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Anesthetic-induced developmental neurotoxicity (AIDN) can arise due to various factors, among which aberrant nerve cell death is a prominent risk factor. Animal studies have reported that repeated or prolonged anesthetic exposure can cause significant neuroapoptosis in the developing brain. Lately, non-apoptotic programmed cell deaths (PCDs), characterized by inflammation and oxidative stress, have gained increasing attention. Substantial evidence suggests that non-apoptotic PCDs are essential for neuronal cell death in AIDN compared to apoptosis. This article examines relevant publications in the PubMed database until April 2024. Only original articles in English that investigated the potential manifestations of non-apoptotic PCD in AIDN were analysed. Specifically, it investigates necroptosis, pyroptosis, ferroptosis, and parthanatos, elucidating the signaling mechanisms associated with each form. Furthermore, this study explores the potential relevance of these non-apoptotic PCDs pathways to the pathological mechanisms underlying AIDN, drawing upon their distinctive characteristics. Despite the considerable challenges involved in translating fundamental scientific knowledge into clinical therapeutic interventions, this comprehensive review offers a theoretical foundation for developing innovative preventive and treatment strategies targeting non-apoptotic PCDs in the context of AIDN.
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Anestésicos , Apoptosis , Síndromes de Neurotoxicidad , Humanos , Síndromes de Neurotoxicidad/patología , Síndromes de Neurotoxicidad/etiología , Animales , Anestésicos/efectos adversos , Anestésicos/toxicidad , Anestésicos/farmacología , Apoptosis/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/metabolismo , Piroptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Necroptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/crecimiento & desarrollo , Ferroptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Postpartum depression (PPD) is linked to hormonal changes. Brexanolone, the first FDA-approved drug for PPD, is a potential treatment. This study analyzes Brexanolone's safety using the FAERS database, highlighting its adverse effects and potential risk factors. METHODS: We analyzed FAERS data from Q3 2019 to Q3 2023, evaluating adverse reactions to Brexanolone. The analysis includes demographics, reporting regions, reporter identities, and types of adverse reactions. RESULTS: Most reports are from the United States, with consumers and physicians as primary reporters. Adverse reactions mainly involve severe systemic diseases, administration site reactions, injuries, intoxication, operational complications, and mental disorders. Specific adverse reactions include incorrect drug monitoring, PPD, intrusive thoughts, delayed treatment efficacy, sedation complications, product discontinuation, misuse, infusion site leakage and pain, and medication errors. CONCLUSION: The study confirms known safety information about Brexanolone and provides comprehensive data for medical practices and public health decisions. However, relying on spontaneous reports may introduce biases and incomplete information. Continued monitoring and reporting of adverse reactions to newer drugs like Brexanolone remain crucial.
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Background: The significant progress has been made in targeted therapy for lung adenocarcinoma (LUAD) in the past decade. Only few targeted therapeutics have yet been approved for the treatment of lung squamous cell carcinoma (LUSC). Several higher frequency of gene alterations are identified as potentially actionable in LUSC. Our work aimed to explore the complex interplay of multiple genetic alterations and pathways contributing to the pathogenesis of LUSC, with a very low frequency of a single driver molecular alterations to develop more effective therapeutic strategies in the future. Methods: We retrospectively analyzed the targeted next-generation sequencing (NGS) data (approximately 600 genes) of 335 patients initially diagnosed with non-small cell lung cancer (NSCLC) at our institution between January 2019 and March 2023 and explored the somatic genome alteration difference between LUSC and LUAD. Results: We analyzed that the presence of loss-of-function (LoF) mutations (nonsense, frameshift, and splice-site variants) in histone-lysine N-methyltransferase 2D (KMT2D) was much more prevalent in LUSC (11/53, 20.8%) than in LUAD (6/282, 2.1%). Moreover, our data indicated TP53 co-mutated with KMT2D LoF in 90.9% (10/11) LUSC and 33.3% (2/6) LUAD. Notably, the mutation allele fraction (MAF) of KMT2D was very similar to that of TP53 in the co-mutated cases. Genomic profiling of driver gene mutations of NSCLC showed that 81.8% (9/11) of the patients with LUSC with KMT2D LoF mutations had PIK3CA amplification and/or FGFR1 amplification. Conclusions: Our results prompted that somatic LoF mutations of KMT2D occur frequently in LUSC, but are less frequent in LUAD and therefore may potentially contribute to the pathogenesis of LUSC. Concurrent TP53 mutations, FGFR1 amplification, and PIK3CA amplification are very common in LUSC cases with KMT2D LoF mutations. It needs more deeper investigation on the interplay of the genes and pathways and uses larger cohorts in the future.
