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Objective: This research aims to investigate the prognosis value using the time-weighted average neutrophil-to-lymphocyte ratio (TWA-NLR) for predicting all-cause hospital mortality among sepsis patients. Data were analyzed through the use of the eICU Collaborative Research Database (eICU-CRD 2.0) as well as Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2). Methods: Septic patients from both eICU-CRD 2.0 as well as MIMIC-IV 2.2 databases were included. The neutrophil-to-lymphocyte ratios (NLR) were available for analysis, utilizing complete blood counts obtained on days one, four, and seven following ICU admission. The TWA-NLR was computed at the end of the seven days, and patients were then stratified based on TWA-NLR thresholds. 90-day all-cause mortality during hospitalization was the primary objective, with 60-day all-cause hospital mortality as a secondary objective. The correlation between TWA-NLR and sepsis patients' primary outcome was analyzed using univariable and multivariable Cox proportional hazard regressions. A restricted cubic spline (RCS) analysis was conducted in an attempt to confirm this association further, and subgroup analyses were employed to evaluate the correlation across various comorbidity groups. Results: 3921 patients were included from the eICU-CRD 2.0, and the hospital mortality rate was 20.8 %. Both multivariable as well as univariable Cox proportional hazard regression analyses revealed that TWA-NLR was independently correlated with 90-day all-cause hospital mortality, yielding a hazard ratio (HR) of 1.02 (95 % CI 1.01-1.02, P-value<0.01) as well as 1.12 (95 % CI 1.01-1.15, P-value<0.01), respectively. The RCS analysis demonstrated a significant nonlinear relationship between TWA-NLR and 90-day all-cause hospital mortality risk. The study subjects were divided into higher (>10.5) and lower (≤10.5) TWA-NLR cohorts. A significantly decreased incidence of 90-day all-cause hospital mortality (HR = 0.56, 95 % CI 0.48-0.64, P-value<0.01) and longer median survival time (40 days vs 24 days, P-value<0.05) were observed in the lower TWA-NLR cohort. However, septic patients with chronic pulmonary (interaction of P-value = 0.009) or renal disease (interaction of P-value = 0.008) exhibited significant interactive associations between TWA-NLR and 90-day all-cause hospital mortality, suggesting the predictive power of TWA-NLR may be limited in these subgroups. The MIMIC-IV 2.2 was utilized as a validation cohort and exhibited a similar pattern. Conclusion: Our findings suggest that TWA-NLR is a powerful and independent prognostic indicator for 90-day all-cause hospital mortality among septic patients, and the TWA-NLR cutoff value may prove a useful method for identifying high-risk septic patients.

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BACKGROUND: In sepsis, the relationship between lymphocyte counts and patient outcomes is complex. Lymphocytopenia and lymphocytosis significantly influence survival, illustrating the dual functionality of lymphocytes in responding to infections. This study investigates this complex interaction, focusing on how variations in lymphocyte counts correlate with all-cause hospital mortality among sepsis patients. METHODS: This retrospective cohort study analyzed data from two extensive critical care databases: the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV 2.0) from Beth Israel Deaconess Medical Center, Boston, Massachusetts, and the eICU Collaborative Research Database (eICU-CRD), which was Multi-center database from over 200 hospitals across the United States conducted by Philips eICU Research Institute. We included adult patients aged 18 years and older who met the Sepsis-3 criteria, characterized by documented or suspected infection and a Sequential Organ Failure Assessment (SOFA) score of 2 or higher. Sepsis patients were categorized into quartiles based on lymphocyte counts. The primary outcome was all-cause mortality in the hospital, with 90 and 60-day all-cause mortality as the secondary outcomes. Univariable and multivariable Cox proportional hazard regressions were utilized to assess lymphocyte counts' impact on hospital mortality. An adjusted restricted cubic spline (RCS) analysis was performed to elucidate this relationship further. Subgroup analyses were also conducted to explore the association across various comorbidity groups among sepsis and septic shock patients. RESULTS: Our study included 37,054 patients, with an observed in-hospital mortality rate of 16.6%. Univariable and multivariable Cox proportional hazard regression models showed that lymphocyte counts were independently associated with in-hospital mortality (HR = 1.04, P < 0.01; HR = 1.06, P < 0.01). RCS regression analysis revealed a U-shaped relationship between lymphocyte levels and hospital mortality risk in sepsis and septic shock patients (P for overall < 0.001, P for nonliner < 0.01; P for overall = 0.002, P for nonliner = 0.014). Subgroup analyses revealed that elevated lymphocyte counts correlated with increased hospital mortality among sepsis patients with liver disease and requiring renal replacement therapy (P for overall = 0.021, P for nonliner = 0.158; P for overall = 0.025, P for nonliner = 0.759). These findings suggest that lymphocytes may have enhanced prognostic value in specific subsets of critically ill sepsis patients. CONCLUSION: Our findings demonstrate that lymphocyte counts are a significant independent predictor of hospital mortality in sepsis and septic shock patients. We observed a U-shaped association between lymphocyte levels and mortality risk, indicating that high and low counts are linked to increased mortality. This result highlights the complex role of lymphocytes in sepsis outcomes and suggests the need for further investigation into the underlying mechanisms and potential therapeutic approaches. Integrating lymphocyte count assessment into risk stratification algorithms and clinical decision support tools could enhance the early identification of high-risk sepsis patients.

