ABSTRACT
The tumor microenvironment (TME) has a significant impact on tumor growth and immunotherapy efficacies. However, the precise cellular interactions and spatial organizations within the TME that drive these effects remain elusive. Using advanced multiplex imaging techniques, we have discovered that regulatory T cells (Tregs) accumulate around lymphatic vessels in the peripheral tumor stroma. This localized accumulation is facilitated by mature dendritic cells enriched in immunoregulatory molecules (mregDCs), which promote chemotaxis of Tregs, establishing a peri-lymphatic Treg-mregDC niche. Within this niche, mregDCs facilitate Treg activation, which in turn restrains the trafficking of tumor antigens to the draining mesenteric lymph nodes, thereby impeding the initiation of anti-tumor adaptive immune responses. Disrupting Treg recruitment to mregDCs inhibits tumor progression. Our study provides valuable insights into the organization of TME and how local crosstalk between lymphoid and myeloid cells suppresses anti-tumor immune responses.
Subject(s)
Dendritic Cells , T-Lymphocytes, Regulatory , Tumor Microenvironment , T-Lymphocytes, Regulatory/immunology , Animals , Tumor Microenvironment/immunology , Mice , Dendritic Cells/immunology , Dendritic Cells/metabolism , Humans , Antigens, Neoplasm/immunology , Antigens, Neoplasm/metabolism , Lymphatic Vessels/immunology , Lymphatic Vessels/metabolism , Mice, Inbred C57BL , Lymph Nodes/immunology , Cell Line, Tumor , Neoplasms/immunology , Neoplasms/metabolismABSTRACT
BACKGROUND: Esophageal cancer (EC) is a highly lethal disease lacking early detection approaches. We previously identified that OTOP2 and KCNA3 were specifically hypermethylated in circulating cell-free DNA from patients with EC. We then developed a blood-based methylation assay targeting OTOP2 and KCNA3 (named "IEsohunter") for esophageal cancer noninvasive detection. This double-blinded, multicenter, prospective study aimed to comprehensively evaluate its clinical diagnostic performance. METHODS: Participants with EC, high-grade intraepithelial neoplasia (HGIN), other malignancies, benign gastrointestinal lesions, or no abnormalities were prospectively enrolled from 5 tertiary referral centers across China. Peripheral blood samples were collected, followed by plasma cell-free DNA methylation analysis using the IEsohunter test based on multiplex quantitative polymerase chain reaction adopting an algorithm-free interpretation strategy. The primary outcome was the diagnostic accuracy of IEsohunter test for EC. RESULTS: We prospectively enrolled 1116 participants, including 334 patients with EC, 71 with HGIN, and 711 controls. The areas under the receiver operating characteristic curves of the IEsohunter test for detecting EC and HGIN were 0.903 (95% CI 0.880-0.927) and 0.727 (95% CI 0.653-0.801), respectively. IEsohunter test showed sensitivities of 78.5% (95% CI 69.1-85.6), 87.3% (95% CI 79.4-92.4), 92.5% (95% CI 85.9-96.2), and 96.9% (95% CI 84.3-99.8) for stage I-IV EC, respectively, with an overall sensitivity of 87.4% (95% CI 83.4-90.6) and specificity of 93.3% (95% CI 91.2-94.9) for EC detection. The IEsohunter test status turned negative (100.0%, 47/47) after surgical resection of EC. CONCLUSIONS: The IEsohunter test showed high diagnostic accuracy for EC detection, indicating that it could potentially serve as a tool for noninvasive early detection and surveillance of EC.