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Gliomas are typical malignant brain tumours affecting a wide population worldwide. Operation, as the common treatment for gliomas, is always accompanied by postoperative drug chemotherapy, but cannot cure patients. The main challenges are chemotherapeutic drugs have low blood-brain barrier passage rate and a lot of serious adverse effects, meanwhile, they have difficulty targeting glioma issues. Nowadays, the emergence of nanoparticles (NPs) drug delivery systems (NDDS) has provided a new promising approach for the treatment of gliomas owing to their excellent biodegradability, high stability, good biocompatibility, low toxicity, and minimal adverse effects. Herein, we reviewed the types and delivery mechanisms of NPs currently used in gliomas, including passive and active brain targeting drug delivery. In particular, we primarily focused on various hopeful types of NPs (such as liposome, chitosan, ferritin, graphene oxide, silica nanoparticle, nanogel, neutrophil, and adeno-associated virus), and discussed their advantages, disadvantages, and progress in preclinical trials. Moreover, we outlined the clinical trials of NPs applied in gliomas. According to this review, we provide an outlook of the prospects of NDDS for treating gliomas and summarise some methods that can enhance the targeting specificity and safety of NPs, like surface modification and conjugating ligands and peptides. Although there are still some limitations of these NPs, NDDS will offer the potential for curing glioma patients.
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This study aimed to investigate the impact of dexmedetomidine combined with ropivacaine on continuous femoral nerve block (CFNB) in postoperative analgesia and delirium in elderly patients with total knee arthroplasty (TKA). A total of 120 patients who undergone TKA were randomly assigned into group D + R (dexmedetomidine combined with ropivacaine) and group R (only ropivacaine), with 60 cases in each group. The pain scores at rest and exercise at 6 h, 12 h, 24 h, and 48 h postoperatively. The occurrence of delirium on Day 1, Day 2, and Day 3 postoperatively were measured, and the sleep quality was evaluated before surgery, the night of surgery, and 24 h postoperatively to observe the occurrence of postoperative complications. The Visual analogu scale (VAS) of group D + R at 12 h, 24 h, and 48 h postoperatively were lower than those of group R in both rest and exercise states. The incidence of postoperative delirium in group D + R was lower than that in group R on Day 1 and Day 2. Pittsburgh sleep quality index (PSQI) scores in group D + R were lower than those in group R. There was no significant difference in postoperative adverse reactions between the two groups. Dexmedetomidine combined with ropivacaine improves postoperative analgesia and sleep quality, and alleviates the occurrence of postoperative delirium in elderly patients with TKA.