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BACKGROUND: This study aimed to explore the characteristics of abnormal regional resting-state functional magnetic resonance imaging (rs-fMRI) activity in comatose patients in the early period after cardiac arrest (CA), and to investigate their relationships with neurological outcomes. We also explored the correlations between jugular venous oxygen saturation (SjvO2) and rs-fMRI activity in resuscitated comatose patients. We also examined the relationship between the amplitude of the N20-baseline and the rs-fMRI activity within the intracranial conduction pathway of somatosensory evoked potentials (SSEPs). METHODS: Between January 2021 and January 2024, eligible post-resuscitated patients were screened to undergo fMRI examination. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) of rs-fMRI blood oxygenation level-dependent (BOLD) signals were used to characterize regional neural activity. Neurological outcomes were evaluated using the Glasgow-Pittsburgh cerebral performance category (CPC) scale at 3 months after CA. RESULTS: In total, 20 healthy controls and 31 post-resuscitated patients were enrolled in this study. The rs-fMRI activity of resuscitated patients revealed complex changes, characterized by increased activity in some local brain regions and reduced activity in others compared to healthy controls (P < 0.05). However, the mean ALFF values of the whole brain were significantly greater in CA patients (P = 0.011). Among the clusters of abnormal rs-fMRI activity, the cluster values of ALFF in the left middle temporal gyrus and inferior temporal gyrus and the cluster values of ReHo in the right precentral gyrus, superior frontal gyrus and middle frontal gyrus were strongly correlated with the CPC score (P < 0.001). There was a strong correlation between the mean ALFF and SjvO2 in CA patients (r = 0.910, P < 0.001). The SSEP N20-baseline amplitudes in CA patients were negatively correlated with thalamic rs-fMRI activity (all P < 0.001). CONCLUSIONS: This study revealed that abnormal rs-fMRI BOLD signals in resuscitated patients showed complex changes, characterized by increased activity in some local brain regions and reduced activity in others. Abnormal BOLD signals were associated with neurological outcomes in resuscitated patients. The mean ALFF values of the whole brain were closely related to SjvO2 levels, and changes in the thalamic BOLD signals correlated with the N20-baseline amplitudes of SSEP responses. TRIAL REGISTRATION: NCT05966389 (Registered July 27, 2023).

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Coma , Paro Cardíaco , Imagen por Resonancia Magnética , Sobrevivientes , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos , Persona de Mediana Edad , Coma/fisiopatología , Coma/diagnóstico por imagen , Paro Cardíaco/complicaciones , Paro Cardíaco/fisiopatología , Anciano , Sobrevivientes/estadística & datos numéricos , Estudios de Cohortes , Descanso/fisiología , Adulto