Subject(s)
DNA Methylation , Esophageal Neoplasms , Humans , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/genetics , Esophageal Neoplasms/blood , Male , Female , Prospective Studies , Middle Aged , Double-Blind Method , Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Cell-Free Nucleic Acids/blood , AdultABSTRACT
Fecal microbiota transplantation (FMT) can induce clinical remission in ulcerative colitis (UC) patients. Enemas, nasoduodenal tubes, and colonoscopies are the most common routes for FMT administration. However, there is a lack of definitive evidence regarding the effectiveness of capsulized FMT treatment in UC patients. In this study, we administered capsulized FMT to 22 patients with active UC to assess the efficiency of capsulized FMT and determine the specific bacteria and metabolite factors associated with the response to clinical remission. Our results showed that the use of capsulized FMT was successful in the treatment of UC patients. Capsulized FMT induced clinical remission and clinical response in 57.1% (12 of 21) and 76.2% (16 of 21) of UC patients, respectively. Gut bacterial richness was increased after FMT in patients who achieved remission. Patients in remission after FMT exhibited enrichment of Alistipes sp. and Odoribacter splanchnicus, along with increased levels of indolelactic acid. Patients who did not achieve remission exhibited enrichment of Escherichia coli and Klebsiella and increased levels of biosynthesis of 12,13-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid) and lipopolysaccharides. Furthermore, we identified a relationship between specific bacteria and metabolites and the induction of remission in patients. These findings may provide new insights into FMT in UC treatment and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects. (This study has been registered at ClinicalTrails.gov under registration no. NCT03426683). IMPORTANCE Fecal microbiota transplantation has been successfully used in patients. Recently, capsulized FMT was reported to induce a response in patients with UC. However, limited patients were enrolled in such studies, and the functional factors of capsulized FMT have not been reported in the remission of patients with UC. In this study, we prospectively recruited patients with UC to receive capsulized FMT. First, we found that capsulized FMT could induce clinical remission in 57.1% of patients and clinical response in 76.2% after 12 weeks, which was more acceptable. Second, we found a relationship between the decrease of opportunistic pathogen and lipopolysaccharide synthesis in patients in remission after capsulized FMT. We also identified an association between specific bacteria and metabolites and remission induction in patients after capsulized FMT. These findings put forward a possibility for patients to receive FMT at home and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects.
Subject(s)
Colitis, Ulcerative , Communicable Diseases , Gastrointestinal Microbiome , Humans , Bacteria , Colitis, Ulcerative/therapy , Colitis, Ulcerative/microbiology , Fecal Microbiota Transplantation/methods , Feces/microbiology , Treatment OutcomeABSTRACT
To control the spread and transmission of airborne particles (especially SARS-CoV-2 coronavirus, recently) in the indoor environment, many control strategies have been employed. Comparisons of these strategies enable a reasonable choice for indoor environment control and cost-effectiveness. In this study, a series of experiments were conducted in a full-scale chamber to simulate a conference room. The control effects of four different strategies (a ventilation system (320 m3/h) with and without a baffle, a specific type of portable air cleaner (400 m3/h) and a specific type of desk air cleaner (DAC, 160 m3/h)) on the transportation of particles of different sizes were studied. In addition, the effects of coupling the ventilation strategies with five forms of indoor airflow organization (side supply and side or ceiling return, ceiling supply and ceiling or side return, floor supply and ceiling return) were evaluated. The cumulative exposure level (CEL) and infection probability were selected as evaluation indexes. The experimental results showed that among the four strategies, the best particle control effect was achieved by the PAC. The reduction in CEL for particles in the overall size range was 22.1% under the ventilation system without a baffle, 34.3% under the ventilation system with a baffle, 46.4% with the PAC, and 10.1% with the DAC. The average infection probabilities under the four control strategies were 11.3-11.8%, 11.1-11.8%, 9.1-9.5%, and 18.2-19.7%, respectively. Among the five different forms of airflow organization, the floor supply and ceiling return mode exhibited the best potential ability to remove particles.
ABSTRACT
Background: Colorectal cancer (CRC) is an insidious malignancy and the occurrence of chemotherapy resistance and toxicity seriously limits its clinical efficacy. Insect Compound Particle [Chong Yao Fu Fang (CYFF)] is a traditional Chinese medicine (TCM) compound based on the concepts of "invigorating spleen for strengthening vital qi" and "collateral disease theory". In long-term clinical application, it can reduce the toxicity of CRC chemotherapy and improve the anti-tumor effect. However, there is currently a lack of high-quality clinical evidence to prove the clinical efficacy and safety of CYFF in the treatment of CRC. Methods: We plan to include 262 patients with locally advanced stage III CRC who had undergone surgery and achieved R0 resection. These patients will be randomized into a CYFF group (treated with CYFF combined with chemotherapy) and a control group (treated with placebo plus chemotherapy) at a 1:1 ratio. The patients were routinely followed-up every 2 weeks within 2 months and every 4 weeks after 2 months after the treatment, every 3 months within 1 year, and every 6 months after 1 year. The primary endpoint is disease-free survival (DFS), defined as the time from random assignment to recurrence of primary CRC or death from any cause. The secondary endpoints include overall survival (OS) (defined as the time from randomization to death from any cause), safety [any adverse events (AEs)], and the Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ-CR38) score. Conclusions: Compared with previous studies, our current study applies CYFF plus basic adjuvant chemotherapy, which is expected to achieve better efficacy and longer survival than standard chemotherapy, and reduce the toxic and side effects of chemotherapy, improve the safety of clinical treatment. In addition, our present study is the first clinical study to evaluate the safety and efficacy of CYFF in combination with chemotherapy in the treatment of stage III CRC after R0 resection. Trial Registration: This clinical trial has been registered in the Chinese Clinical Trial Registry (ChiCTR) (registration No. ChiCTR2000037568; August 28, 2020).
