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Breath metabolomics for diagnosis of acute respiratory distress syndrome.
Zhang, S, Hagens, LA, Heijnen, NFL, Smit, MR, Brinkman, P, Fenn, D, van der Poll, T, Schultz, MJ, Bergmans, DCJJ, Schnabel, RM, et al
Critical care (London, England). 2024;(1):96
Abstract
BACKGROUND Acute respiratory distress syndrome (ARDS) poses challenges in early identification. Exhaled breath contains metabolites reflective of pulmonary inflammation. AIM: To evaluate the diagnostic accuracy of breath metabolites for ARDS in invasively ventilated intensive care unit (ICU) patients. METHODS This two-center observational study included critically ill patients receiving invasive ventilation. Gas chromatography and mass spectrometry (GC-MS) was used to quantify the exhaled metabolites. The Berlin definition of ARDS was assessed by three experts to categorize all patients into "certain ARDS", "certain no ARDS" and "uncertain ARDS" groups. The patients with "certain" labels from one hospital formed the derivation cohort used to train a classifier built based on the five most significant breath metabolites. The diagnostic accuracy of the classifier was assessed in all patients from the second hospital and combined with the lung injury prediction score (LIPS). RESULTS A total of 499 patients were included in this study. Three hundred fifty-seven patients were included in the derivation cohort (60 with certain ARDS; 17%), and 142 patients in the validation cohort (47 with certain ARDS; 33%). The metabolites 1-methylpyrrole, 1,3,5-trifluorobenzene, methoxyacetic acid, 2-methylfuran and 2-methyl-1-propanol were included in the classifier. The classifier had an area under the receiver operating characteristics curve (AUROCC) of 0.71 (CI 0.63-0.78) in the derivation cohort and 0.63 (CI 0.52-0.74) in the validation cohort. Combining the breath test with the LIPS does not significantly enhance the diagnostic performance. CONCLUSION An exhaled breath metabolomics-based classifier has moderate diagnostic accuracy for ARDS but was not sufficiently accurate for clinical use, even after combination with a clinical prediction score.
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Global burden and risk factors of gastritis and duodenitis: an observational trend study from 1990 to 2019.
Liu, Y, Zhang, J, Guo, Y, Tian, S, Wu, Y, Liu, C, Huang, X, Zhang, S, Dong, W
Scientific reports. 2024;(1):2697
Abstract
In recent years, there has been a global trend of aging, which has resulted in significant changes to the burden of gastritis and duodenitis (GD). Using the global burden of disease (GBD) database spanning 1990 to 2019, we evaluated the temporal trends of age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and age-standardized disability-adjusted life years (AS-DALYs) for GD using estimated annual percentage changes (EAPC). Additionally, we examined the burden of GD across various strata, including social demographic index (SDI), age, and sex. Finally, the risk factors linked to the incidence and mortality of GD, utilizing Pearson correlation analysis. In 2019, there were 31 million GD patients globally, a notable increase of 12 million from 1990, while the ASIR, ASDR, and AS-DALYs for GD all showed a decrease. Correlation analysis showed a significant negative relationship between ASIR and SDI. Factors like hand hygiene and vitamin A deficiency had significant positive correlations with ASIR and ASDR in 2019. Over the past thirty years, the burden of GD has increased alongside global population aging. Future efforts should focus on exploring prevention for GD, with special attention to the elderly population in low SDI regions.
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Modifiable risk factors for ventilator associated diaphragmatic dysfunction: a multicenter observational study.