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Analgesia , Artroplastia de Reemplazo de Rodilla , Dexmedetomidina , Delirio del Despertar , Procedimientos Quirúrgicos Robotizados , Anciano , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Dexmedetomidina/uso terapéutico , Ropivacaína , Procedimientos Quirúrgicos Robotizados/métodosRESUMEN
OBJECTIVE: Glucose metabolism plays a crucial role in the progression of Alzheimer's disease (AD). The purpose of this study is to identify genes related to glucose metabolism in AD by bioinformatics, construct an early AD prediction model from the perspective of glucose metabolism, and analyze the characteristics of immune cell infiltration. METHODS: AD-related modules and genes were screened by weighted gene co-expression network analysis (WGCNA). The GO and KEEG enrichment analysis were used to explore the potential biological functions of glucose metabolism related genes (GMRGs) in AD. The Least Absolute Shrinkage Selection Operator (LASSO) method was used to construct an early AD prediction model based on GMRGs. Then, the receiver operating characteristic curve (ROC) and nomogram were introduced to evaluate the effectiveness of this model. Finally, CIBERSORT and single-cell analysis were applied for illustrating the immune characteristics in AD patients. RESULTS: A total of 462 differential expressed genes (DEGs) were obtained between Non-Alzheimer's disease (ND,) and AD groups. The genes in the blue module had the highest correlation with AD by WGCNA analysis. We found 18 intersected genes among DEGs, blue model genes and GMRGs according to the Venn diagram. The GO and KEEG enrichment analysis showed that these 18 genes were mainly involved in the production of metabolites and energy, glycolysis, amino acid biosynthesis and so on. The early AD prediction model including ENO2, TPI1, AEBP1, HERC1, PCSK1, PREPL, SLC25A4, UQCRC2, CHST6, DDIT4, ACSS1 and SUCLA2 was constructed by LASSO analysis. The area under the curve (AUC) of this model in brain tissues was 0.942. Then, we draw the nomogram of this model and the C-index was 0.942. The model was further validated in blood samples and the AUC was 0.644. Immune cell infiltration analysis showed that the proportion of plasma cells, T cells follicular helper and activated NK cells in AD group were significantly lower than ND group, while the proportion of M1 macrophages, neutrophils, T cells CD4 naive and γ-δ T cells was significantly increased when compared with the ND group. Additionally, the specific GMRGs such as ENO2, DDIT4, and SUCLA2 are significantly correlated with certain immune cells such as plasma cells, follicular helper T cells, and M1 macrophages. Single-cell analysis results suggested that the increased macrophages in AD was associated with the up-regulation of AEBP1, DDIT4 and ACSS1. CONCLUSIONS: The diagnosis model based on the twelve GMRGs has strong predictive ability and can be used as early diagnosis biomarkers for AD. In addition, these GMRGs closely associate with AD development by influencing the glucose metabolism of immune cells.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/genética , Metabolismo de los Hidratos de Carbono , Glucólisis , Área Bajo la Curva , Glucosa , Carboxipeptidasas , Proteínas RepresorasRESUMEN
Nucleotide-binding leucine-rich repeat-containing receptor 12 (NLRP12), a highly conserved protein containing an N-terminal pyrin domain (PYD), a nucleotide-binding domain and a C-terminal leucine-rich repeat region, belongs to the nucleotide-binding oligomerization domain-like receptor-containing PYD (NLRP) family and is a cytoplasmic sensor that plays a negative role in inflammation. NLRP12 is involved in multiple disease processes, including formation of inflammasomes and regulation of both canonical and noncanonical inflammatory signaling pathways. NLRP12 and pathogenic infections are closely linked, and alterations in NLRP12 expression and activity are associated with inflammatory diseases. In this review, we begin with a summary of the mechanisms of negative regulation by NLRP12. We then underscore the important roles of NLRP12 in the onset and progression of inflammation, infectious disease, host defense, carcinogenesis and COVID-19. Finally, we highlight factors that influence NLRP12 activity, including synthetic and naturally derived agonists, and are regarded as potential therapeutic agents to overcome inflammatory diseases.
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COVID-19 , Péptidos y Proteínas de Señalización Intracelular , Humanos , Leucina , Inflamación , NucleótidosRESUMEN
Protein-polysaccharide interactions have attracted much attention due to inherent potential in generating new structures and functionalities. In the present study, by simply mixing rice proteins (RPs) with carboxymethyl cellulose (CMC) at pH 12.0 prior neutralization, novel protein-polysaccharide complexes (RCs) were structured with water dispersibility and functionalities highly dependent on the degree of substitution (DS) and molecular weight (Mw) of CMC. Specifically, the water-dispersibility of RPs was increased from 1.7 % to 93.5 % at a RPs/CMC mass ratio of 10:1 with CMC of DS1.2 (Mw = 250 kDa). Fluorescence and circular dichroism spectra showed suppressed folding tendency of RPs by CMC during neutralizing the basicity, indicating controllable protein conformations. Furthermore, the structures of RCs became more unfolded for CMC with a larger DS or a smaller Mw. This enabled RCs with highly controllable functionalities in terms of emulsifying and foaming properties, which may have promising applications in developing food matrix with customized structures and textures.