ABSTRACT
OBJECTIVES: This study aims to develop and validate a radiomics nomogram based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to noninvasively predict axillary lymph node (ALN) metastasis in breast cancer. METHODS: This retrospective study included 263 patients with histologically proven invasive breast cancer and who underwent DCE-MRI examination before surgery in two hospitals. All patients had a defined ALN status based on pathological examination results. Regions of interest (ROIs) of the primary tumor and ipsilateral ALN were manually drawn. A total of 1,409 radiomics features were initially computed from each ROI. Next, the low variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) algorithms were used to extract the radiomics features. The selected radiomics features were used to establish the radiomics signature of the primary tumor and ALN. A radiomics nomogram model, including the radiomics signature and the independent clinical risk factors, was then constructed. The predictive performance was evaluated by the receiver operating characteristic (ROC) curves, calibration curve, and decision curve analysis (DCA) by using the training and testing sets. RESULTS: ALNM rates of the training, internal testing, and external testing sets were 43.6%, 44.3% and 32.3%, respectively. The nomogram, including clinical risk factors (tumor diameter) and radiomics signature of the primary tumor and ALN, showed good calibration and discrimination with areas under the ROC curves of 0.884, 0.822, and 0.813 in the training, internal and external testing sets, respectively. DCA also showed that radiomics nomogram displayed better clinical predictive usefulness than the clinical or radiomics signature alone. CONCLUSIONS: The radiomics nomogram combined with clinical risk factors and DCE-MRI-based radiomics signature may be used to predict ALN metastasis in a noninvasive manner.
Subject(s)
Breast Neoplasms , Nomograms , Humans , Female , Lymphatic Metastasis/diagnostic imaging , Retrospective Studies , Breast Neoplasms/pathology , Magnetic Resonance Imaging/methodsABSTRACT
Apolipoprotein H (APOH) is involved in lipid metabolism and functions as an acute-phase protein during hepatitis B virus (HBV) infection. Herein, we explored whether APOH acts on the development of fatty liver upon chronic HBV infection. Serum APOH level was significantly lower in cirrhosis patients than in healthy controls or patients with chronic infection. It showed sex bias, with elevated levels in female patients with chronic infection. Also, serum APOH levels were negatively correlated with HBV surface antigen (HBsAg) but positively correlated with albumin and triglyceride levels. In In vitro HBV infection model, HBV upregulated APOH expression in a non-temporal manner, and HBsAg levels were elevated by silencing APOH. RNA sequencing (RNA-seq) demonstrated bidirectional expression of APOH, which impacted the immunoregulation upon infection or the metabolic regulation in HepG2.2.15 cells. Then, ApoH -/- mice with persistent HBV replication displayed steatohepatitis and gut microbiota dysbiosis with synergistic sex differences. Our study deciphers the roles of APOH in chronic liver diseases.
