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Background: Alterations gastrointestinal diseases (GDs) were reported in individuals with obstructive sleep apnea (OSA), however, the genetic background between OSA and GDs is still unclear. Methods: This investigation employed Mendelian randomization (MR) analyses to evaluate the causal effect between OSA and 19 types of GDs (gastroesophageal reflux disease (GERD), ulcerative colitis, celiac disease, Crohn's disease, chronic gastritis, irritable bowel syndrome, primary biliary cholangitis, diverticular disease, gastroduodenal ulcer, acute pancreatitis, non-alcoholic fatty liver disease, primary sclerosing cholangitis, cirrhosis, calculus of bile duct, calculus of gallbladder, pancreatic cancer, gastric cancer, colorectal cancer, and esophageal cancer). The inverse-variance weighted (IVW) method was used to evaluate the main effects model of causality. Results: This MR study suggests that OSA may play a causal role inflammation-related GDs (GERD, PIVW=5.94×10-9; gastroduodenal ulcer, PIVW=1×10-4; chronic gastritis, PIVW=0.0214; ulcerative colitis, PIVW=0.0296), and gallstones (calculi of the gallbladder, PIVW=0.0429; calculi of the bile duct, PIVW=0.0068). After accounting for obesity, type 2 diabetes, smoking, and alcohol consumption, the multivariate MR (MVMR) analysis identified that OSA is an independent risk factor for GERD, gastroduodenal ulcer, and calculus of the bile duct. The reverse MVMR analysis showed a causal effect of GERD on OSA. Besides, we did not find that the predisposition to OSA was associated with 4 cancers. Conclusion: This MR analysis provides compelling evidence of an independent causal relationship between genetically predicted OSA and an elevated risk of inflammation-related GDs. Besides, no causal association was observed between OSA and cancers. Further studies should be carried out to verify our findings.
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The objective of this study is to explore the associations between obesity, body composition, and the self-reported risk of obstructive sleep apnea (OSA) and to examine whether the risk of OSA is related to metabolic abnormalities in children and adolescents aged 6-17 years. Utilizing data from the 2022 to 2023 Beijing Children and Adolescents Health Cohort baseline survey, 5000 school-aged participants were analyzed. OSA risk was assessed via the Pediatric Sleep Questionnaire, with anthropometric and body composition measurements taken. Metabolic markers included blood pressure, lipid levels, blood glucose, and uric acid. Associations were analyzed using logistic regression and generalized linear models. Results showed that 88.6% were low-risk and 11.4% were high-risk for OSA. Overweight (aOR 1.53, 95% CI 1.22-1.92), obesity (aOR 1.94, 95% CI 1.57-2.40), and abdominal obesity (aOR 1.59, 95% CI 1.31-1.93) significantly increased OSA risk. High fat mass was a critical factor, while muscle mass was not, especially in those who were overweight and obese. Associations of OSA risk with metabolic abnormalities were non-significant after adjusting for BMI. Our research highlights the significant associations of obesity and body composition with OSA risk, with child BMI influencing the relationship between OSA and metabolic abnormalities. Future research should explore causative relationships and the enduring impacts of OSA on metabolic health in children.
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Composição Corporal , Obesidade Infantil , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Adolescente , Masculino , Feminino , Criança , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Fatores de Risco , Índice de Massa Corporal , Estudos de Coortes , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologiaRESUMO
OBJECTIVES: To investigate the efficacy and safety of carbon dioxide (CO2) laser cauterization in the treatment of pediatric congenital pyriform sinus fistula (CPSF), and to track and follow up the long-term outcome of the postoperative patients. METHODS: This retrospective study was conducted at a single center, where clinical data and follow-up information of children with CPSF who underwent CO2 laser cauterization with the assistance of a suspension laryngoscope and microscope were collected and analyzed their clinical characteristics and prognosis. Subsequently, multiple logistic regression analysis was performed to identify potential predictors of the number of laser cauterization procedures. RESULTS: A total of 238 children diagnosed with CPSF were recruited for this study, with 235 patients successfully achieving closure of the internal fistula through one or more CO2 laser cauterization procedures without recurrence. The median duration of follow-up was 6.46 (5.20, 7.64) years. Merely three patients (1.3%) developed recurrent cervical infection and eventually underwent open neck surgery. There were no instances of permanent perioperative complications throughout the follow-up. Additionally, our analysis revealed that the age at the first operation of CO2 laser cauterization was an independent risk factor associated with the number of operations. CONCLUSIONS: The CO2 laser cauterization for children with CPSF is an effective and safe treatment with a low recurrence rate and minimal complications during the follow-up period. Consequently, it is advisable to consider CO2 laser cauterization as a viable therapeutic option for managing pediatric CPSF. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.