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Introduction: Gansu Province is situated in the northwest region of China, characterized by diverse and complex topography and a rich diversity of ethnic groups. This study aims to explore the prevalence and risk factors of adolescent suspected scoliosis in Gansu Province through a cross-sectional population study. Methods: From April 2022 to July 2022, a prospective cross-sectional study was conducted in Baiyin City, Jinchang City, Lanzhou City, Linxia Hui Autonomous Prefecture, and Gannan Tibetan Autonomous Prefecture in Gansu Province. The screening covered 3,118 middle and high school students across 24 institutions, including middle and high schools. Diagnosis of suspected scoliosis was established through visual inspection, the Adams forward bend test, and measurement of trunk rotation angle. Employing a custom-designed questionnaire, demographic data were collected, and the prevalence of suspected scoliosis was calculated. Univariate and multivariate logistic regression analyses were employed to assess factors associated with suspected scoliosis. Results: A total of 3,044 participants were ultimately included in the analysis. The overall prevalence of suspected scoliosis was 5.68% in Gansu Province. The peak prevalence for boy is at 14 years (6.70%), while for girl, it is at 15 years (8.75%). Lanzhou City exhibits the highest prevalence rates (boy, 9.82%; girl, 10.16). The results of univariate logistic regression analysis presented that BMI (OR = 0.92, 95% CI: 0.88-0.96), altitude of habitation (1,600 m-2000 m) (OR = 0.50, 95% CI: 0.34-0.73), altitude of habitation (2000 m-3321 m) (OR = 0.58, 95% CI: 0.40-0.83), family medical history (OR = 1.56, 95% CI: 1.02-2.31), and shoulders of unequal height (OR = 1.49, 95% CI: 1.09-2.03) were significantly correlated with suspected scoliosis. The multivariate logistic regression analysis indicated that BMI (OR = 0.91, 95% CI: 0.86-0.95), altitude of habitation (1,600 m-2000 m) (OR = 0.35, 95% CI: 0.23-0.54), altitude of habitation (2000 m-3321 m) (OR = 0.39, 95% CI: 0.24-0.60), family medical history (OR = 1.66, 95% CI:1.08-2.49), and shoulders of unequal height (OR = 1.45, 95% CI:1.06-1.99) were independently associated with suspected scoliosis. Conclusion: Low BMI, residence at an altitude of 1,600 m-3321 m, family medical history, and shoulders of unequal height were independently associated with an increased prevalence of suspected scoliosis. It is recommended to promptly screen high-risk adolescents for suspected scoliosis, provide effective preventive and intervention measures.

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Escoliosis , Humanos , Escoliosis/epidemiología , China/epidemiología , Adolescente , Estudios Transversales , Femenino , Masculino , Prevalencia , Factores de Riesgo , Estudios Prospectivos , Encuestas y Cuestionarios , Niño

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Laser-induced plasma micromachining (LIPMM) is an advanced technology that utilizes the plasma generated from laser breakdown to remove material, thereby facilitating the fabrication of microstructures. This paper explores the use of LIPMM on 304 stainless steel surfaces parallel to the laser beam in different solutions, focusing on the impact of the liquid environment on the machining process. It presents a theoretical analysis of the material removal mechanisms unique to this orientation and experimentally investigates how water, a salt solution, and ethanol affect plasma shockwave characteristics. Notably, the plasma shockwave in the salt solution demonstrates the most significant peak pressure and energy, enhancing the micromachining efficiency. These findings suggest that varying the liquid environment can significantly influence LIPMM's effectiveness, offering potential improvements in precision and control. This study broadens the understanding of LIPMM applications, especially in orientations not commonly explored, and opens new possibilities for advanced micromachining techniques in various industrial applications.