ABSTRACT
In the production process of biomass energy with crop straw as the raw material, the indoor dust environment created by smashed plant fiber can affect the health of workers and lead to the risk of fire and explosions. The physical properties of biomass vary with the ambient air conditions, resulting in different deposition processes for airborne biomass particles. In this study, the deposition of biomass particles in different environments in an experimental chamber was examined by independently controlling the internal temperature and relative humidity. The results show that in the ambient temperature range of 20~40 °C and at a relative humidity of 25~65%, the water absorption rates of the biomass particles were 15.4~24.7%. The deposition rates of the airborne biomass particles with different sizes were 0.9~2.9 h-1, which positively correlated with the particle sizes in the same ambient conditions. The increase in ambient temperature and relative humidity promoted the deposition of biomass particles with diameters over 0.5 µm. For the particles with diameters below 0.5 µm, the deposition rates were nonlinearly related to the ambient temperature and relative humidity and were greater at lower temperatures. The significance levels of the factors influencing the particle deposition were particle size > ambient temperature > ambient relative humidity. For the biomass particles below 0.5 µm, the influence of the relative humidity on the deposition was much weaker than that of the temperature.
Subject(s)
Dust , Humans , Humidity , Temperature , Biomass , Particle Size , Dust/analysisABSTRACT
BACKGROUND AND AIMS: Endoscopy is increasingly performed for evaluating patients with ulcerative colitis (UC). However, its diagnostic accuracy is largely affected by the subjectivity of endoscopists' experience and scoring methods, and scoring of selected endoscopic images cannot reflect the inflammation of the entire intestine. We aimed to develop an automatic scoring system using deep-learning technology for consistent and objective scoring of endoscopic images and full-length endoscopic videos of patients with UC. METHODS: We collected 5875 endoscopic images and 20 full-length videos from 332 patients with UC who underwent colonoscopy between January 2017 and March 2021. We trained the artificial intelligence (AI) scoring system using these images, which was then used for full-length video scoring. To more accurately assess and visualize the full-length intestinal inflammation, we divided the large intestine into a fixed number of "areas" (cecum, 20; transverse colon, 20; descending colon, 20; sigmoid colon, 15; rectum, 10). The scoring system automatically scored inflammatory severity of 85 areas from every video and generated a visualized result of full-length intestinal inflammatory activity. RESULTS: Compared with endoscopist scoring, the trained convolutional neural network achieved 86.54% accuracy in the Mayo-scored task, whereas the kappa coefficient was .813 (95% confidence interval [CI], .782-.844). The metrics of the Ulcerative Colitis Endoscopic Index of Severity-scored task were encouraging, with accuracies of 90.7%, 84.6%, and 77.7% and kappa coefficients of .822 (95% CI, .788-.855), .784 (95% CI, .744-.823), and .702 (95% CI, .612-.793) for vascular pattern, erosions and ulcers, and bleeding, respectively. The AI scoring system predicted each bowel segment's score and displayed distribution of inflammatory activity in the entire large intestine using a 2-dimensional colorized image. CONCLUSIONS: We established a novel deep learning-based scoring system to evaluate endoscopic images from patients with UC, which can also accurately describe the severity and distribution of inflammatory activity through full-length intestinal endoscopic videos.
Subject(s)
Colitis, Ulcerative , Deep Learning , Humans , Colitis, Ulcerative/diagnostic imaging , Artificial Intelligence , Colonoscopy , Inflammation , Computers , Severity of Illness Index , Intestinal MucosaABSTRACT
To characterize the gut bacteriome, mycobiome and serum metabolome profiles in polycystic ovary syndrome (PCOS) patients with normal/overweight individuals and evaluate a potential microbiota-related diagnostic method development for PCOS, 16S rRNA and ITS2 gene sequencing using 88 fecal samples and 87 metabolome analysis from serum samples are conducted and PCOS classifiers based on multiomics markers are constructed. There are significant bacterial, fungal community and metabolite differences among PCOS patients and healthy volunteers with normal/overweight individuals. Healthy individuals with overweight/obesity display less abnormal metabolism than PCOS patients and uniquely higher abundance of the fungal genus Mortierella. Nine bacterial genera, 4 predicted pathways, 11 fungal genera and top 30 metabolites are screened out which distinguish PCOS from healthy controls, with AUCs of 0.84, 0.64, 0.85 and 1, respectively. The metabolite-derived model is more accurate than the microbe-based model in discriminating normal BMI PCOS (PCOS-LB) from normal BMI healthy (Healthy-LB), PCOS-HB from Healthy-HB. Featured bacteria, fungi, predicted pathways and serum metabolites display higher associations with free androgen index (FAI) in the cooccurrence network. In conclusion, our data reveal that hyperandrogenemia plays a central role in the dysbiosis of intestinal microecology and the change in metabolic status in patients with PCOS and that its effect exceeds the role of BMI. Healthy women with high BMI showed unique microbiota and metabolic features.The priority of predictive models in discriminating PCOS from healthy status in this study were serum metabolites, fungal taxa and bacterial taxa.