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Varicocele (VC) refers to expansion and tortuosity of spreading venous plexus in spermatic cord due to poor blood flow. This study aimed to investigate effects of Shugan Tongluo Qiangjing recipe (SGTL) on sperm DNA damage and oxidative stress in experimental VC (EVC) rats. EVC model was established by partial ligation of left renal vein. Spermatic vein diameter, testicular weight, sperm DNA fragmentation index (DFI) were evaluated. Telomere reverse transcriptase (TERT) expression, telomere gene transcription, and testicular tissue morphology were determined·H2O2, catalase, SOD, T-AOC were measured with colorimetry. SGTL significantly decreased spermatic vein diameter (P=0.000) and increased testicular weight (P=0.013) of rats compared those of EVC rats. SGTL maintained testicular tissue morphology in EVC rats. SGTL markedly reduced sperm DFI value in sperm of rats compared to EVC rats (P=0.000). SGTL significantly enhanced TERT expression and telomere gene transcription (P=0.028) in testis of rats compared to EVC rats. SGTL reduced H2O2 levels (P=0.001) and promoted CAT activity (P=0.016), SOD activity (P=0.049), and T-AOC activity (P=0.047) of rats, compared to EVC rats. In conclusion, SGTL could reduce pathogenic process of EVC by reducing sperm DNA damage and regulating telomere length in EVC rats, which may be related to oxidative stress regulation.
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Dano ao DNA , Medicamentos de Ervas Chinesas , Estresse Oxidativo , Espermatozoides , Telômero , Varicocele , Animais , Masculino , Estresse Oxidativo/efeitos dos fármacos , Varicocele/patologia , Varicocele/metabolismo , Telômero/efeitos dos fármacos , Telômero/metabolismo , Dano ao DNA/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Testículo/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia , Ratos Sprague-DawleyRESUMO
Objective: The objective of this study was to investigate the effectiveness of a machine learning algorithm in diagnosing OSA in children based on clinical features that can be obtained in nonnocturnal and nonmedical environments. Patients and methods: This study was conducted at Beijing Children's Hospital from April 2018 to October 2019. The participants in this study were 2464 children aged 3-18 suspected of having OSA who underwent clinical data collection and polysomnography(PSG). Participants' data were randomly divided into a training set and a testing set at a ratio of 8:2. The elastic net algorithm was used for feature selection to simplify the model. Stratified 10-fold cross-validation was repeated five times to ensure the robustness of the results. Results: Feature selection using Elastic Net resulted in 47 features for AHI ≥5 and 31 features for AHI ≥10 being retained. The machine learning model using these selected features achieved an average AUC of 0.73 for AHI ≥5 and 0.78 for AHI ≥10 when tested externally, outperforming models based on PSG questionnaire features. Linear Discriminant Analysis using the selected features identified OSA with a sensitivity of 44% and specificity of 90%, providing a feasible clinical alternative to PSG for stratifying OSA severity. Conclusions: This study shows that a machine learning model based on children's clinical features effectively identifies OSA in children. Establishing a machine learning screening model based on the clinical features of the target population may be a feasible clinical alternative to nocturnal OSA sleep diagnosis.