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As the outermost layer of the human body, the skin suffers from various external factors especially light damage, among which ultraviolet B (UVB) irradiation is common and possesses a relatively high biological damage capacity. Pyroptosis is a newly discovered type of programmed cell death, which can induce cell rupture and induce local inflammatory response. However, the molecular mechanisms of pyroptosis in photodamaged skin is poorly understood. Baicalin, a flavonoid extracted from the desiccated root of Scutellaria baicalensis Georgi (Huang Qin). Despite its antioxidant abilities, whether baicalin protects skin by attenuating UVB-induced pyroptosis remains unclear, which was the aim of this study. The UVB-induced acute skin damage model was established by using human immortalized keratinocytes (HaCaT cells) and Kunming (KM) strain mice. The protective dose selection for baicalin is 50 µM in vitro and 100 mg/kg in vivo. In in vitro study, UVB irradiation significantly decreased cell viability, increased cell death and oxidative stress in HaCaT cells, while pretreatment with baicalin improved these phenomena. Furthermore, the baicalin pretreatment notably suppressed nuclear factor kappa B (NF-κB) translocation, the NLRP3 inflammasome activation and gasdermin D (GSDMD) maturation, thus effectively attenuating UVB-induced pyroptosis. In in vivo study, the baicalin pretreatment mitigated epidermal hyperplasia, collagen fiber fragmentation, oxidative stress and pyroptosis in UVB-irradiated mouse skin. In a nutshell, this study suggests that baicalin could be a potential protective agent to attenuate acute skin damage induced by UVB irradiation through decreasing oxidative stress and suppressing NF-κB/NLRP3/GSDMD-involved pyroptosis.

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Flavonoides , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Piel , Rayos Ultravioleta , Piroptosis/efectos de los fármacos , Piroptosis/efectos de la radiación , Flavonoides/farmacología , Flavonoides/química , Animales , Humanos , Ratones , Piel/efectos de la radiación , Piel/efectos de los fármacos , Piel/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Queratinocitos/efectos de los fármacos , Queratinocitos/efectos de la radiación , Queratinocitos/metabolismo , Células HaCaT , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Proteínas de Unión a Fosfato/metabolismo , Inflamasomas/metabolismo , Línea Celular

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Background: Sepsis and sepsis-associated acute kidney injury (SA-AKI) pose significant global health challenges, necessitating the development of innovative therapeutic strategies. Dysregulated protein expression has been implicated in the initiation and progression of sepsis and SA-AKI. Identifying potential protein targets and modulating their expression is crucial for exploring alternative therapies. Method: We established an SA-AKI rat model using cecum ligation perforation (CLP) and employed differential proteomic techniques to identify protein expression variations in kidney tissues. Aldose reductase (AKR1B1) emerged as a promising target. The SA-AKI rat model received treatment with the aldose reductase inhibitor (ARI), epalrestat. Blood urea nitrogen (BUN) and creatinine (CRE) levels, as well as IL-1ß, IL-6 and TNF-α levels in the serum and kidney tissues, were monitored. Hematoxylin-eosin (H-E) staining and a pathological damage scoring scale assessed renal tissue damage, while protein blotting determined PKC (protein kinase C)/NF-κB pathway protein expression. Result: Differential proteomics revealed significant downregulation of seven proteins and upregulation of 17 proteins in the SA-AKI rat model renal tissues. AKR1B1 protein expression was notably elevated, confirmed by Western blot. ARI prophylactic administration and ARI treatment groups exhibited reduced renal injury, low BUN and CRE levels and decreased IL-1ß, IL-6 and TNF-α levels compared to the CLP group. These changes were statistically significant (P < 0.05). AKR1B1, PKC-α, and NF-κB protein expression levels were also lowered in the ARI prophylactic administration and ARI treatment groups compared to the CLP group (P < 0.05). Conclusions: Epalrestat appeared to inhibit the PKC/NF-κB inflammatory pathway by inhibiting AKR1B1, resulting in reduced inflammatory cytokine levels in renal tissues and blood. This mitigated renal tissue injuries and improved the systemic inflammatory response in the severe sepsis rat model. Consequently, AKR1B1 holds promise as a target for treating sepsis-associated acute kidney injuries.

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Lesión Renal Aguda , Sepsis , Animales , Ratas , Lesión Renal Aguda/tratamiento farmacológico , Aldehído Reductasa , Interleucina-6 , FN-kappa B , Proteómica , Sepsis/complicaciones , Factor de Necrosis Tumoral alfa