Pu, H, Doig, GS, Lv, Y, Wu, X, Yang, F, Zhang, S, Liang, Z, Zhou, Y, Kang, Y
BMC pulmonary medicine. 2023;(1):343
Abstract
BACKGROUND Diaphragmatic dysfunction is known to be associated with difficulties weaning from invasive mechanical ventilation and is related to worse patient outcomes yet our understanding of how to prevent diaphragmatic dysfunction remains incomplete. We examined potentially modifiable risk factors for diaphragmatic dysfunction and attempted to estimate benefits attributable to altering these modifiable risk factors. METHODS This prospective multicenter observational study was undertaken in the general ICUs of two tertiary care teaching hospitals. Critically ill adults expected to receive invasive mechanical ventilation for at least 48 h were enrolled. Diaphragm function was assessed by ultrasound each study day, with dysfunction defined as thickening fraction less than 20%. RESULTS From January to December 2019, 856 patients were screened and 126 patients were enrolled. Overall, 40.5% (51/126) of patients experienced diaphragmatic dysfunction during invasive mechanical ventilation. Patients with diaphragmatic dysfunction were more likely to develop ventilator associated pneumonia (risk difference [RD] + 12.9%, 95% Confidence Interval [CI] 1.4 to 24.4%, P = 0.028), were more likely to experience extubation failure (RD + 8.5%, 95% CI 0.4 to 16.6%, P = 0.039) and required a longer duration of invasive mechanical ventilation (RD + 1.3 days, 95% CI 0.1 to 2.5 days, P = 0.035). They also required a longer hospital stay (RD + 1.2 days, 95% CI 0.04 to 2.4 days, P = 0.041) and were more likely to die before hospital discharge (RD + 18.1%, 95% CI 3.7 to 32.5%, P = 0.014). Multivariable analysis considered the impact of age, sex, pre-existing nutritional status, caloric intake, amino acid intake, acute disease severity, modes of mechanical ventilation, measures of respiratory status, sedation, pain control and baseline diaphragm thickness. Only SOFA score (P = 0.008) and early amino acid intake (P = 0.001) remained significant independent risk factors for the onset of diaphragmatic dysfunction. Causal path modeling suggested early amino acid intake may significantly reduce diaphragmatic dysfunction (RRR 29%, 95% CI 10% to 48%, P = 0.003) and may also reduce mortality (RRR 49%, 95% CI 25% to 73%, P < 0.0001). CONCLUSIONS Amino acid intake during the first 24 h of ICU stay may represent an important, modifiable risk factor for diaphragmatic dysfunction and may have a direct causal effect on mortality. We recommend additional research on this topic.
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Body Composition-Specific Asthma Phenotypes: Clinical Implications.
Zhang, X, Deng, K, Yuan, Y, Liu, L, Zhang, S, Wang, C, Wang, G, Zhang, H, Wang, L, Cheng, G, et al
Nutrients. 2022;(12)
Abstract
BACKGROUND Previous studies have indicated the limitations of body mass index for defining disease phenotypes. The description of asthma phenotypes based on body composition (BC) has not been largely reported. OBJECTIVE To identify and characterize phenotypes based on BC parameters in patients with asthma. METHODS A study with two prospective observational cohorts analyzing adult patients with stable asthma (n = 541 for training and n = 179 for validation) was conducted. A body composition analysis was performed for the included patients. A cluster analysis was conducted by applying a 2-step process with stepwise discriminant analysis. Logistic regression models were used to evaluate the association between identified phenotypes and asthma exacerbations (AEs). The same algorithm for cluster analysis in the independent validation set was used to perform an external validation. RESULTS Three clusters had significantly different characteristics associated with asthma outcomes. An external validation identified the similarity of the participants in training and the validation set. In the training set, cluster Training (T) 1 (29.4%) was "patients with undernutrition", cluster T2 (18.9%) was "intermediate level of nutrition with psychological dysfunction", and cluster T3 (51.8%) was "patients with good nutrition". Cluster T3 had a decreased risk of moderate-to-severe and severe AEs in the following year compared with the other two clusters. The most important BC-specific factors contributing to being accurately assigned to one of these three clusters were skeletal muscle mass and visceral fat area. CONCLUSION We defined three distinct clusters of asthma patients, which had distinct clinical features and asthma outcomes. Our data reinforced the importance of evaluating BC to determining nutritional status in clinical practice.
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The AST/ALT Ratio (De Ritis Ratio) Represents an Unfavorable Prognosis in Patients in Early-Stage SFTS: An Observational Cohort Study.