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Kelp, the brown alga distributed in coastal areas all over the world, is also an important medicine food homology product in China. However, the levels and profiles of persistent organic pollutants (POPs) in kelp have not been thoroughly investigated to date. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and emerging bromine flame retardants (eBFRs) were evaluated in 41 kelp samples from the main kelp producing areas in China. The concentrations of total PCBs, PBDEs and eBFRs were in the range of 0.321-4.24 ng/g dry weight (dw), 0.255-25.5 ng/g dw and 3.00 × 10-3-47.2 ng/g dw in kelp, respectively. The pollutant pattern was dominated by decabromodiphenyl ethane (DBDPE, 13.0 ± 11.7 ng/g dw) followed in decreasing order by BDE-209 (2.74 ± 4.09 ng/g dw), CB-11 (1.32 ± 1.06 ng/g dw). The tested results showed that kelp could reflect the pollution status of PCBs, PBDEs and eBFRs, indicating the suitability of kelp as a biomonitor of these harmful substances. Finally, the data obtained was used to evaluate human non-cancer and cancer risks of PCBs and PBDEs via kelp consumption for Chinese. Though the calculated risk indices were considered acceptable according to the international standards even in the worst scenarios, the POPs levels in kelp should be monitored continuously as a good environmental indicator.
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Poluentes Ambientais , Retardadores de Chama , Bifenilos Policlorados , Poluentes Químicos da Água , Humanos , Bifenilos Policlorados/análise , Poluentes Orgânicos Persistentes , Éteres Difenil Halogenados/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Poluentes Ambientais/análise , China , Retardadores de Chama/análiseRESUMO
To assess the disruptions of brain white matter (WM) structural network in children with obstructive sleep apnea (OSA) using diffusion kurtosis imaging (DKI). We use DKI tractography to construct individual whole-brain, region-level WM networks in 40 OSA and 28 healthy children. Then, we apply graph theory approaches to analyze whether OSA children would show altered global and regional network topological properties and whether these alterations would significantly correlate with the clinical characteristics of OSA. We found that both OSA and healthy children showed an efficient small-world organization and highly similar hub distributions in WM networks. However, characterized by kurtosis fractional anisotropy (KFA) weighted networks, OSA children exhibited decreased global and local efficiency, increased shortest path length compared with healthy children. For regional topology, OSA children exhibited significant decreased nodal betweenness centrality (BC) in the bilateral medial orbital superior frontal gyrus (ORBsupmed), right orbital part superior frontal gyrus (ORBsup), insula, postcentral gyrus, left middle temporal gyrus (MTG), and increased nodal BC in the superior parietal gyrus, pallidum. Intriguingly, the altered nodal BC of multiple regions (right ORBsupmed, ORBsup and left MTG) within default mode network showed significant correlations with sleep parameters for OSA patients. Our results suggest that children with OSA showed decreased global integration and local specialization in WM networks, typically characterized by DKI tractography and KFA metric. This study may advance our current understanding of the pathophysiological mechanisms of impaired cognition underlying OSA.
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Apneia Obstrutiva do Sono , Substância Branca , Criança , Humanos , Substância Branca/diagnóstico por imagem , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Apneia Obstrutiva do Sono/diagnóstico por imagemRESUMO
The continuously increased production of various chemicals and their release into environments have raised potential negative effects on ecological health. However, traditional labor-intensive assessment methods cannot effectively and rapidly evaluate these hazards, especially for chronic risk. In this study, machine learning (ML) was employed to construct quantitative structure-activity relationship (QSAR) models, enabling the prediction of chronic toxicity to aquatic organisms by leveraging the molecular characteristics of pollutants, namely, the molecular descriptors, fingerprints, and graphs. The limited dataset size hindered the notable advantages of the graph attention network (GAT) model for the molecular graphs. Considering computational efficiency and performance (R2 = 0.78; RMSE = 0.77), XGBoost (XGB) was used for reliable QSAR-ML models predicting chronic toxicity using small- or medium-sized tabular data and the molecular descriptors. Further kernel density estimation analysis confirmed the high accuracy of the model for pollutant concentrations ranging from 10-3 to 102 mg/L, effectively aligning with most environmental scenarios. Model interpretation showed SlogP and exposure duration as the primary influential factors. SlogP, representing the distribution coefficient of a molecule between lipophilic and hydrophilic environments, had a negative effect on the toxicity outcomes. Additionally, the exposure duration played a crucial role in determining the chronic toxicity. Finally, the chronic toxicity data of bisphenol A validated the robustness and reliability of the model established in this research. Our study provided a robust and feasible methodology for chronic ecological risk evaluation of various types of pollutants and could facilitate and increase the use of ML applications in environmental fields.