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Objective: To observe the effects of traditional Chinese medicine (TCM) five-element music therapy combined with mirtazapine on depression and limb function recovery after ischemic stroke. Methods: A total of 110 patients treated in the Departments of Geriatrics, Cardiology, and Psychology of three hospitals in Qinhuangdao City, Hebei Province, China from October 2022 to August 2023 were selected. Based on the scores of 24-item Hamilton Depression Scale (HAMD-24), Barthel (BL) index, and National Institute of Health Stroke Scale (NIHSS) before enrollment, the patients were randomly divided into control group (n = 58) and experimental group (n = 52). The patients in control group were treated with limb rehabilitation, while those in experimental group underwent limb rehabilitation combined with five-element music therapy and mirtazapine. Results: After 12 weeks of treatment and observation, 11 patients in control group and 9 patients in experimental group withdrew from this trail. As for the proportions of score changes, experimental group had higher decline proportions of HAMD-24 score and NIHSS score as well as an increased proportion of BL index score than control group, which were 43.97%, 69.32%, and 44.12%, respectively. Conclusion: TCM five-element music therapy combined with mirtazapine significantly improves depression and limb function recovery after ischemic stroke.

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We explored the effect of thrombin on human aortic smooth muscle cells (HASMCs) and further analyzed its role in the pathogenesis of atherosclerosis (AS). Thrombin-induced differentially expressed genes (DEGs) in HASMCs were identified by analyzing expression profiles from the GEO. Subsequently, enrichment analysis, GSEA, PPI network, and gene-microRNAs networks were interrogated to identify hub genes and associated pathways. Enrichment analysis results indicated that thrombin causes HASMCs to secrete various pro-inflammatory cytokines and chemokines, exacerbating local inflammatory response in AS. Moreover, we identified 9 HUB genes in the PPI network, which are closely related to the inflammatory response and the promotion of the cell cycle. Additionally, we found that thrombin inhibits lipid metabolism and autophagy of HASMCs, potentially contributing to smooth muscle-derived foam cell formation. Our study deepens a mechanistic understanding of the effect of thrombin on HASMCs and provides new insight into treating AS.

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Aterosclerosis , Transcriptoma , Humanos , Trombina/genética , Trombina/metabolismo , Trombina/farmacología , Aterosclerosis/patología , Miocitos del Músculo Liso/metabolismo , Músculo Liso/metabolismo , Músculo Liso/patología

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BACKGROUND: During ischemic stroke treatment, cerebral ischemia/reperfusion (I/R) injury results in neuronal cell death and neurological dysfunctions in brain. Previous studies indicate that basic helix-loop-helix family member e40 (BHLHE40) exerts protective effects on the pathology of neurogenic diseases. However, the protective function of BHLHE40 in I/R is unclear. OBJECTIVES: This study aimed to explore the expression, role and potential mechanism of BHLHE40 after ischemia. MATERIAL AND METHODS: We established models of I/R injury in rats and of oxygen-glucose deprivation/reoxygenation (OGD/R) in primary hippocampal neurons. Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to detect neuronal injury and apoptosis. Immunofluorescence was used to detect BHLHE40 expression. Cell viability and cell damage measurements were conducted using Cell Counting Kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) assay. The regulation of BHLHE40 to pleckstrin homology-like domain family A, member 1 (PHLDA1) was assessed using the dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay. RESULTS: Cerebral I/R rats exhibited severe neuronal loss and apoptosis in hippocampal cornu Ammonis 1 (CA1) region, accompanied by downregulated BHLHE40 expression at both mRNA and protein levels, indicating that BHLHE40 may regulate the apoptosis of hippocampal neurons. The function of BHLHE40 in neuronal apoptosis during cerebral I/R was further explored by establishing an OGD/R model in vitro. Low expression of BHLHE40 was also observed in neurons treated with OGD/R. The OGD/R administration inhibited cell viability and enhanced cell apoptosis in hippocampal neurons, whereas BHLHE40 overexpression reversed those changes. Mechanistically, we demonstrated that BHLHE40 could repress PHLDA1 transcription by binding to PHLDA1 promoter. The PHLDA1 is a facilitator of neuronal damage in brain I/R injury and its upregulation reversed the effects caused by BHLHE40 overexpression in vitro. CONCLUSIONS: The transcription factor BHLHE40 may protect against brain I/R injury through repressing cell damage via regulating PHLDA1 transcription. Thus, BHLHE40 may be a candidate gene for further study of molecular or therapeutic targets for I/R.