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Carboximetilcelulosa de Sodio , Oryza , Carboximetilcelulosa de Sodio/química , Oryza/química , Electricidad Estática , Proteínas de Plantas/química , Agua/químicaRESUMEN
Background: The transcription factors (TFs)-microRNA (miRNA)-messenger RNA (mRNA) network plays an important role in a variety of diseases. However, the relationship between the TFs-miRNA-mRNA network and idiopathic pulmonary fibrosis (IPF) remains unclear. Methods: The GSE110147 and GSE53845 datasets from the Gene Expression Omnibus (GEO) database were used to process differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), as well as Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The GSE13316 dataset was used to perform differentially expressed miRNAs (DEMs) analysis and TFs prediction. Finally, a TFs-miRNA-mRNA network related to IPF was constructed, and its function was evaluated by Gene Ontology (GO) and KEGG analyses. Also, 19 TFs in the network were verified by quantitative real time polymerase chain reaction (qRT-PCR). Results: Through our analysis, 53 DEMs and 2,630 DEGs were screened. The GSEA results suggested these genes were mainly related to protein digestion and absorption. The WGCNA results showed that these DEGs were divided into eight modules, and the GO and KEGG analyses results of blue module genes showed that these 86 blue module genes were mainly enriched in cilium assembly and cilium organization. Moreover, a TFs-miRNA-mRNA network comprising 25 TFs, 11 miRNAs, and 60 mRNAs was constructed. Ultimately, the functional enrichment analysis showed that the TFs-miRNA-mRNA network was mainly related to the cell cycle and the phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling pathway. Furthermore, experimental verification of the TFs showed that ARNTL, TRIM28, EZH2, BCOR, and ASXL1 were sufficiently up-regulated in the transforming growth factor (TGF)-ß1 treatment groups, while BCL6, BHLHE40, FOXA1, and EGR1 were significantly down-regulated. Conclusions: The novel TFs-miRNA-mRNA network that we constructed could provide new insights into the underlying molecular mechanisms of IPF. ARNTL, TRIM28, EZH2, BCOR, ASXL1, BCL6, BHLHE40, FOXA1, and EGR1 may play important roles in IPF and become effective biomarkers for diagnosis and treatment.
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Cryptocaryon irritans causes one of the most serious diseases in various wild and cultured marine fish, leading to mass mortality and economic loss. In this study, hydroxyl radical (â¢OH) solution produced by strong ionization discharge combined with water jet cavitation effect was injected into orange-spotted grouper (Epinephelus coioides) aquaculture tanks for C. irritans control. The results showed that all C. irritans theronts were inactivated by â¢OH solution at concentrations of 0.5 mg/L within 2 min. â¢OH could induce alteration of shape, the absence of motility and macronucleus dispersion in theronts. A possible explanation was that the macronucleus of C. irritans might be damaged by â¢OH; as a result, its metabolism and life activities were disturbed. The â¢OH treatment increased the survival rate of E. coioides challenged with C. irritans from 64.7 ± 8.0% (mean ± SD) to 100% and reduced their infection intensity significantly. Stress response biomarkers such as malonaldehyde, glutathione, glutathione peroxidase, superoxide dismutase (SOD) and catalase levels in the gills of E. coioides at different time points were analysed. The SOD activity in the â¢OH group first decreased and then recovered to the initial level at the end of the experiment. The other stress response biomarkers had no significant difference from that in the uninfected control group after â¢OH treatment. Additionally, the gill of E. coioides in the â¢OH group exhibited slight and reversible transformation compared with the uninfected control group. Compared with â¢OH treatment, chlorine dioxide and formalin treatment reduced the survival rate, induced oxidative damage and changed the histological gill structure in E. coioides. In conclusion, â¢OH could be applied effectively to control C. irritans infection without affecting the normal physiological condition of E. coioides.