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Poluentes Ambientais , Aprendizado de Máquina , Reprodutibilidade dos Testes , Medição de Risco , Relação Quantitativa Estrutura-AtividadeRESUMO
Microcephaly-capillary malformation syndrome (MIC-CAP) and Mowat-Wilson syndrome (MWS) are both rare hereditary diseases with several overlapping symptoms. We here report a Chinese patient simultaneously affected by MIC-CAP and MWS, presenting with moderate anaemia because of repeated, unilateral refractory epistaxis. The girl was initially diagnosed with MWS after discovery of a pathogenic nonsense mutation in ZEB2. Starting from the age of 3 years old, the child experienced repeated epistaxis on the right side without obvious incentive or trauma. The bleeding was quite difficult to stop and her hemoglobin dropped from 124 g/L to 64 g/L in three months. Both coagulation disorders and allergic rhinitis were excluded by extensive workup and experimental therapeutics. Retrospective genetic analysis revealed that she carried two novel compound heterozygous mutations in STAMBP (c.610T > C: p.Ser204Pro and c.945C > G: p.Asn315Lys). This case report demonstrates a rare presentation of MIC-CAP in the pediatric population and enriches the variant spectrum of STAMBP.
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Various studies have highlighted the important associations between obstructive sleep apnea (OSA) and gut microbiota and related metabolites. Nevertheless, the establishment of causal relationships between these associations remains to be determined. Multiple mendelian randomization (MR) analyses were performed to genetically predict the causative impact of 196 gut microbiota and 83 metabolites on OSA. Two-sample MR was used to assess the potential association, and causality was evaluated using inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods. Multivariable MR (MVMR) was employed to ascertain the causal independence between gut microbiota and the metabolites linked to OSA. Additionally, Cochran's Q test, the MR Egger intercept test and the MR Steiger test were used for the sensitivity analyses. The analysis of the 196 gut microbiota revealed that genus_Ruminococcaceae (UCG009) (PIVW = 0.010) and genus_Subdoligranulum (PIVW = 0.041) were associated with an increased risk of OSA onset. Conversely, Family_Ruminococcaceae (PIVW = 0.030), genus_Coprococcus2 (PWM = 0.025), genus_Eggerthella (PIVW = 0.011), and genus_Eubacterium (xylanophilum_group) (PIVW = 0.001) were negatively related to the risk of OSA. Among the 83 metabolites evaluated, 3-dehydrocarnitine, epiandrosterone sulfate, and leucine were determined to be potential independent risk factors associated with OSA. Moreover, the reverse MR analysis demonstrated a suggestive association between OSA exposure and six microbiota taxa. This study offers compelling evidence regarding the potential beneficial or detrimental causative impact of the gut microbiota and its associated metabolites on OSA risk, thereby providing new insights into the mechanisms of gut microbiome-mediated OSA development.
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Microbioma Gastrointestinal , Lactobacillales , Microbiota , Apneia Obstrutiva do Sono , Humanos , Microbioma Gastrointestinal/genética , Análise da Randomização Mendeliana , Causalidade , Clostridiales , Apneia Obstrutiva do Sono/genética , Estudo de Associação Genômica AmplaRESUMO
Unraveling the molecular mechanisms for COVID-19-associated encephalopathy and its immunopathology is crucial for developing effective treatments. Here, we utilized single-cell transcriptomic analysis and integrated clinical observations and laboratory examination to dissect the host immune responses and reveal pathological mechanisms in COVID-19-associated pediatric encephalopathy. We found that lymphopenia was a prominent characteristic of immune perturbation in COVID-19 patients with encephalopathy, especially those with acute necrotizing encephalopathy (AE). This was characterized a marked reduction of various lymphocytes (e.g., CD8+ T and CD4+ T cells) and significant increases in other inflammatory cells (e.g., monocytes). Further analysis revealed activation of multiple cell apoptosis pathways (e.g., granzyme/perforin-, FAS- and TNF-induced apoptosis) may be responsible for lymphopenia. A systemic S100A12 upregulation, primarily from classical monocytes, may have contributed to cytokine storms in patients with AE. A dysregulated type I interferon (IFN) response was observed which may have further exacerbated the S100A12-driven inflammation in patients with AE. In COVID-19 patients with AE, myeloid cells (e.g., monocytic myeloid-derived suppressor cells) were the likely contributors to immune paralysis. Finally, the immune landscape in COVID-19 patients with encephalopathy, especially for AE, were also characterized by NK and T cells with widespread exhaustion, higher cytotoxic scores and inflammatory response as well as a dysregulated B cell-mediated humoral immune response. Taken together, this comprehensive data provides a detailed resource for elucidating immunopathogenesis and will aid development of effective COVID-19-associated pediatric encephalopathy treatments, especially for those with AE.