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Isquemia Encefálica , Daño por Reperfusión , Ratas , Animales , Apoptosis/genética , Daño por Reperfusión/genética , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Isquemia Encefálica/genética , Regulación hacia Arriba , Oxígeno/metabolismo , Glucosa

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Acute lung injury is a major cause of death in sepsis. Tofacitinib (TOFA), a JAK inhibitor, has anti-inflammatory activity in autoimmune diseases, but its role in acute lung injury in sepsis remains unclear. The purpose of this study is to establish a septic rat model by cecal ligation and perforation, and to evaluate the effect of tofacitinib on the survival rate of septic rat model and its role in acute lung injury in septic rats and the possible mechanism of action. In this study, TOFA (1 mg/kg, 3 mg/kg, 10 mg/kg) was used to observe the survival rate of septic rats. It was found that TOFA (10 mg/kg) significantly improved the survival rate of septic rats. We selected TOFA (10 mg/kg) and focused on the protective effect of TOFA on acute lung injury. The results confirmed that TOFA significantly inhibited the expression of TNF-α, IL-1ß, IL-6 and IFN-γ inflammatory factors, reduced the W/D weight ratio of septic lung tissue, and significantly improved lung histopathological damage. These results may be related to the inhibitory effect of TOFA on JAK-STAT/NF-κ B signaling pathway. In conclusion, for the first time, we found that TOFA has a protective effect against sepsis-induced acute lung injury, and it may be a promising drug for the treatment of acute lung injury in sepsis.

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Secukinumab is a specific neutralizing antibody for IL-17A. At present, numerous studies have confirmed the important role of IL-17A in sepsis, but the role of secukinumab in sepsis has not been studied. The present study explored the protective effect and underlying mechanism of secukinumab in severe sepsis model rats. We established a severe sepsis rat model using cecal ligation and puncture (CLP). The optimal dose of secukinumab was determined by observing the 7-day survival rate of severe sepsis model rats. The expression levels of TNF-α, IL-6, and IL-17A in plasma and lung tissue were determined by enzyme-linked immunosorbent assay. The degree of pathological damage to lung tissue was evaluated by hematoxylin-eosin (H-E) staining and pathological damage scale. The expressions of IKBα/NFκB pathway proteins and downstream-related inflammatory factors were detected by western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). Our results show that high-dose secukinumab can inhibit the activation of the IKBα/NFκB inflammatory pathway by neutralizing IL-17A and reducing the gene expression of pathway-related inflammatory cytokines, thereby reducing the levels of inflammatory cytokines in lung tissue and plasma, thereby reducing the damage of lung tissue in severe sepsis model rats and improving the systemic inflammatory response.

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Interleucina-17 , Sepsis , Animales , Anticuerpos Monoclonales Humanizados , Anticuerpos Neutralizantes/farmacología , Anticuerpos Neutralizantes/uso terapéutico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Eosina Amarillenta-(YS) , Hematoxilina , Interleucina-17/genética , Interleucina-6 , Ratas , Sepsis/tratamiento farmacológico , Transducción de Señal , Factor de Necrosis Tumoral alfa

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BACKGROUND: Pain catastrophizing in preoperative total knee arthroplasty (TKA) patients is associated with several poorly characterised factors in the literature. This study investigated the current state and associated factors of preoperative pain catastrophizing in patients undergoing TKA. METHODS: This descriptive cross-sectional study was conducted at the orthopedics ward of two tertiary hospitals in Lanzhou, China. Pain catastrophizing was measured using the Chinese versions of the Pain Catastrophizing Scale, Short Form-36 (physical function domain), Numerical Rating Scale, Oxford Knee Score, Hospital Anxiety and Depression Scale, and Life Orientation Test-Revised. RESULTS: The study included 360 participants. Preoperative TKA pain catastrophizing in all patients was high, with a mean score of 24.92 (SD: 12.38). The stepwise multiple linear regression analysis revealed anxiety (ß = 0.548, P < 0.01), education level (ß = - 0.179, P < 0.01), physical function (ß = - 0.156, P < 0.01), and pain intensity during activity (ß = 0.105, P = 0.015) as associated factors for pain catastrophizing, possibly explaining 51.2% of the total variation (F = 95.149, P < 0.01). CONCLUSION: Anxiety was the most relevant factor for pain catastrophizing in patients with preoperative TKA. Lower education levels, poor physical function, and stronger pain intensity during the activity were also associated with pain catastrophizing.

