroke patients in southwest China experienced classical Heatstroke, with many acquiring infections upon admission to the ICU. Moreover, Heatstroke can result in diverse complications.


Asunto(s)
Golpe de Calor , Unidades de Cuidados Intensivos , Humanos , Golpe de Calor/epidemiología , Golpe de Calor/mortalidad , Masculino , China/epidemiología , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Unidades de Cuidados Intensivos/estadística & datos numéricos , Factores de Riesgo
4.
Front Pharmacol ; 15: 1378090, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633610

RESUMEN

Objective: The aim of this study was to investigate the potential risk of drug-induced liver injury (DILI) caused by the CDK4/6 inhibitors (CDK4/6is abemaciclib, ribociclib, and palbociclib by comprehensively analyzing the FDA Adverse Event Reporting System (FAERS) database. Moreover, potential toxicological mechanisms of CDK4/6is-related liver injury were explored via drug-gene network analysis. Methods: In this retrospective observational study, we collected reports of DILI associated with CDK4/6i use from the FAERS dated January 2014 to March 2023. We conducted disproportionality analyses using the reporting odds ratio (ROR) with a 95% confidence interval (CI). Pathway enrichment analysis and drug-gene network analyses were subsequently performed to determine the potential mechanisms underlying CDK4/6i-induced liver injury. Results: We found positive signals for DILI with ribociclib (ROR = 2.60) and abemaciclib (ROR = 2.37). DILIs associated with liver-related investigations, signs, and symptoms were confirmed in all three reports of CDK4/6is. Moreover, ascites was identified as an unlisted hepatic adverse effect of palbociclib. We isolated 189 interactive target genes linking CDK4/6 inhibitors to hepatic injury. Several key genes, such as STAT3, HSP90AA1, and EP300, were revealed via protein-protein analysis, emphasizing their central roles within the network. KEGG pathway enrichment of these genes highlighted multiple pathways. Conclusion: Our study revealed variations in hepatobiliary toxicity among the different CDK4/6 inhibitors, with ribociclib showing the highest risk of liver injury, followed by abemaciclib, while palbociclib appeared relatively safe. Our findings emphasize the need for cautious use of CDK4/6 inhibitors, and regular liver function monitoring is recommended for long-term CDK4/6 inhibitor use.

5.
Sci Adv ; 10(14): eadj9305, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38569042

RESUMEN

The power and scope of disease modeling can be markedly enhanced through the incorporation of broad genetic diversity. The introduction of pathogenic mutations into a single inbred mouse strain sometimes fails to mimic human disease. We describe a cross-species precision disease modeling platform that exploits mouse genetic diversity to bridge cell-based modeling with whole organism analysis. We developed a universal protocol that permitted robust and reproducible neural differentiation of genetically diverse human and mouse pluripotent stem cell lines and then carried out a proof-of-concept study of the neurodevelopmental gene DYRK1A. Results in vitro reliably predicted the effects of genetic background on Dyrk1a loss-of-function phenotypes in vivo. Transcriptomic comparison of responsive and unresponsive strains identified molecular pathways conferring sensitivity or resilience to Dyrk1a1A loss and highlighted differential messenger RNA isoform usage as an important determinant of response. This cross-species strategy provides a powerful tool in the functional analysis of candidate disease variants identified through human genetic studies.


Asunto(s)
Células Madre Pluripotentes , Animales , Ratones , Humanos , Fenotipo
7.
Artículo en Inglés | MEDLINE | ID: mdl-38483719

RESUMEN

Automated guided vehicles (AGVs) are typical intelligent logistics equipment, and path planning plays a significant role in the efficient use of AGVs. To better utilize multi-load AGVs and enhance the sustainability of the logistics process, an energy-efficient path planning model is formulated for a multi-load AGV executing multiple transport tasks in a manufacturing workshop environment, with transport distance and energy consumption (EC) serving as optimization objectives. Furthermore, a two-stage approach is proposed to solve it. In the first stage, the optimal energy-efficient paths connecting any two different nodes are acquired based on the workshop transport network expressed as a topological map. Afterward, the non-dominated sorting genetic algorithm-II is adopted in the second stage to determine the optimal execution sequence of pickup and delivery operations related to the assigned transport tasks, as well as to select the optimal path from the first stage's output information to execute each operation simultaneously. Moreover, the experimental study validates the energy-saving effect of the established model and the effectiveness of the solution method, and the factors affecting the multi-load AGV EC are analyzed.