Wang, L, Xu, Y, Zhang, S, Bibi, A, Xu, Y, Li, T
Frontiers in cellular and infection microbiology. 2022;:725642
Abstract
BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS), a widely prevalent infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) that carries with it a high mortality rate, has emerged to be a public health concern. This study aimed to investigate the epidemiological and clinical characteristics of patients infected with SFTSV, seeking novel prognostic risk factors for SFTS. METHODS In this retrospective and cross-sectional study, confirmed SFTS patients from the First Affiliated Hospital of Anhui Medical University were enrolled from September 1, 2019, to December 12, 2020. Cases were analyzed for epidemiological, demographic, clinical, and laboratory data. Logistic regression models were used to assess the association between predictors and outcome variables. A generalized additive mixed model (GAMM) was conducted to analyze the trending shift of aspartate aminotransferase/alanine transaminase-ratio (AST/ALT-ratio) and platelet (PLT) in SFTS patients treated with ribavirin. p values ≤ 0.05 were considered statistically significant. RESULTS Clinical and laboratory results of 107 hospitalized patients with SFTSV infection were retrospectively described. The mean age at onset of disease was 60.38 ± 11.29 years old and the ratio between male and female was 1:1.2. Fever and thrombocytopenia are hallmark features of SFTS. Furthermore, multiple cases also experienced neurological complications, gastrointestinal/skeletal muscle symptoms together with other non-specific clinical manifestations; laboratory dataset outcomes reported dysregulated levels for routine blood biomarkers, coagulation function, and biochemistry. Overall, 107 patients were segregated into two groups according to patient condition at the clinical endpoint (survivors/non-survivors). SFTS survivors had a higher level of PLT- counts, total protein (TP), and estimated glomerular filtration rate (eGFR), while levels of activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (D-D), fibrinogen degradation products (FDP), ALT, AST, AST/ALT-ratio, creatinine (Cr), creatine phosphokinase (CK) and procalcitonin (PCT) was higher in non-survivors. Results from univariate Cox regression revealed that elevated levels of FDP, TT, AST/ALT-ratio, PCT, as well as decreased eGFR level and presence of central nervous system symptoms (CNS), were significant predictors for SFTS prognostic, results from multivariate logistic regression analysis in three adjusted models showed AST/ALT-ratio and PCT were independent risk factors for the prognosis of SFTS patients. Kaplan-Meier survival analysis showed that SFTS patients with AST/ALT-ratio >2.683 were associated with a shorter futime (means survival time), therefore indicating an unfavorable prognosis. Treatment with ribavirin could increase PLT count while decreasing AST/ALT-ratio within SFTS patients. CONCLUSION SFTS is an emerging infectious disease, possibly leading to multiple-organ injury; AST/ALT-ratio was an independent risk factor for the prognosis of SFTS patients. Further investigation should be performed in order to gain more knowledge on this disease and guide clinical management.
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Sex-specific mediating effect of gestational weight gain between pre-pregnancy body mass index and gestational diabetes mellitus.
Zhang, S, Wang, J, Xu, F, Yang, J, Qin, Y, Leng, J, Li, N, Guo, J, Li, X, Gao, Z, et al
Nutrition & diabetes. 2022;(1):25
Abstract
BACKGROUND Inappropriate weight gain may increase the risk of gestational diabetes mellitus (GDM). However, the relationship between pre-pregnancy body mass index (BMI), weight gain, and GDM has not been precisely quantified. This study aimed to explore whether gestational weight gain played a mediating role between pre-pregnancy BMI and GDM and whether the mediating effect was sex specific. METHODS This study established a population-based observational cohort to assess weight gain in pregnant women. Mediation analyses were performed to quantify whether weight gain mediated the association between pre-pregnancy BMI and GDM. RESULTS A total of 67,777 pregnant women were included in the final analysis, among whom 6751 (10.0%) were diagnosed with GDM. We verified that both pre-pregnancy BMI and weight gain were associated with GDM, and that BMI negatively contributed to weight gain. We also found that weight gain had a significant mediating effect on the relationship between pre-pregnancy BMI and GDM (Za × Zb confidence intervals [CIs] 0.00234-0.00618). Furthermore, the effect was sex-specific, in that it was only significant in overweight women carrying female fetuses (Za × Zb CIs 0.00422-0.01977), but not male fetuses (Za × Zb CIs -0.00085 to 0.01236). CONCLUSIONS Weight gain during pregnancy had a fetal sex-specific mediating effect between pre-pregnancy BMI and GDM.
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7.
Role of hsa‑miR‑105 during the pathogenesis of paclitaxel resistance and its clinical implication in ovarian cancer.
Li, M, Zhang, S, Ma, Y, Yang, Y, An, R
Oncology reports. 2021;(5)
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Abstract
More than 70% of patients with epithelial ovarian cancer (EOC), one of the leading cause of gynecological cancer‑related deaths worldwide, are diagnosed at an advanced stage of the disease. Currently, the mainstay for treatment of advanced EOC is tumor debulking surgery followed by combined platinum‑ and paclitaxel (PTX)‑based chemotherapy. However, most patients eventually develop chemoresistance, which remains a major obstacle to successful treatment. Herein, by using clinical specimens and experimentally induced cell models, we found that the expression levels of hsa‑miR‑105 were significantly decreased in PTX‑resistant EOC tissues and cell lines. Follow‑up functional experiments demonstrated that repression of hsa‑miR‑105 conferred resistance to paclitaxel in EOC cells, whereas restoration of hsa‑miR‑105 expression in situ via intratumoral injection of hsa‑miR‑105 micrON™ agomir potentiated in vivo sensitivity to PTX and thereafter significantly inhibited tumor growth in a PTX‑challenged xenograft model. Mechanistically, hsa‑miR‑105 exerted its tumor suppressor function by directly inhibiting the zinc and ring finger 2 (ZNRF2) signaling pathway. Importantly, aberrant expression of hsa‑miR‑105 in both tumor and circulating samples predicted a poor post‑chemotherapy prognosis in EOC patients. These findings collectively suggest that hsa‑miR‑105 may act as a potent tumor suppressor miRNA during the progression of EOC, likely affecting cell proliferation, invasiveness and chemosensitivity to PTX, and functioning at least in part via inhibition of ZNRF2 signaling. The stability and availability and ease in measurement of circulating hsa‑miR‑105 make it a valuable diagnostic/prognostic biomarker candidate for chemotherapy of EOC.