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Lubina , Infecciones por Cilióforos , Cilióforos , Enfermedades de los Peces , Hymenostomatida , Animales , Cilióforos/fisiología , Infecciones por Cilióforos/metabolismo , Enfermedades de los Peces/metabolismo , Superóxido Dismutasa , Proteínas de Peces/metabolismoRESUMEN
Considering the prerequisite need for a protected e-commerce platform, absence of haptic interaction in head-mounted displays (HMD), and exploitation of faster communication technology, this research work aims to present an amended version of the tele-weight device that utilizes the 6G visible light communication (VLC) technology, is faster in performance, and deals with a heavier article. The enhanced version of the device is to be called the 'VLC tele-weight device' and the aim for the VLC tele-weight device is to get it affixed over the headset which will allow the user to have the weight-based sensation of the product ordered on the virtual store. The proposed device sending end and receiving end part performs communication over the VLC link. Furthermore, Arduino Nano is used as the microcontroller (MCU) in the project. Sending end circuitry measures the weight using the load cell and HX711 amplifier combination and transmits it via the connected LED. The pre-equalizer circuit is connected between the LED and sending end part to improve the bandwidth. On the receiver side, the post-equalizer circuit improves the shape of the received pulse. The received weight value is then displayed using the motor-gear combination. The sending end device is to be sited at the virtual store, while the receiving end is planned to be positioned over the VR headset. The performance of the device was measured by performing repeated trials and the percentage error was found to be between 0.5-3%. Merging the field of embedded systems, internet of things (IoT), VLC, signal processing, virtual reality (VR), e-commerce, and haptic sensing, the idea proposed in this research work can help introduce the haptic interaction, and sensational realization-based innovation in immersive visualization (IV) and graphical user interface (GUI) domain.
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BACKGROUND: Guillain-Barré syndrome (GBS) is a common peripheral neuropathy with relatively heterogenous clinical manifestations. In severe cases, it can result in disabling neuromuscular symptoms and respiratory failure. In this study, we assessed whether the systemic immune-inflammation index (SII) is associated with respiratory failure in GBS patients. METHODS: We retrospectively analyzed clinicopathological data from GBS patients diagnosed in the First Affiliated Hospital of Kunming Medical University. SII was calculated based on counts of neutrophils (N), platelets (P), and lymphocytes (L). Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values for SII, N, P, and L. Univariate and multivariate logistic regression were performed to determine the ability of the SII to predict respiratory failure. RESULTS: Among the 369 GBS patients in this study, 61 (16.5%) suffered respiratory failure. Multivariate logistic regression showed that N ≥ 6.03 × 109/l, Hughes Functional Grading Scale (HFGS) score ≥ 3 at admission, and SII ≥ 863.04 × 109/l can independently predict respiratory failure in GBS patients. SII showed higher predictive ability than N, based on area under the ROC curve (0.75 vs. 0.72). CONCLUSION: SII may be a novel independent prognostic indicator of respiratory failure in GBS patients, helping physicians identify those at risk in a timely manner.