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COVID-19 , Linfopenia , Humanos , Criança , Linfócitos T CD8-Positivos , COVID-19/genética , Proteína S100A12 , Transcriptoma/genética , Linfócitos T CD4-Positivos , Linfopenia/genéticaRESUMO
CONTEXT: Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine's active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD's major components remains unclear. OBJECTIVE: This study evaluates the herb-drug interaction between DBD's major components and gemcitabine and validates the underlying pharmacokinetic mechanism. MATERIALS AND METHODS: The pharmacokinetics of 3.6 g/kg DBD with and without a single-dose administration of 50 mg/kg gemcitabine was investigated in Sprague-Dawley rats. The effects of gemcitabine on intestinal permeability, hepatic microsomal enzymes in rat tissues, and CYP3A overexpressing HepG2 cells were determined using western blot analysis. RESULTS: The combination of gemcitabine significantly altered the pharmacokinetic profiles of DBD's major components in rats. The Cmax and AUC of calycosin-7-O-ß-d-glucoside notably increased through sodium-glucose transporter 1 (SGLT-1) expression promotion. The AUC of ligustilide and ferulic acid was also significantly elevated with the elimination half-life (t1/2) prolonged by 2.4-fold and 7.8-fold, respectively, by down-regulating hepatic CYP3A, tight junction proteins zonula occludens-1 (ZO-1) and occludin expression. DISCUSSION AND CONCLUSIONS: Gemcitabine could modulate the pharmacokinetics of DBD's major components by increasing intestinal permeability, enhancing transporter expression, and down-regulating CYP3A. These findings provide critical information for clinical research on DBD as an adjuvant for NSCLC with gemcitabine and help make potential dosage adjustments more scientifically and rationally.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Ratos , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gencitabina , Citocromo P-450 CYP3A , Regulação para Baixo , Ratos Sprague-Dawley , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Fe0-mediated autotrophic denitrification (ADN) can be suppressed by iron oxide coverage resulting from Fe0 corrosion. The mixotrophic denitrification (MDN) coupling Fe0-mediated ADN with heterotrophic denitrification (HDN) can circumvent the weakening of Fe0-mediated ADN over operation time. But the interaction between HDN and Fe0-mediated ADN for nitrogen removal of secondary effluent with deficient bioavailable organics remains unclear. When the influent COD/NO3--N ratio increased from 0.0 to 1.8-2.1, the TN removal efficiency was promoted significantly. The increased carbon source did not inhibit ADN, but promoted ADN and HDN synchronously. The formation of extracellular polymeric substances (EPS) was also facilitated concomitantly. Protein (PN) and humic acid (HA) in EPS increased significantly, which capable of accelerating electron transfer of denitrification. Due to that the electron transfer of HDN occurs intracellularly, the EPS with the capacity of accelerating electron transfer had a negligible influence on HDN. But for Fe0-mediated ADN, the increased EPS as well as corresponding PN and HA facilitated TN and NO3--N removal significantly, while accelerated the electron release originating from Fe0 corrosion. The bioorganic-Fe complexes were generated on Fe0 surface after used, meaning that the soluble EPS and soluble microbial products (SMP) participated in the electron transfer of Fe0-mediated ADN. The coexistence of HDN and ADN denitrifiers demonstrated the synchronous enhancement of HDN and ADN by the external carbon source. From the perspective of EPS and related SMP, the insight of enhancing Fe0-mediated ADN by external carbon source is beneficial to implement high-efficiency MDN for organics-deficient secondary wastewater.