8.
J Neurosci ; 44(18)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38508714

RESUMEN

Drugs of abuse induce neuroadaptations, including synaptic plasticity, that are critical for transition to addiction, and genes and pathways that regulate these neuroadaptations are potential therapeutic targets. Tropomodulin 2 (Tmod2) is an actin-regulating gene that plays an important role in synapse maturation and dendritic arborization and has been implicated in substance abuse and intellectual disability in humans. Here, we mine the KOMP2 data and find that Tmod2 knock-out mice show emotionality phenotypes that are predictive of addiction vulnerability. Detailed addiction phenotyping shows that Tmod2 deletion does not affect the acute locomotor response to cocaine administration. However, sensitized locomotor responses are highly attenuated in these knock-outs, indicating perturbed drug-induced plasticity. In addition, Tmod2 mutant animals do not self-administer cocaine indicating lack of hedonic responses to cocaine. Whole-brain MR imaging shows differences in brain volume across multiple regions, although transcriptomic experiments did not reveal perturbations in gene coexpression networks. Detailed electrophysiological characterization of Tmod2 KO neurons showed increased spontaneous firing rate of early postnatal and adult cortical and striatal neurons. Cocaine-induced synaptic plasticity that is critical for sensitization is either missing or reciprocal in Tmod2 KO nucleus accumbens shell medium spiny neurons, providing a mechanistic explanation of the cocaine response phenotypes. Combined, these data, collected from both males and females, provide compelling evidence that Tmod2 is a major regulator of plasticity in the mesolimbic system and regulates the reinforcing and addictive properties of cocaine.


Asunto(s)
Cocaína , Cuerpo Estriado , Ratones Noqueados , Plasticidad Neuronal , Animales , Cocaína/farmacología , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Ratones , Masculino , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Ratones Endogámicos C57BL , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiología , Femenino , Trastornos Relacionados con Cocaína/fisiopatología , Trastornos Relacionados con Cocaína/genética , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genética , Excitabilidad Cortical/efectos de los fármacos , Inhibidores de Captación de Dopamina/farmacología , Inhibidores de Captación de Dopamina/administración & dosificación
9.
World J Gastroenterol ; 30(4): 346-366, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38313238

RESUMEN

BACKGROUND: Extreme heat exposure is a growing health problem, and the effects of heat on the gastrointestinal (GI) tract is unknown. This study aimed to assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. AIM: To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. METHODS: Patients admitted to the intensive care unit (ICU) due to heatstroke were included from 83 centres. Patient history, laboratory results, and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15, ICU discharge, or death. GI symptoms, including nausea/vomiting, diarrhoea, flatulence, and bloody stools, were recorded. The characteristics of patients with heatstroke concomitant with GI symptoms were described. Multivariable regression analyses were performed to determine significant predictors of GI symptoms. RESULTS: A total of 713 patients were included in the final analysis, of whom 132 (18.5%) patients had at least one GI symptom during their ICU stay, while 26 (3.6%) suffered from more than one symptom. Patients with GI symptoms had a significantly higher ICU stay compared with those without. The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom. Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms. CONCLUSION: The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.