Subject(s)
Mycobiome , Polycystic Ovary Syndrome , Humans , Female , Overweight/complications , RNA, Ribosomal, 16S , Metabolome , Bacteria/geneticsABSTRACT
The COVID-19 pandemic has made significant impacts on public health, including human exposure to airborne pathogens. In healthcare facilities, the locations of return air vents in ventilation systems may have important effects on lowering airborne SARS-CoV-2 transmission. This study conducted experiments to examine the influence of different return air vents' heights (0.7 m, 1.2 m, and 1.6 m) on the particle removal effects in a simulated patient ward. Three different ventilation systems were examined: top celling air supply-side wall return (TAS), underfloor air supply-side wall return (UFAS) and side wall air supply-side wall return (SAS). CFD simulation was applied to further study the effects of return air inlets' heights (0.3 m, 0.7 m, 1.2 m, 1.6 m, and 2.0 m) and air exchange rates. The technique for order of preference by similarity to ideal solution (TOPSIS) analysis was used to calculate the comprehensive scores of 60 scenarios using a multi-criterion method to obtain the optimal return air inlets' heights. Results showed that for each additional 0.5 m distance in most working conditions, the inhalation fraction index of medical staff could be reduced by about 5-20%. However, under certain working conditions, even though the distances between the patients and medical personnel were different, the optimal heights of return air vents were constant. For TAS and UFAS, the optimal return air inlets' height was 1.2 m, while for SAS, the best working condition was 1.6 m air supply and 0.7 m air return. At the optimum return air heights, the particle decay rate per hour of SAS was 75% higher than that of TAS, and the rate of particle decay per hour of SAS was 21% higher than that of UFAS. The location of return air inlets could further affect the operating cost-effectiveness of ventilation systems: the highest operating cost-effectiveness was 8 times higher than the lowest one.
Subject(s)
Air Pollution, Indoor , COVID-19 , Air Pollution, Indoor/analysis , Air Pollution, Indoor/prevention & control , Bays , COVID-19/epidemiology , Hospitals , Humans , Pandemics , SARS-CoV-2 , Ventilation/methodsABSTRACT
BACKGROUND: Alcohol-related liver disease (ALD) is a major chronic liver ailment caused by alcohol overconsumption and abuse. Apolipoprotein H (APOH) participates in lipid metabolism and might have a potential regulatory role in ALD. Therefore, this study aimed to explore the effects of ApoH on alcohol-induced liver injury and gut microbiota dysbiosis. METHODS: ApoH-/- mice were generated and the synergic alcoholic steatohepatitis mouse model was constructed, which were used to assess liver function and pathological changes. RESULTS: ApoH-/- mice clearly exhibited spontaneous steatohepatitis. Severe hepatic steatosis was observed in alcohol-fed WT and ApoH-/- mice, in which ApoH expression was reduced post alcohol consumption. Moreover, RNA-seq and KEGG pathway analyses indicated that differential expression genes enriched in lipid metabolism and oxidation-reduction process between in alcohol-fed ApoH-/- mice and pair-fed control mice. Finally, gut microbiota diversity and composition were assessed by 16S rRNA Illumina next-generation sequencing. Alpha diversity of enterobacteria was lower in ApoH-/- mice with ethanol feeding than in ethanol-fed WT mice and all control-fed mice (P < 0.05). Moreover, KEGG enrichment analysis, using PICRUSt software, revealed that metabolic functions were activated in the gut microorganisms of ApoH-/- mice with ethanol feeding (P < 0.05). CONCLUSIONS: Alcohol-downregulated ApoH expression, leading to the progress of fatty liver disease and gut microbiota dysbiosis.