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Desnitrificação , Matriz Extracelular de Substâncias Poliméricas , Carbono , Reatores Biológicos , Processos Autotróficos , Nitrogênio , NitratosRESUMO
Due to the far distance impact on resident, aquatic and soil ecosystem health, food waste disposal becomes the focus of municipal waste strategy in developing countries. Shanghai is a leading city in China, its evolution of food waste management can indicate the coming future of the nation. In this city, from 1986 to 2020, the open dumping, landfill and incineration of food waste had been gradually banned, replaced by centralized compost and anaerobic digestion and other recovery ways. This study selected ten scenarios, ever used for food/mixed waste disposal in Shanghai, and analyzed the environmental impact change during the period 1986-2020. Life cycle assessment showed that although the generation of food waste raised rapidly, the total environmental impact, which was dominated by Freshwater Aquatic Ecotoxicity Potential, displayed a sharp decrease as 96.09 %, and Global Warming Potential decreased by 28.14 %. Substantial efforts should be made to improve the collection rate of biogas and landfill gas to reduce environmental impact, and quality of residues from anaerobic digestion and compost plants should be improved and utilized in its legal ways. Driving forces for the goal of sustainable food waste management in Shanghai involved economic development, environmental regulations and the supporting national/local standards.
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Eliminação de Resíduos , Gerenciamento de Resíduos , Alimentos , Ecossistema , Resíduos Sólidos/análise , Países em Desenvolvimento , China , Instalações de Eliminação de Resíduos , IncineraçãoRESUMO
Municipal solid waste management and disposal in China have significantly evolved since 2000. Due to China's vast land area and significant socioeconomic and geographic disparities, nationwide waste management strategies need to be further evaluated. This study quantified the effect of social, economic, and geographic drivers on municipal waste disposal activities in 31 provincial-level administrative regions from 2003 to 2020, by establishing a methodology integrated by two-way fixed effects regression model, panel random forest, and spatial Durbin model. The results showed, in the past two decades, socio-economic-geo indicators significantly co-decided the landfill and incineration activities. In particular, the explanatory ability of GDP per capita was above 45%, while land resources and city size also showed great significance. Spatial autocorrelation analysis showed that the relationship between landfill/incineration rates and socio-economic-geo drivers changed notably from unobvious to significant with economic growth. Furthermore, the local economy and land resources displayed more impact than those of the neighboring regions, while sci-tech and education showed clear spatial spillover effects. Chinese government would carefully assess the full-scale promotion policy of incineration plants, landfill is still hold as a reasonable option for regions with specific socio-economic-geo conditions.
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Eliminação de Resíduos , China , Incineração , Eliminação de Resíduos/métodos , Fatores Socioeconômicos , Resíduos Sólidos/análise , Instalações de Eliminação de ResíduosRESUMO
Wastewater-based epidemiology (WBE) is an objective approach for the estimation of population-level exposure to a wide range of substances, in which the use of a population biomarker (PB) could significantly reduce back-calculation errors. Although some endogenous or exogenous compounds such as cotinine and other hormones have been developed as PBs, more PBs still need to be identified and evaluated. This study aimed to propose a novel method to estimate population parameters from the mass load of metal ion biomarkers in wastewater, and estimate the consumption of tobacco in 24 cities in Southern China using the developed method. Daily wastewater samples were collected from 234 wastewater treatment plants (WWTPs) in 24 cities in Southern China. Atomic absorption spectroscopy (AAS) was applied to determine the concentrations of common health-related metal ions in wastewater, including sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), iron (Fe), and zinc (Zn), and compared them with the daily mass load of cotinine corresponding to catchment populations. The concentrations of cotinine in wastewater samples were measured using liquid chromatography-tandem mass spectrometry. There were clear and strong correlations between the target metal ion equivalent population and census data. The correlation coefficients (R) were RK = 0.78, RNa = 0.66, RCa = 0.81, RMg = 0.77, and RFe = 0.69, at p < 0.01 and R2 > 0.6. Subsequently, the combination of WBE and metal ion PBs was used to estimate tobacco consumption. Daily consumption of nicotine was estimated to be approximately 1.76 ± 1.19 mg/d/capita, equivalent to an average of 13.0 ± 8.75 cigarettes/d being consumed by smokers. The data on tobacco consumption in this study were consistent with those in traditional surveys in Southern China. The metal ion potassium is an appropriate PB for reflecting the real-time population and could be used to evaluate the tobacco consumption in WBE study.