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Síndrome de Guillain-Barré , Insuficiencia Respiratoria , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/epidemiología , Humanos , Inflamación , Linfocitos , Pronóstico , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/etiología , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the value of impulse oscillometry (IOS) and quantitative HRCT parameters for differentiating asthma-COPD overlap (ACO) in COPD patients. PATIENTS AND METHODS: We enrolled 44 controls and 66 COPD patients, divided into the pure COPD group (n=40) and the ACO group (n=26). Spearman correlation analysis was utilized to assess the relationship between the quantitative HRCT and IOS parameters. A binary logistic regression analysis was performed to analyze the associations between the different variables and the risk of ACO. Receiver operating characteristic (ROC) curves were employed to identify the optimal cutoff and assess the diagnostic value of relative volume change -856 HU to -950 HU (RVC-856 to -950), decrease in the resistance from 5 Hz to 20 Hz (R5-R20) and their combination in predicting ACO. Bootstrapping validation was used to evaluate the internal validation. The concordance index (C-index) and calibration plot were calculated to assess the discrimination and calibration of the prediction model. RESULTS: Binary logistic regression analysis indicated that RVC-856 to -950 and the IOS parameters (R5-R20, R5, X5) were independently correlated with a higher risk of developing ACO after adjusting for age, sex, body mass index (BMI), history of smoking, exacerbation and atopy or allergic rhinitis. A correlation analysis showed a good correlation between the pulmonary function parameters and RVC-856 to -950, with a weaker correlation with the % area of low attenuation (LAA%) in ACO patients. Combining RVC-856 to -950 and R5-R20 to predict ACO, the AUC was 0.909, and the optimal cutoff value was >-0.62 for RVC-856 to -950 and >0.09 for R5-R20. Good calibration and favorable discrimination were displayed with a higher C-index. CONCLUSION: More serious small airway impairment exists in ACO patients. The combination of RVC-856 to -950 and R5-R20 could be applied to differentiate ACO from COPD patients.
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Asma , Enfermedad Pulmonar Obstructiva Crónica , Asma/diagnóstico por imagen , Volumen Espiratorio Forzado , Humanos , Oscilometría , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , EspirometríaRESUMEN
Adding hydrocolloids into native starch is a secure and effective method of physical modification. In this study, the effect of sodium alginate (AG) on the gelatinization, rheological, and retrogradation properties of rice starch (RS) was investigated by measuring the pasting parameters, melting enthalpy (ΔH), rheological characteristic parameters, intensity ratio of 1047 cm-1 to 1022 cm-1 (R1047/1022), and relative crystallinity (RC) of RS-AG blends. Rapid visco analysis shows that AG could significantly change the gelatinization parameters of RS. Differential scanning calorimetry results show that the ΔH values of RS initially decreased in the low AG concentration range (0.10%-0.30%), but increased in the high AG concentration range (0.30%-0.50%). Dynamic rheological analysis reveals that the modulus (G', G'') and the loss tangent (tan δ) increased with the rise of the AG concentration from 0.10% to 0.50%. Fourier transform infrared spectroscopy and X-ray diffraction patterns collectively prove that the crystallinity of RS decreased with the addition of AG during the retrogradation periods. The interactions between AG and starch molecules in RS-AG blends were hypothesized to correlate with the aforementioned results.
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Alginatos/química , Gelatina/química , Oryza/química , Rastreo Diferencial de Calorimetría , Reología , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
OBJECTIVE: Magnesium sulfate is considered to be an effective adjuvant to rocuronium in general anaesthesia. We conducted a meta-analysis to clarify its efficacy. METHODS: We searched the PubMed, Embase, Web of Science, Cochrane Library, WanFang, Chinese Biomedical Literature, and China National Knowledge Infrastructure databases for randomized controlled trials (RCTs) of magnesium sulfate as an adjuvant to rocuronium from the start of the database establishment until May 2020. RESULTS: Eleven RCTs were analysed. The pooled meta-analysis showed that using magnesium sulfate as an adjuvant significantly shortened the onset time and prolonged the clinical duration of neuromuscular blockade by rocuronium compared with the control group without magnesium sulfate. However, there was no significant difference in recovery index of neuromuscular block between the magnesium and control groups. Furthermore, magnesium sulfate significantly increased the rates of excellent and clinically acceptable intubation conditions. CONCLUSION: Adding magnesium sulfate to rocuronium during general anaesthesia can alter the neuromuscular parameters, including shortening the anaesthesia-onset time and prolonging the clinical duration, without significantly increasing the recovery time. Pretreatment with magnesium sulfate may also improve intubation conditions during general anaesthesia.