Subject(s)
Alcoholism , Fatty Liver , Gastrointestinal Microbiome , Liver Diseases , Animals , Down-Regulation , Dysbiosis/genetics , Dysbiosis/microbiology , Ethanol/toxicity , Fatty Liver/genetics , Mice , RNA, Ribosomal, 16S/genetics , beta 2-Glycoprotein I/pharmacologyABSTRACT
Background and aims: Inflammatory bowel disease (IBD) places a heavy medical burden on countries and families due to repeated and prolonged attacks, and the incidence and prevalence of IBD are increasing worldwide. Therefore, finding an effective treatment is a matter of great urgency. Glycerol monolaurate (GML), which has a twelve-carbon chain, is a compound naturally found in human breast milk. Some studies have shown that GML has antibacterial and anti-inflammatory effects. However, the specific mechanism of action remains unclear. Methods: Acute colitis was established in mice using 3% DSS, and glycerol monolaurate (500 mg·kg-1) was administered for two weeks. QPCR and western blotting were performed to examine the inflammatory status. Mice described were subjected to flow cytometry analysis for immune cell activation. Results: GML treated alleviated macroscopic symptoms such as shortened colons, increased spleen weight, and caused weight loss in mice with DSS-induced colitis. In addition, GML decreased the expression of pro-inflammatory factors (NF-α, IL-1ß and IL-1α) and increased the expression of anti-inflammatory factors (IL-10 and TGF-ß). GML inhibited the activation of the MAPK and NF-κB signalling pathways, improved tissue damage, and increased the expression of intestinal tight junction proteins. In addition, LPMCs extracted from intestinal tissue via flow cytometry showed that GML treatment led to a decrease of Th17 cells, Neutrophils and Macrophages. 16S rDNA sequencing showed that GML increased the abundance of commensal bacterium such as Akkermansia and Lactobacillus murinus. Conclusions: We showed that oral administration of GML ameliorated DSS-induced colitis by inhibiting infiltration of Th17 cells, Neutrophils, and Macrophages, protecting the intestinal mucosal barrier and altered the abundance of commensal bacterium. This study provides new insights into the biological function and therapeutic potential of GML in the treatment of IBD.
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is one of the primary causes of cirrhosis and a major risk factor for hepatocellular carcinoma and liver-related death. It has been correlated with changes in the gut microbiota, which promote its development by regulating insulin resistance, bile acid and choline metabolism, and inflammation. Recent studies suggested a controversial role of the stimulator of interferon genes (STING) in the development of NAFLD. Here, we showed that as an immune regulator, STING aggravates the progression of NAFLD in diet-induced mice and correlated it with the changes in hepatic lipid metabolism and gut microbiota diversity. After feeding wild-type (WT) and STING deletion mice with a normal control diet (NCD) or a high-fat diet (HFD), the STING deletion mice showed decreased lipid accumulation and liver inflammation compared with WT mice fed the same diet. In addition, STING specifically produced this hepatoprotective effect by inhibiting the activation of CD8+ T cells. The gut microbiota analysis revealed significant differences in intestinal bacteria between STING deletion mice and WT mice under the same diet and environmental conditions; moreover, differential bacterial genera were associated with altered metabolic phenotypes and involved in related metabolic pathways. Overall, our findings reveal the important regulatory role that STING plays in the progression of NAFLD. In addition, the change in intestinal microbiota diversity may be the contributing factor.
Subject(s)
Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Animals , Bacteria , CD8-Positive T-Lymphocytes/metabolism , Diet, High-Fat/adverse effects , Inflammation , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolismABSTRACT
The intestine is a potential location for berberine (BBR) to exert its therapeutic effects, but the understanding of the influences of BBR on the gut microbiota is limited. Through in vitro fermentation of human intestinal microbiota, we investigated the effects of BBR on microbiota composition and metabolism. The result indicated that BBR reduced the production of acetic acid and propionic acid and had no effect on the content of butyric acid. Analysis of the 16S rRNA gene-based community revealed that BBR increased the abundance of Faecalibacterium and decreased the abundance of Bifidobacterium, Streptococcus and Enterococcus. Through metabolomics analysis, BBR treatment regulated various amino acid metabolism pathways of intestinal microbiota, especially tyrosine, serine and L-glutamate. Our study presented direct impacts of BBR on the intestinal microbiota, which provided the probable targets of the therapies by BBR and supported further exploration of the underlying mechanisms.