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Cotinina , Águas Residuárias , Cotinina/análise , Uso de Tabaco/epidemiologia , Cidades , China/epidemiologia , Potássio/análise , Biomarcadores , Cálcio/análiseRESUMO
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is currently the deadliest infectious disease in human that can evolve to severe forms. A comprehensive immune landscape for Mtb infection is critical for achieving TB cure, especially for severe TB patients. We performed single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing of 213,358 cells from 27 samples, including 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases). Two published profiles of latent TB infection were integrated for the analysis. We observed an obviously elevated proportion of inflammatory immune cells (e.g., monocytes), as well as a markedly decreased abundance of various lymphocytes (e.g., NK and γδT cells) in severe patients, revealing that lymphopenia might be a prominent feature of severe disease. Further analyses indicated that significant activation of cell apoptosis pathways, including perforin/granzyme-, TNF-, FAS- and XAF1-induced apoptosis, as well as cell migration pathways might confer this reduction. The immune landscape in severe patients was characterized by widespread immune exhaustion in Th1, CD8+T and NK cells as well as high cytotoxic state in CD8+T and NK cells. We also discovered that myeloid cells in severe TB patients may involve in the immune paralysis. Systemic upregulation of S100A12 and TNFSF13B, mainly by monocytes in the peripheral blood, may contribute to the inflammatory cytokine storms in severe patients. Our data offered a rich resource for understanding of TB immunopathogenesis and designing effective therapeutic strategies for TB, especially for severe patients.
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Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Humanos , Transcriptoma , Células Matadoras NaturaisRESUMO
OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. CONCLUSION: The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.
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Infecções Comunitárias Adquiridas , Pneumonia , Proteômica , Criança , Pré-Escolar , Humanos , Coagulação Sanguínea , Proteína C-Reativa , Morte Celular , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Metabolômica , Pneumonia/sangue , Pneumonia/diagnósticoRESUMO
Sustainable management of household solid waste (HSW) is an essential step in realizing the development of a circular economy (CE). However, for many developing countries, HSW sorting is evolving incrementally, and focusing on the intervention role of policy and the sorting behaviour of residents can help achieve sustainable waste management. This study aims to investigate the main determinants of residents' HSW sorting behaviour and how policy particularly contributes to it. Drawing upon the theory of planned behaviour (TPB) and incorporating experiences, a conceptual framework is tested on a sample of Chinese residents in Shanghai (n = 560, from November to December 2020) using structural equation modelling analysis. The empirical results show that experience and behavioural intention greatly influence HSW sorting behaviour. Moreover, the positive attitude of residents promotes the success of HSW sorting. Subjective norms and perceived behaviour control indirectly affect behavioural intention and behaviour via attitude. The findings of this study provide policymakers with critical factors for the successful implementation of HSW sorting. We also propose policy implications to maintain and improve sorting efficiency from the perspective of residents (education, communication and publicity), neighbourhood committees (degree and efficiency of supervision) and property management companies (good infrastructure, services and processes).
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Resíduos Sólidos , Gerenciamento de Resíduos , Opinião Pública , China , Intenção , Atitude , Inquéritos e Questionários , PolíticasRESUMO
Respiratory syncytial virus (RSV) is an important pathogen causing pneumonia in children. Few studies have used multi-omics data to investigate the pathogenies of RSV pneumonia. Here, metabolomics was first used to identify potential biomarkers for RSV diagnosis. In the training cohort, serum from 36 healthy controls (HCs), 45 RSV pneumonia children, and 32 infectious disease controls (IDCs) were recruited. After analyses, six metabolites had potential diagnostic value. Using an independent cohort of 49 subjects, two biomarkers (neuromedin N and histidyl-proline diketopiperazine) were validated. Next, multi-omics analysis were applied to analyze the pathogenies of RSV pneumonia. Accumulation of collagen in the serum of RSVs indicated that RSV infection could lead to increased levels of soluble collage. Activation of the complement system and imbalance in lipid metabolism were also observed in RSV patients. The multi-omics analysis presented here revealed the signature protein and metabolite changes in serum caused by RSV infection.