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Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Artroplastia de Reemplazo de Rodilla/efectos adversos , Catastrofización , China/epidemiología , Estudios Transversales , Humanos , Osteoartritis de la Rodilla/complicaciones , Dolor/cirugía

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The adjustable conductance of a two-terminal memristor in a crossbar array can facilitate vector-matrix multiplication in one step, making the memristor a promising synapse for efficiently implementing neuromorphic computing. To achieve controllable and gradual switching of multi-level conductance, important for neuromorphic computing, a theoretical design of a superlattice-like (SLL) structure switching layer for the multi-level memristor is proposed and validated, refining the growth of conductive filaments (CFs) and preventing CFs from the abrupt formation and rupture. Ti/(HfOx /AlOy )SLL /TiN memristors are shown with transmission electron microscopy , X-ray photoelectron spectroscopy , and ab initio calculation findings corroborate the SLL structure of HfOx /AlOy film. The optimized SLL memristor achieves outstanding conductance modulation performance with linearly synaptic weight update (nonlinear factor α = 1.06), and the convolutional neural network based on the SLL memristive synapse improves the handwritten digit recognition accuracy to 94.95%. Meanwhile, this improved synaptic device has a fast operating speed (30 ns), a long data retention time (≥ 104 s at 85 â„ƒ), scalability, and CMOS process compatibility. Finally, its physical nature is explored and the CF evolution process is characterized using nudged elastic band calculations and the conduction mechanism fitting. In this work, as an example the HfOx /AlOy SLL memristor provides a design viewpoint and optimization strategy for neuromorphic computing.

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Conductividad Eléctrica , Humanos , Redes Neurales de la Computación , Sinapsis

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Lesión Renal Aguda , Encefalopatías , Mordeduras y Picaduras de Insectos , Síndromes de Neurotoxicidad , Avispas , Animales , Encefalopatías/complicaciones , Humanos , Mordeduras y Picaduras de Insectos/complicaciones , Síndromes de Neurotoxicidad/complicaciones

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The rise of emerging technologies such as Big Data, the Internet of Things, and artificial intelligence, which requires efficient power schemes, is driving brainstorming in data computing and storage technologies. In this study, merely relying on the fundamental structure of two memristors and a resistor, arbitrary Boolean logic can be reconfigured and calculated in two steps, while no additional voltage sources are needed beyond "±VP " and 0, and all state reversals are based on memristor set switching. Utilizing the proposed logic scheme in an elegant form of unity structure and minimum cost, the implementation of a 1-bit adder is demonstrated economically, and a promising circuit scheme for the N-bit adder is exhibited. Some critical issues including the crosstalk problem, energy consumption, and peripheral circuits are further simulated and discussed. Compared with existing works on memristive logic, such methods support building a memristor-based digital in-memory calculation system with high functional reconfigurability, simple voltage sources, and low power and area consumption.

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Inspired by natural creatures, superhydrophobic surfaces with various adhesion behaviors have attracted significant scientific interest. In this study, by controlling the laser fluence, the scanning times, and the subsequent cleaning method, microcolumn arrays with different morphologies were fabricated on 304 stainless-steel surfaces using picosecond laser direct writing. To achieve wettability transition, the laser-processed samples were then subjected to heat treatments (120 °C) in air and in a low vacuum environment (6 kPa). The results show that after heat treatment in different environments and with various time lengths, the laser-processed surfaces become hydrophobic surfaces with different adhesion properties. It is worth noting that while surfaces heat-treated in air exhibit weak wettability transition potential and high adhesion, the surfaces heat-treated in a low vacuum environment present superhydrophobic and low adhesion properties with a minimum sliding angle of about 3.14°. Moreover, the low-vacuum heat-treated surfaces retain good superhydrophobic properties after 1 month of observation as well as an abrasion test. These transitions in hydrophobic behavior and adhesion properties may be mainly attributed to the heat treatment-induced (in the air or in a low vacuum environment) redistribution of surface compounds and the microstructure-induced alternation of the solid-liquid contact state. By controlling the laser processing parameters and the heat treatment time and environment, stable wettability transition and flexible adhesion control of stainless steel can be easily achieved.