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Elevated glucose level leads to rapid COVID-19 progression and high fatality.
Wang, W, Shen, M, Tao, Y, Fairley, CK, Zhong, Q, Li, Z, Chen, H, Ong, JJ, Zhang, D, Zhang, K, et al
BMC pulmonary medicine. 2021;(1):64
Abstract
OBJECTIVES We aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients. METHODS We enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality. RESULTS The median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8-5.5), 3.0 (1.0-7.0), 3.0 (1.0-8.0), and 6.5 (4.0-16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19. CONCLUSIONS Older age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.
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Association among emotional and behavioural problems, sexual minority status and suicidal behaviours in adolescents: a cross-sectional study from Guangdong Province in China.
Li, W, Guo, L, Zhang, S, Wang, W, Chen, X, Li, Q, Lu, C
BMJ open. 2021;(9):e051485
Abstract
OBJECTIVES This study was conducted to estimate whether emotional and behavioural problems mediate the association between sexual minority status and suicidal behaviour among Chinese adolescents. We also tested whether such mediation is moderated by the sex assigned at birth. DESIGN Cross-sectional observational study. SETTING A secondary analysis of the cross-sectional data collected from 7th-grade to 12th-grade students in junior high schools (n=36), senior high schools (n=24) and vocational high schools (n=12) in six cities of Guangdong Province, China. A multistage, stratified cluster, random sampling method was used in the 2019 School-based Chinese Adolescents Health Survey. PARTICIPANTS A total of 16 663 students aged 11-20 years. OUTCOME MEASURES Two main psychological and mental health outcomes: (1) self-reported version of the Strengths and Difficulties Questionnaire to measure emotional and behavioural problems; and (2) presence of suicidal ideation and suicide attempts in the past 12 months. RESULTS Emotional and behavioural problems (peer problems, emotional problems, conduct problems and hyperactivity) partially mediated the effects of sexual minority status on suicidal ideation (indirect effect=0.020, 95% CI 0.015 to 0.025) and suicide attempts (indirect effect=0.012, 95% CI 0.009 to 0.016), accounting for 18.18% and 14.46% of the total effect, respectively. Further moderated mediation analyses revealed a greater risk of suicidality among sexual minority girls. CONCLUSIONS Emotional and behavioural problems partially explained the increased risk of suicidality among sexual minority adolescents, and appreciably higher among sexual minority girls than boys. To prevent subsequent suicidality, the risks of emotional and behavioural problems in sexual minority adolescents should be identified at an early stage and reduced by means of preventive measures.
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Vitamin B6 as a novel risk biomarker of fractured ankles.
Li, Z, Zhang, S, Wan, L, Song, X, Yuan, D, Zhang, S, Wu, D, Jiang, J
Medicine. 2021;(40):e27442
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Abstract
Ankle fractures are the most common intra-articular fractures. Osteoporosis is a common and frequent disease among the elderly with a poor prognosis and high risk of fractured ankles. However, the relationship between vitamin B6 and the incidence of fractured ankles in patients with osteoporosis is unclear.A total of 101 patients with osteoporosis were recruited. Clinical and followed-up information was recorded. And the vitamin B6, albumin, globulin, and hemoglobin in the blood were tested. Pearson's chi-squared and spearman test were performed to analyze the correlation between fractured ankles and relative parameters. Univariate and multivariate logistic regression, receiver operating characteristic curve analysis, univariate and multivariate Cox proportional hazards regression analysis, and Kaplan-Meier method were also performed.There exist strong relation between the expression level of vitamin B6 and fractured ankle (P < .001). The expression of vitamin B6 [Odd ratio (OR) = 12.071, 95% confidence interval (CI): 4.69-31.143, P < .001] has a clear correlation with whether the patients have fractured ankles via the univariate logistic regression analysis. In terms of multivariate logistic regression level, vitamin B6 (OR = 15.384, 95% CI:5.195-45.556, P < .001) was significantly associated with fractured ankle. In addition, expression level of vitamin B6 [hazard ratio (HR) = 11.684, 95% CI: 6.419-21.267, P < .001] was significantly associated with Maintenance time from recovery to recurrence (MRTT) of patients with osteoporosis.Enhanced vitamin B6 is significantly correlated with the poor prognosis of patients with osteoporosis and the increasing incidence of fractured ankles.