Asunto(s)
Enfermedades Gastrointestinales , Golpe de Calor , Humanos , Estudios Retrospectivos , Enfermedad Crítica , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/etiología , Unidades de Cuidados Intensivos , Golpe de Calor/complicaciones , Golpe de Calor/epidemiología
10.
Skin Res Technol ; 30(2): e13626, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38385847

RESUMEN

BACKGROUND: The complex network connections, information transmission and organization play key roles in brain cognition on sensory stimulation. Previous studies showed that several brain regions of somatosensory, motor, emotional, cognitive, etc. are linked to fabric-evoked prickle. But the functional connectivity characteristics of the brain network involved in prickle perception is still unclear. MATERIALS AND METHODS: In the present study, resting state fMRI (functional magnetic resonance imaging) with functional connectivity analysis was adopted to build the initial brain functional network, and task fMRI with psychophysiological interaction analysis was employed to investigate modulation features of prickling task to functional connections in the brain network. RESULTS: The results showed that, in resting state, six groups or sub-networks can be identified in the prickle network, and when the subjects performed the prickling task, functional connectivity strength between some seed regions (e.g., somatosensory regions and precuneus, emotional regions and the prefrontal cortex, etc.) in the network increased. CONCLUSION: Combining resting-state fMRI with task fMRI is a feasible and promising method to study functional connectivity characteristics of the brain network involved in prickle perception. It is inferred that the "itch" ingredient of prickle sensation was transmitted from somatosensory cortices to precuneus, and emotional attribute (e.g., pain) from somatosensory cortices to the prefrontal cortex and at last to emotional regions.


Asunto(s)
Encéfalo , Emociones , Humanos , Encéfalo/diagnóstico por imagen , Cognición , Dolor , Percepción
11.
Int J Endocrinol ; 2024: 4002839, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410172

RESUMEN

Background: The association between atherogenic index of plasma (AIP) and hyperuricemia remains indistinct. This study was aimed to examine the relationship between AIP and hyperuricemia among the middle-aged and the elderly Chinese population. Methods: Datasets were retrieved from the China Health and Retirement Longitudinal Study (CHARLS) survey conducted in 2011 and 2015. 13,021 participants in the CHARLS in 2011 and 7,017 participants involved both in 2011 and 2015 were included, respectively. The measurement of AIP and hyperuricemia was based on the test of fasting blood. Association between AIP and hyperuricemia was assessed by logistic regression, and the nonlinear association was examined by restricted cubic splines (RCS). The cutoff point of AIP was calculated using receiver operator curve (ROC). 1 : 1 propensity score matching (PSM) was adopted to further explore the relationship between AIP and hyperuricemia. Results: In the section of a cross-sectional study, a positive association between AIP and hyperuricemia was found. The odds ratios (ORs) of hyperuricemia were 1.00 (reference), 1.52 (1.10-2.10), 1.80 (1.31-2.47), and 3.81 (2.84-5.11). Nonlinear association was not detected using RCS analysis. There were 664 hyperuricemia cases during the four years follow-up. The hyperuricemia prevalence was 9.5%. In the fully adjusted longitudinal analysis, the ORs for hyperuricemia across the quartiles of AIP were 1.00 (reference), 1.00 (0.74-1.37), 1.59 (1.20-2.11), and 2.55 (1.94-3.35), respectively. In the longitudinal analysis after PSM, the OR of hyperuricemia were 1.91 (1.45, 2.51) and 1.92 (1.45, 2.54) in the univariate and multivariate model, respectively. Conclusion: AIP can predict the prevalence of hyperuricemia in the Chinese middle-aged and elderly population.