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that places a heavy strain on public health. Host susceptibility to Mtb is modulated by macrophages, which regulate the balance between cell apoptosis and necrosis. However, the role of molecular switches that modulate apoptosis and necrosis during Mtb infection remains unclear. Here, we show that Mtb-susceptible mice and TB patients have relatively low miR-342-3p expression, while mice with miR-342-3p overexpression are more resistant to Mtb. We demonstrate that the miR-342-3p/SOCS6 axis regulates anti-Mtb immunity by increasing the production of inflammatory cytokines and chemokines. Most importantly, the miR-342-3p/SOCS6 axis participates in the switching between Mtb-induced apoptosis and necrosis through A20-mediated K48-linked ubiquitination and RIPK3 degradation. Our findings reveal several strategies by which the host innate immune system controls intracellular Mtb growth via the miRNA-mRNA network and pave the way for host-directed therapies targeting these pathways.

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MicroARNs , Mycobacterium tuberculosis , Tuberculosis , Animales , Muerte Celular , Humanos , Inflamación/genética , Ratones , MicroARNs/genética , Mycobacterium tuberculosis/genética , Proteínas Supresoras de la Señalización de Citocinas , Tuberculosis/genética

RESUMEN

BACKGROUND: Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear. RESEARCH QUESTION: Is personalized-dose corticosteroid administered according to a dosing scale more effective than fixed-dose corticosteroid administration in hospitalized patients with COPD with exacerbations? STUDY DESIGN AND METHODS: This was a prospective, randomized, open-label trial. In-hospital patients with COPD with exacerbations were randomly assigned at a 1:1 ratio to either the fixed-dose group (receiving the equivalent of 40 mg of prednisolone) or the personalized-dose group for 5 days. The primary end point was a composite measure of treatment failure that included in-hospital treatment failure and medium-term (postdischarge) failure. Secondary end points were length of stay and cost. RESULTS: A total of 248 patients were randomly assigned to the fixed-dose group (n = 124) or personalized-dose group (n = 124). One patient in each group was not included in the intention-to-treat population because of incorrect initial COPD diagnosis. Failure of therapy occurred in 27.6% in the personalized-dose group, compared with 48.8% in the fixed-dose group (relative risk, 0.40; 95% CI, 0.24-0.68; P = .001). The in-hospital failure of therapy was significantly lower in the personalized-dose group (10.6% vs 24.4%; P = .005), whereas the medium-term failure rate, adverse event rate, hospital length of stay, and costs were similar between the two groups. After treatment failure, a lower additional dose of corticosteroids and a shorter duration of treatment were needed in the personalized-dose group to achieve control of the exacerbation. In the personalized-dose cohort, those receiving 40 mg or less had an average failure rate of 44.4%, compared with 22.9% among those receiving more than 40 mg (P = .027). INTERPRETATION: Personalized dosing of corticosteroids reduces the risk of failure because more patients were provided with a higher initial dose, especially > 60 mg, whereas 40 mg or less was too low in either group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02147015; URL: www.clinicaltrials.gov.

Asunto(s)

Relación Dosis-Respuesta a Droga , Glucocorticoides , Enfermedad Pulmonar Obstructiva Crónica , Administración por Inhalación , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Anciano , Cálculo de Dosificación de Drogas , Femenino , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Readmisión del Paciente/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/terapia , Evaluación de Síntomas/métodos , Brote de los Síntomas

RESUMEN

Recently, COVID-19 caused by the novel coronavirus SARS-CoV-2 has brought great challenges to the world. More and more studies have shown that patients with severe COVID-19 may suffer from cytokine storm syndrome; however, there are few studies on its pathogenesis. Here we demonstrated that SARS-CoV-2 coding protein open reading frame 8 (ORF8) acted as a contributing factor to cytokine storm during COVID-19 infection. ORF8 could activate IL-17 signaling pathway and promote the expression of pro-inflammatory factors. Moreover, we demonstrated that treatment of IL17RA antibody protected mice from ORF8-induced inflammation. Our findings are helpful to understand the pathogenesis of cytokine storm caused by SARS-CoV-2 and provide a potential target for the development of COVID-19 therapeutic drugs.