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Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes , Androstanoles , Anestesia General , China , Humanos , Sulfato de Magnesio , RocuronioRESUMEN
OBJECTIVE: The lipopolysaccharide- (LPS-) induced acute intestinal dysfunction model has been widely applied in recent years. Here, our aim was to investigate the effect of triggering receptor expressed on myeloid cells-1 (TREM1) inhibitor in LPS-induced acute intestinal dysfunction. METHODS: Male rats were randomly assigned into normal (saline injection), model (LPS and saline injection), and LP17 (LPS and LP17 (a synthetic TREM1 inhibitor) injection) groups. The levels of intestinal TREM1 expression were evaluated by immunohistochemistry and western blot. Intestinal permeability and apoptosis were separately assessed by the lactulose/mannitol (L/M) ratio and TUNEL assay. The levels of soluble TREM1 (sTREM1), TNF-α, IL-6, and IL-1ß were measured in the plasma and intestinal tissues by ELISA. The expression levels of NF-κB, high-mobility group box 1 (HMGB1), and toll-like receptor 4 (TLR-4) were measured with RT-qPCR and western blot. After transfection with si-TREM1 in LPS-induced intestinal epithelium-6 (IEC-6) cells, p-p65 and p-IκBα levels were detected by western blot. RESULTS: LP17-mediated TREM1 inhibition alleviated the intestine tissue damage in rats with LPS-induced acute intestinal dysfunction. LP17 attenuated the LPS-induced increase in sTREM1, TNF-α, IL-6, and IL-1ß levels in the plasma and intestinal tissues. Furthermore, intestine permeability and epithelial cell apoptosis were ameliorated by LP17. LP17 attenuated the LPS-induced increase in the expression of TREM1, HMGB1, TLR-4, and NF-κB in the intestine tissues. In vitro, TREM1 knockdown inactivated the NF-κB signaling in LPS-induced IEC-6 cells. CONCLUSION: LP17 could ameliorate LPS-induced acute intestinal dysfunction, which was associated with inhibition of intestinal apoptosis and inflammation response.
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Apoptosis , Inflamación/patología , Intestinos/patología , Intestinos/fisiopatología , Receptor Activador Expresado en Células Mieloides 1/antagonistas & inhibidores , Enfermedad Aguda , Animales , Inflamación/complicaciones , Mucosa Intestinal/patología , Mucosa Intestinal/fisiopatología , Lipopolisacáridos , Masculino , FN-kappa B/metabolismo , Permeabilidad , Ratas Sprague-Dawley , Transducción de Señal , Receptor Activador Expresado en Células Mieloides 1/metabolismoRESUMEN
BACKGROUND: Pleomorphic adenoma (PA) is the most common benign tumor that occurs in the salivary glands; however, tracheobronchial PA is rarely observed. To the best of our knowledge, fewer than 50 cases have been reported in the literature. We report a 49-year-old woman who had been treated for asthma for 2 years before being diagnosed with PA of the trachea. CASE SUMMARY: A 49-year-old woman was referred to our hospital due to dyspnea upon exertion and chronic cough with wheezing for 2 years. Laboratory tests showed an elevated white blood cell count, absolute neutrophil count, and percentage of neutrophils. A chest computerized tomography scan showed a well-defined, soft-tissue density lesion measuring 2.4 cm × 2.1 cm in the lower trachea. Flexible bronchoscopy revealed that nearly 90% of the tracheal lumen was obstructed. The histopathological and immunohistochemistry features suggested PA of the trachea. Furthermore, we review the characteristics of 29 patients with tracheobronchial PA over the last 30 years. CONCLUSION: Tracheobronchial PA occurs without gender predominance, mostly in the lower or upper trachea, and has a low recurrence rate. The median age at diagnosis is 48 years. The most common symptoms are cough, stridor, dyspnea, and wheezing.
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Genetic Creutzfeldt-Jakob disease (gCJD) is characterized by mutations in the PRNP gene and represents approximately 10-15% of the human prion diseases. Here, we report a 42-year-old Chinese man who was diagnosed with gCJD. The patient had a rare mutation in codon 196 (E196A) of PRNP leading to an exchange of amino acid from glutamic acid (E) to alanine (A). The polymorphism of codon 129 in the patient was methionine homozygote. His mother and daughter are asymptomatic carriers of the same mutation. The clinical manifestations were similar to those of sporadic CJD. 14-3-3 protein was positive in cerebrospinal fluid, and there were sharp slow complex waves in electroencephalography and ribbon-like signals on magnetic resonance imaging (MRI). The main complaints of patient changed from visual space and visual colour to psychotic symptoms with enhanced high signal intensity on the occipital and frontal cortices on MRI. We compared the clinical characteristics of the current patient with those of previously reported Chinese patients with other gCJD of E196A mutation to summarize the common features of E196A gCJD.