12.
J Thorac Dis ; 16(1): 516-529, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38410549

RESUMEN

Background: Red blood cell (RBC) distribution width (RDW) to albumin ratio is a novel biomarker and its prognostic effect on critically ill patients with sepsis has not been extensively investigated. The objective of this study was to identify the prognostic value of the RDW to albumin ratio in these patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. A Cox proportional hazards model and restricted cubic spline model were used to determine the association of RDW to albumin ratio with mortality. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were applied, and the area under the curve (AUC) was used to compare the predictive value. Results: A total of 3,969 eligible patients were enrolled. The median RDW to albumin ratio was significantly higher in non-survivors than in survivors at 30 and 90 days. Patients were divided into groups according to the RDW to albumin ratio, and the risk of 30- and 90-day mortality markedly increased in the group with a higher ratio. The relationship between the RDW to albumin ratio as a continuous variable and 30-day mortality also showed an upward trend in the restricted cubic spline. The AUC of the RDW to albumin ratio was 0.633 in discriminating 30-day mortality which was similar to that of the lactate to albumin ratio (AUC =0.617; P=0.133) and higher than that of the neutrophil percentage to albumin ratio (AUC =0.559; P<0.001). Conclusions: The RDW to albumin ratio is a promising biomarker for assessing the prognosis of critically ill patients with sepsis. Its predictive value in determining mortality was found to be similar to that of the lactate to albumin ratio and superior to that of the neutrophil percentage to albumin ratio.

13.
Clin Exp Med ; 24(1): 31, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300370

RESUMEN

At present, although there are tumor markers for hepatocellular carcinoma (HCC), markers with better predictive efficiency are needed. SAA4 gene expression in liver tumor and paracancerous tissues was analyzed using The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were analyzed and visualized by heatmap and volcano plot. Survival analysis was performed based on SAA4 expression. SAA4 expression was compared in patients grouped based on clinicopathological features, and gene set enrichment analysis (GSEA) was conducted. Immunohistochemical staining was used to verify the SAA4 protein staining intensity from The Human Protein Atlas database and our center's samples. The diagnostic value of SAA4 for HCC was evaluated by receiver operating characteristic curves. SAA4 was expressed at low levels in HCC tissues, and low SAA4 expression was associated with a poor prognosis in HCC. In addition, SAA4 expression decreased with HCC progression. There were 188 upregulated DEGs and 1551 downregulated DEGs between the high and low SAA4 expression groups. Complement and coagulation cascades, fatty acid metabolism, and ECM receptor interaction were significantly enriched in the GSEA. SAA4 had good predictive efficacy for HCC and even early HCC and was superior to AFP. In general, low SAA4 expression was associated with advanced HCC stage and a poor prognosis. In addition, SAA4 may be helpful for the diagnosis of early HCC and may become a novel tumor marker with good predictive power for HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Biomarcadores de Tumor/genética , Expresión Génica , Pronóstico , Proteína Amiloide A Sérica/genética
14.
Ther Clin Risk Manag ; 20: 47-58, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38344194

RESUMEN

Objective: The objective of this study was to utilize LASSO regression (Least Absolute Shrinkage and Selection Operator Regression) to identify key variables in septic patients and develop a predictive model for intensive care unit (ICU) mortality. Methods: We conducted a cohort consisting of septic patients admitted to the ICU between December 2016 and July 2019. The disease severity and laboratory index were analyzed using LASSO regression. The selected variables were then used to develop a model for predicting ICU mortality. AUCs of ROCs were applied to assess the prediction model, and the accuracy, sensitivity and specificity were calculated. Calibration were also used to assess the actual and predicted values of the predictive model. Results: A total of 1733 septic patients were included, among of whom 382 (22%) died during ICU stay. Ten variables, namely mechanical ventilation (MV) requirement, hemofiltration (HF) requirement, norepinephrine (NE) requirement, septicemia, multiple drug-resistance infection (MDR), thrombocytopenia, hematocrit, red-cell deviation width coefficient of variation (RDW-CV), C-reactive protein (CRP), and antithrombin (AT) III, showed the strongest association with sepsis-related mortality according to LASSO regression. When these variables were combined into a predictive model, the area under the curve (AUC) was found to be 0.801. The AUC of the validation group was 0.791. The specificity of the model was as high as 0.953. Within the probability range of 0.25 to 0.90, the predictive performance of the model surpassed that of individual predictors within the cohort. Conclusion: Our findings suggest that a predictive model incorporating the variables of MV requirement, HF requirement, NE requirement, septicemia, MDR, thrombocytopenia, HCT, RDW-CV, CRP, and AT III exhibiting an 80% likelihood of predicting ICU mortality in sepsis and demonstrates high accuracy.

