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Background: The hemoglobin-albumin-lymphocyte-platelet (HALP) index is a novel biomarker reflecting systemic inflammation and nutritional status which are important for coronavirus disease 2019 (COVID-19) mortality. However, the association between HALP and mortality in patients with COVID-19 has yet to be investigated. Methods: A cohort of COVID-19 Omicron BA.2 infected patients admitted to the Shanghai Fourth People's Hospital, School of Medicine, Tongji University from April 12, 2022 to June 17, 2022 was retrospectively analyzed. Laboratory examinations on hospital admission, including hemoglobin, albumin, and lymphocyte and platelet, were collected. The association between baseline HALP and in-hospital poor overall survival (OS) was assessed using Kaplan-Meier curves, Cox regression models, interaction, and stratified analyses. Results: A total of 2147 patients with COVID-19 Omicron BA.2 infection were included in the final analyses, and mortality in the hospital was 2.65%. Multivariate analysis indicated that low HALP index was independently associated with in-hospital mortality of COVID-19 patients [hazard ratio (HR) = 2.08; 95% confidence interval (CI) = 1.17-3.73]. Subgroup analysis demonstrated that low HALP index was an independent risk factor for in-hospital mortality in COVID-19 patients with age ≥70 (HR = 2.22, CI = 1.18-4.15) and severe cases (HR = 2.09, CI = 1.13-3.86). Conclusion: HALP index is independently related to in-hospital poor OS for COVID-19 Omicron BA.2 infected patients, especially for age ≥70 and severe cases. HALP index on hospital admission is a useful candidate biomarker for identifying high risk of mortality in COVID-19 Omicron BA.2 infected patients.
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Purpose: This study aims to investigate the relationship between the total muscle-to-fat ratio (tMFR) and female urinary incontinence (UI), determine whether tMFR can serve as a useful index for predicting UI, and identify factors that may influence this relationship. Methods: We retrospectively analyzed data from 4391 adult women participating in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. The correlation between tMFR and UI was examined using a dose-response curve generated through a restricted cubic spline (RCS) function, LASSO and multivariate logistic regression. Furthermore, predictive models were constructed incorporating factors such as age, race, hypertension, diabetes, cotinine levels, and tMFR. The performance of these predictive models was evaluated using training and test datasets, employing calibration curves, receiver operating characteristic curves, and clinical decision curves. Mediation effects were also analyzed to explore potential relationships between tMFR and female UI. Results: In a sample of 4391 adult women, 1073 (24.4%) self-reported experiencing UI, while 3318 (75.6%) reported not having UI. Based on the analyses involving LASSO regression and multivariate logistic regression, it was found that tMFR exhibited a negative association with UI (OR = 0.599, 95% CI: 0.497-0.719, P < 0.001). The results from the restricted cubic spline chart indicated a decreasing risk of UI in women as tMFR increased. Furthermore, the model constructed based on logistic regression analysis demonstrated a certain level of accuracy (in the training dataset: area under the curve (AUC) = 0.663; in the test dataset: AUC = 0.662) and clinical applicability. The mediation analysis revealed that the influence of tMFR on the occurrence of UI in women might potentially occur through the blood index lymphocyte count (P = 0.040). Conclusion: A high tMFR serves as a protective factor against UI in women. Furthermore, lymphocyte might be involved in the relationship between tMFR and female UI.
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Incontinência Urinária , Adulto , Humanos , Feminino , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Estudos Retrospectivos , Incontinência Urinária/diagnóstico , Incontinência Urinária/epidemiologia , Músculos , Curva ROCRESUMO
BACKGROUND: Postoperative delirium, particularly prevalent in elderly patients after abdominal cancer surgery, presents significant challenges in clinical management. AIM: To develop a synthetic minority oversampling technique (SMOTE)-based model for predicting postoperative delirium in elderly abdominal cancer patients. METHODS: In this retrospective cohort study, we analyzed data from 611 elderly patients who underwent abdominal malignant tumor surgery at our hospital between September 2020 and October 2022. The incidence of postoperative delirium was recorded for 7 d post-surgery. Patients were divided into delirium and non-delirium groups based on the occurrence of postoperative delirium or not. A multivariate logistic regression model was used to identify risk factors and develop a predictive model for postoperative delirium. The SMOTE technique was applied to enhance the model by oversampling the delirium cases. The model's predictive accuracy was then validated. RESULTS: In our study involving 611 elderly patients with abdominal malignant tumors, multivariate logistic regression analysis identified significant risk factors for postoperative delirium. These included the Charlson comorbidity index, American Society of Anesthesiologists classification, history of cerebrovascular disease, surgical duration, perioperative blood transfusion, and postoperative pain score. The incidence rate of postoperative delirium in our study was 22.91%. The original predictive model (P1) exhibited an area under the receiver operating characteristic curve of 0.862. In comparison, the SMOTE-based logistic early warning model (P2), which utilized the SMOTE oversampling algorithm, showed a slightly lower but comparable area under the curve of 0.856, suggesting no significant difference in performance between the two predictive approaches. CONCLUSION: This study confirms that the SMOTE-enhanced predictive model for postoperative delirium in elderly abdominal tumor patients shows performance equivalent to that of traditional methods, effectively addressing data imbalance.