Subject(s)
Berberine , Gastrointestinal Microbiome , Amino Acids/pharmacology , Berberine/pharmacology , Humans , Intestines , RNA, Ribosomal, 16S/geneticsABSTRACT
This study aimed to investigate whether serum indicators related to iron stores in the body are associated with clinical and endoscopic disease severity. Eighty-four patients with Crohn's disease (CD) and twenty-four healthy volunteers were included. The indicators related to iron stores were detected within one week after endoscopic and CT enterography examinations. Patients were divided into three groups according to the CDAI(Crohn's disease activity index)scores. Serum iron levels were decreased in all groups (p < 0.05), and the values of remission group were higher than those of moderate group (p < 0.001). The total iron binding capacity(TIBC)values of the moderate group were lower than those of the controls and the other groups (p < 0.05). None of the indicators differed significantly among the patients classified by SES-CD (p > 0.05). Underweight, decreased serum iron and TIBC were independent risk factors for moderate clinical disease. Combined detection of decreased serum iron and TIBC was helpful in differentiating severe patients. The sensitivity and specificity were 32.7% and 100%, respectively (AUC = 0.812, p < 0.01). Decreases in serum iron and TIBC were associated with the clinical activity of CD. Combined detection of the two indicators was conducive to screening serious disease.
Subject(s)
Crohn Disease , Crohn Disease/diagnosis , Endoscopy , Humans , Iron , Sensitivity and Specificity , Severity of Illness IndexABSTRACT
Walking-induced fluctuations have a significant influence on indoor airflow and pollutant dispersion. This study developed a method to quantify the robustness of ventilation systems in the control of walking-induced fluctuation control. Experiments were conducted in a full-scale chamber with four different kinds of ventilation systems: ceiling supply and side return (CS), ceiling supply and ceiling return (CC), side supply and ceiling return (SC), and side supply and side return (SS). The measured temperature, flow and pollutant field data was (1) denoised by FFT filtering or wavelet transform; (2) fitted by a Gaussian function; (3) feature-extracted for the range and time scale disturbance; and then (4) used to calculate the range scale and time scale robustness for different ventilation systems with dimensionless equations developed in this study. The selection processes for FFT filtering and wavelet transform, FFT filter cut-off frequency, wavelet function, and decomposition layers are also discussed, as well as the threshold for wavelet denoising, which can be adjusted accordingly if the walking frequency or sampling frequency differs from that in other studies. The results show that for the flow and pollutant fields, the use of a ventilation system can increase the range scale robustness by 19.7%-39.4% and 10.0%-38.8%, respectively; and the SS system was 7.0%-25.7% more robust than the other three ventilation systems. However, all four kinds of ventilation systems had a very limited effect in controlling the time scale disturbance.
ABSTRACT
BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test SaâªSc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and SaâªSc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and SaâªSc: 64.0% vs 73.4%). Fecal signature SaâªSc outperformed SaâªCEA/ScâªCEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of SaâªSc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).
Subject(s)
Stomach Neoplasms , Streptococcus constellatus , Early Detection of Cancer , Feces , Humans , Stomach Neoplasms/diagnosis , Streptococcus anginosus/genetics , Streptococcus constellatus/geneticsABSTRACT
The rapid spread and high level of morbidity of the SARS-CoV-2 virus during the COVID-19 pandemic has attracted considerable attention worldwide. Recent studies have shown that clothing is one of the vectors for the transport of airborne particles, including bioaerosols. This study developed a method that can both quantify the deposition of particles onto clothing and the resuspension of particles from clothing using a fluorescent-tracking technology and found that electrical tape can be used as a fluorescent particle collector on irregular clothing surfaces. Results show that 0.07%-6.61% of the fluorescent particles (FPs) previously loaded on the room flooring surfaces moved to the occupant's clothing during the 20-min sampling periods; the percentage depended on the type of activity and the range is for: office work, walking, and vacuuming. Furthermore, both the flooring type (carpet or vinyl composition tile) and flooring condition (clean or dirty) had significant effects on particle resuspension and transport to the occupant's clothing. The average particle deposition factor for carpet flooring was 2.7 (±1.4) times that for vinyl composition tile flooring, while the average particle deposition factor for dirty flooring was 2.4 (±1.6) times that for clean flooring. A multiple regression analysis shows that the activity type had the largest effect on the particle transport among all experimental variables. An additional experiment performed in a full-scale house shows that 46.8% of FPs formerly seeded on clothing resuspended from clothing and dispersed around the house during the 1-h period of light walking at a speed of 60 steps/min.