15.
Foods ; 13(4)2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38397535

RESUMEN

Starchy foods are an essential part of people's daily diet. Starch is the primary substance used by plants to store carbohydrates, and it is the primary source of energy for humans and animals. In China, a variety of plants, including edible medicinal plants, such as Pueraria root, yam tuber and coix seed, are rich in starch. However, limited by their inherent properties, kudzu starch and other starches are not suitable for the modern food industry. Natural starch is frequently altered by physical, chemical, or biological means to give it superior qualities to natural starch as it frequently cannot satisfy the demands of industrial manufacturing. Therefore, the deep processing market of modified starch and its products has a great potential. This paper reviews the modification methods which can provide excellent functional, rheological, and processing characteristics for these starches that can be used to improve the physical and chemical properties, texture properties, and edible qualities. This will provide a comprehensive reference for the modification and application of starch from medicinal and edible plants.

16.
Semin Immunopathol ; 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38170255

RESUMEN

Glycoprotein 2 (GP2) is a widely distributed protein in the digestive tract, contributing to mucosal barrier maintenance, immune homeostasis, and antigen-specific immune response, while also being linked to inflammatory bowel disease (IBD) pathogenesis. This review sheds light on the extensive distribution of GP2 within the gastrointestinal tract and its intricate interplay with the immune system. Furthermore, the significance of GP2 autoantibodies in diagnosing and categorizing IBD is underscored, alongside the promising therapeutic avenues for modulating GP2 to regulate immunity and maintain mucosal balance.

17.
BMC Infect Dis ; 24(1): 149, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38291390

RESUMEN

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis. METHODS: Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared. RESULTS: A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226-6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS. CONCLUSIONS: SIRS is highly frequent in patients with SFTS, and it is associated with high mortality.


Asunto(s)
Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Trombocitopenia , Humanos , Estudios Retrospectivos , Prevalencia , Trombocitopenia/complicaciones , Fiebre/epidemiología , Pronóstico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , China/epidemiología
18.
Vaccine ; 42(6): 1259-1267, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38281898

RESUMEN

Coronavirus Disease 2019 (COVID-19) vaccines protect the public and limit viral spread. However, inactivated viral vaccines use the whole virus particle, which contains many non-capsid proteins that may cause adverse immune responses. A report has found that the ADP-ribose-binding domains of SARS-CoV-2 non-structural protein 3 (NSP3) and human poly(ADP-ribose) polymerase family member 14 (PARP14) share a significant degree of homology. Here, we further show that antibodies against 2019 novel SARS-like coronavirus (SARS-CoV-2) NSP3 can bind human PARP14 protein. However, when G159R + G162R mutations were introduced into NSP3, the antibody titer against human PARP14 decreased 14-fold. Antibodies against SARS-CoV-2 NSP3 can cross-react with human skeletal muscle cells and astrocytes, but not human embryonic kidney 293T cells. However, when G159R + G162R mutations were introduced into NSP3, the cross-reaction was largely inhibited. The results imply that COVID-19 patients with high antibody titers against NSP3 may have high risks of muscular and/or neurological complications. And the possible strategies to improve the safety of inactivated viral vaccines are also discussed.