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PURPOSE: Heavy metal exposure can cause impaired or reduced pathology in the kidneys, lungs, liver, and other vital organs. However, the relationship between heavy metal exposure and kidney stones has not been determined. The goal of this research was to determine the association between heavy metal exposure and kidney stones in a population of American adults in general. MATERIALS AND METHODS: We evaluated 29,201 individuals (≥20 years) from the National Health and Nutrition Examination Survey (NHANES). The association between heavy metal exposure and kidney stones was verified by multiple logistic regression and restricted cubic spline (RCS) regression. Dose-response curves were generated to analyze the relationship between heavy metal concentrations and the occurrence of kidney stones. Moreover, we used propensity score matching (PSM) to exclude the effect of confounding variables. RESULTS: After a rigorous enrollment screening process, we included 8518 participants. Logistic regression showed that urinary cadmium (U-Cd) and urinary cobalt (U-Co) concentrations were significantly different in the kidney stone group before PSM (p < 0.001). Dose-response curves revealed that the occurrence of kidney stones increased significantly with increasing U-Cd and U-Co concentrations. After adjustment for covariates, only biomarkers of U-Co were linked to the occurrence of kidney stones. When the lowest quartile was used as a reference, the 95% confidence intervals (95% CIs) for kidney stones across the other quartiles were 1.015 (0.767-1.344), 1.409 (1.059-1.875), and 2.013 (1.505-2.693) for U-Cos (p < 0.001). CONCLUSION: In the U.S. population, high U-Co levels are positively correlated with the potential risk of kidney stones.
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Cobalto , Cálculos Renais , Adulto , Humanos , Inquéritos Nutricionais , Cádmio , Cálculos Renais/induzido quimicamente , Cálculos Renais/epidemiologia , RimRESUMO
Anti-interleukin-17 (IL-17) therapy has been used in various autoimmune diseases. However, the efficacy is unexpectedly limited in several IL-17-associated diseases, and the mechanism of limited efficacy remains unclear. Here, we show that a molecular complex containing the adaptor molecule Act1 and tyrosine phosphatase SHP2 mediated autonomous IL-17R signaling that accelerated and sustained inflammation. SHP2, aberrantly augmented in various autoimmune diseases, was induced by IL-17A itself in astrocytes and keratinocytes, sustaining chemokine production even upon anti-IL-17 therapies. Mechanistically, SHP2 directly interacted with and dephosphorylated Act1, which replaced Act1-TRAF5 complexes and induced IL-17-independent activation of IL-17R signaling. Genetic or pharmacologic inactivation of SHP2, or blocking Act1-SHP2 interaction, paralyzed both IL-17-induced and IL-17-independent signaling and attenuated primary or relapsing experimental autoimmune encephalomyelitis. Therefore, Act1-SHP2 complexes mediate an alternative pathway for autonomous activation of IL-17R signaling, targeting which could be a therapeutic option for IL-17-related diseases in addition to current antibody therapies.
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Encefalomielite Autoimune Experimental , Receptores de Interleucina-17 , Animais , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Inflamação , Progressão da DoençaRESUMO
Objective: To construct and validate nomogram models that predict the incidence of delirium in elderly patients with non-severe SARS-CoV-2 infection. Methods: Elderly patients (≥65y) tested positive for SARS-CoV-2 infection at the hospital were included. We used the 3-min diagnostic Confusion Assessment Method for delirium diagnosis. Least absolute shrinkage and selection operator (LASSO) logistical regression analysis was performed to explore potential independent influencing factors of delirium. A predict model visualized by nomogram was constructed based on the confirmed variables. The predictive accuracy and clinical value of the model were evaluated using receiver operating characteristic (ROC) curves. Results: The data of 311 elderly patients were analyzed, of whom 73 (23.47%) patients were diagnosed with delirium. Three independent influencing factors of delirium were confirmed: age (OR1.16,1.11-1.22), Glomerular filtration rate (OR 0.98,0.97-0.99), platelet-large cell ratio (1.06,1.02-1.10). These parameters were used to create a nomogram to predict the development of delirium, which showed good predictive accuracy confirmed by the ROC curves (AUC 0.82,0.76-0.88). Conclusion: We construct a credible nomogram to predict the development of delirium in elderly patients with Non-severe SARS-CoV-2 infection. Our finding may be useful to physicians in early prevention and treatment of delirium.
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Cisplatin and other platinum-based drugs are used frequently for treatment of lung cancer. However, their clinical performance are usually limited by drug resistance or toxic effects. Carnosic acid, a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), has been reported to have several pharmacological and biological activities. In the present study, the combination effect of cisplatin plus carnosic acid on mouse LLC (Lewis lung cancer) xenografts and possible underlying mechanism of action were examined. LLC-bearing mice were treated with intraperitoneal injection with cisplatin, oral gavage with carnosic acid, or combination with cisplatin and carnosic acid, respectively. Combination of carnosic acid and cisplatin yielded significantly better anti-growth and pro-apoptotic effects on LLC xenografts than drugs alone. Mechanistic study showed that carnosic acid treatment boosted the function of CD8+ T cells as evidenced by higher IFN-γ secretion and higher expression of FasL, perforin as well as granzyme B. In the meantime, the proportion of MDSC (myeloid-derived suppressor cells) in tumor tissues were reduced by carnosic acid treatment and the mRNA levels of iNOS2, Arg-1, and MMP9, which are the functional markers for MDSC, were reduced. In conclusion, our study proved that the functional suppression of MDSC by carnosic acid promoted the lethality of CD8+ T cells, which contributed to the enhancement of anti-lung cancer effect of cisplatin.
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Abietanos/administração & dosagem , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Células Supressoras Mieloides/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Rosmarinus/química , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/imunologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Interferon gama/genética , Interferon gama/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/imunologiaRESUMO
An investigation of relaxed alignment tolerance in monolithic ring lasers is presented. It was found that the relaxed alignment tolerance is strongly dependent on the out-of-plane angle. A preferred region for the out-of-plane angle is proposed. In this region the resonator has greatly relaxed alignment tolerances, and the unidirectional operation can be obtained under a much-lower magnetic field. Two lasers have been constructed in the region, and satisfactory performance was found, in good agreement with the theoretical analysis.