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Síndrome de Creutzfeldt-Jakob/genética , Mutación/genética , Proteínas Priónicas/genética , Adulto , Secuencia de Bases , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagen , Electroencefalografía , Heterocigoto , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND AND OBJECTIVE: The distance of 6-minute walk test (D6MWT) has been widely used in the assessment of functional status in patients with COPD, while very little attention has been paid to the role of steps of 6-minute walk test (S6MWT). The purpose of this study was to investigate the relationship between S6MWT and other physiologic parameters of COPD. PATIENTS AND METHODS: Seventy patients with stable COPD were enrolled consecutively in this cross-sectional study. Pulmonary function tests, including spirometry, impulse oscillometry (IOS) and the single-breath diffusing capacity of the lungs for carbon monoxide (DLCO), were carried out at rest. Quality of life was assessed by health-related quality of life (HRQoL) questionnaires, including modified Medical Research Council dyspnea scale (mMRC), St George's Respiratory Questionnaire, Chronic Obstructive Pulmonary Disease Assessment Test (CAT) and Clinical Chronic Obstructive Pulmonary Questionnaire. Both steps and distance were measured in the following 6-minute walk test (6MWT). RESULTS: Both S6MWT and D6MWT showed significant correlation with spirometry, IOS, DLCO parameters and HRQoL questionnaires score. Both pre- and post-6MWT inspiratory capacity showed significant correlation with S6MWT (ρ=0.338, P=0.004; ρ=0.359, P=0.002, respectively), whereas did not correlate with D6MWT (ρ=0.145, P=0.230; ρ=0.160, P=0.189, respectively). In stepwise multiple regression analysis, mMRC grade, age and CAT score remained as significant predictors in the final model for D6MWT (adjusted R 2=0.445, P<0.01). DLCO and CAT score remained as significant predictors in the final model for S6MWT (adjusted R 2=0.417, P<0.01). CONCLUSION: S6MWT is efficient in the evaluation of functional status and quality of life in COPD and has significant correlation with various parameters indicating disease severity. Additionally, S6MWT might be better in predicting lung hyperinflation in COPD compared with D6MWT.
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Tolerancia al Ejercicio , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Prueba de Paso , Caminata , Anciano , Estudios Transversales , Femenino , Volumen Espiratorio Forzado , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Oscilometría , Valor Predictivo de las Pruebas , Pronóstico , Capacidad de Difusión Pulmonar , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Índice de Severidad de la Enfermedad , Espirometría , Encuestas y Cuestionarios , Capacidad VitalRESUMEN
OBJECTIVE: To investigate the use of citrulline as an indicator for diagnosing septic acute intestinal dysfunction (SAID) in a rat model. METHODS: SD rats were divided into three groups: a normal group (A), a model group (B), and a glutamine group (C). Group B was divided into a 36-h group (B1) and a 72-h feeding group (B2). The concentrations of serum citrulline, intestinal fatty acid-binding protein (I-FABP) and intestinal glutamine and histopathological changes were measured. RESULTS: The lengths of the villus and thicknesses of the mucosal layer in groups B1, B2 and C were significantly different from those in group A. Citrulline concentrations in groups B1, B2 and C were lower than in group A; the serum concentrations in group C were significantly greater than in groups B1 and B2. The I-FABP levels of groups B1, B2 and C were higher than group A; I-FABP levels of groups B1 and B2 were higher than group C. Intestinal glutamine levels of groups B1 and B2 were lower than groups A and C. The serum citrulline of group C was negatively correlated with I-FABP and Chiu's score. CONCLUSIONS: Serum citrulline could be used as the diagnostic indicator of SAID.