Asunto(s)
COVID-19 , Vacunas Virales , Humanos , SARS-CoV-2/genética , Proteínas no Estructurales Virales/química , Vacunas contra la COVID-19 , Anticuerpos , Células Musculares/metabolismo , Neuroglía/metabolismo
19.
Biochem Pharmacol ; 220: 115980, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38081368

RESUMEN

Smoking is a documented risk factor for cancer, e.g., gastric cancer. Nicotine, the principal tobacco alkaloid, would exert its role of contribution to gastric cancer development and progression through nicotinic acetylcholine receptors (nAChRs) and ß-adrenergic receptors (ß-ARs), which then promote cancer cell proliferation, migration and invasion. As a key isoenzyme in conversion of arachidonic acid to prostaglandins, cyclooxygenase-2 (COX-2) has been demonstrated to have a wide range of effects in carcinogenesis and tumor development. At present, many studies have reported the effect of nicotine on gastric cancer by binding to nAChR, as well as indirectly stimulating ß-AR to mediate COX-2-related pathways. This review summarizes these studies, and also proposes more potential COX-2-mediated mechanisms. These events might contribute to the growth and progression of gastric cancer exposed to nicotine through tobacco smoke or cigarette substitutes. Also, this review article has therefore the potential not only to make a significant contribution to the treatment and prognosis of gastric cancer for smokers but also to the clinical application of COX-2 antagonists. In addition, this work also discusses the considerable challenges of this field with special reference to the future perspective of COX-2-mediated mechanisms in development and progression of gastric cancer induced by nicotine.


Asunto(s)
Receptores Nicotínicos , Neoplasias Gástricas , Humanos , Nicotina/toxicidad , Ciclooxigenasa 2/metabolismo , Neoplasias Gástricas/inducido químicamente , Neoplasias Gástricas/metabolismo , Receptores Nicotínicos/metabolismo , Fumar/efectos adversos
20.
Burns ; 50(2): 413-423, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37865601

RESUMEN

BACKGROUND: Patients with extensive burns are critically ill and have long treatment periods. Length of stay (LOS) is a good measure for assessing treatment. This study sought to identify predictors of prolonged LOS in patients with extensive burns (≥50% TBSA). METHODS: This retrospective multicenter cohort study included adults aged ≥ 18 years who survived extensive burns in three burn centers in Eastern China between January 2016 and June 2022. Epidemiological, demographic and clinical outcomes data were extracted from electronic medical records and compared between patients with/without prolonged LOS, which was defined as LOS greater than the median. Logistic regression analysis was used to identify predictors of prolonged LOS. RESULTS: The study sample included 321 patients, of whom 156 (48.6%) had an LOS of 58 days (IQR 41.0-77.0). Univariate regression analysis showed that increased total burn area and increased full-thickness burn area; electrical, chemical and other burns; increased erythrocytes, leukocytes, platelets or serum creatinine within 24 h of admission; concomitant inhalation injury, pulmonary edema, sepsis, bloodstream infection, wound infection, pulmonary infection, urinary tract infection, or HB < 70 g/L during hospitalization were associated with prolonged LOS in patients with extensive burns. Increased number of surgical operations, mechanical ventilation and renal replacement therapy were also associated with prolonged LOS (P < 0.05 or P < 0.001). Multivariate regression analysis revealed that increased total burn area (ratio 1.032, 95%CI 1.01-1.055; P = 0.004), electrical and chemical or other burns (3.282, 1.335-8.073; P = 0.01), development of wound infection (2.653 1.285-5.481; P = 0.008) and increased number of operative procedures (1.714, 1.388-2.116, P < 0.001) were significant predictors. CONCLUSIONS: Increased area of full-thickness burn,occurrence of electrical and chemical or other burns,occurrence of wound infection and increased number of surgeries are the best predictors of prolonged LOS in patients with extensive burns. Clarifying relevant predictors of burn patients' LOS provides a reliable reference for clinical treatment.


Asunto(s)
Quemaduras , Sepsis , Infección de Heridas , Adulto , Humanos , Tiempo de Internación , Estudios Retrospectivos , Estudios de Cohortes , Quemaduras/epidemiología , Quemaduras/terapia
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