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BACKGROUND: Obesity is known as a risk factor for cardiovascular disease (CVD). However, there is an absence of preoperative cardiac risk assessment in bariatric surgery candidates and the incidence of CVD among these high-risk patients is still unknown. METHODS: A consecutive series of bariatric surgery candidates at two Chinese tertiary hospitals received coronary CT angiography or coronary angiography from 2017 to 2023. Patients were categorized as metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO) based on the presence or absence of MetS. CVD was diagnosed based on the maximum intraluminal stenosis > 1% in any of the segments of the major epicardial coronary arteries. Obstructive CVD was defined as coronary stenosis ≥ 50%. Binary multivariable logistic regression was performed to analyze the association between CVD and metabolic status. The number of principal MetS components was categorized into zero (without glycemic, lipid, and BP components), one (with one of the components), two (with any two components), and three (with all components) to explore their association with CVD. RESULTS: A total of 1446 patients were included in the study. The incidence of CVD and obstructive CVD were 31.7% and 9.6%. Compared with MHO patients, MUO patients had a significantly higher incidence of mild (13.7% vs. 6.1%, P < 0.05), moderate (7.4% vs. 0.8%, P < 0.05), and severe CVD (3.1% vs. 0%, P < 0.05). Following complete adjustment, compared with zero or one component, two principal MetS components was found to be associated with a notable increase in the risk of CVD (OR 2.05, 95% CI 1.18-3.58, P < 0.05); three principal MetS components were observed to have a higher risk of CVD and obstructive CVD (OR 2.68, 95% CI 1.56-4.62, P < 0.001; OR 3.93, 95% CI 1.19-12.93, P < 0.05). Each increase in the number of principal MetS components correlated with a 1.47-fold (95% CI 1.20-1.81, P < 0.001) and 1.78-fold (95% CI 1.24-2.55, P < 0.05) higher risk of CVD and obstructive CVD, respectively. CONCLUSION: This study reported the incidence of CVD based on multicenter bariatric surgery cohorts. CVD is highly prevalent in patients with obesity, especially in MUO patients. Increased number of principal MetS components will significantly elevate the risk of CVD.
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BACKGROUND: The Spike protein mutation severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to decreased protective effect of various vaccines and mAbs, suggesting that blocking SARS-CoV-2 infection by targeting host factors would make the therapy more resilient against virus mutations. Angiotensin-converting enzyme 2 (ACE2) is the host receptor of SARS-CoV-2 and its variants, as well as many other coronaviruses. Downregulation of ACE2 expression in the respiratory tract may prevent viral infection. Antisense oligonucleotides (ASOs) can be rationally designed on the basis of sequence data, require no delivery system, and can be administered locally. OBJECTIVE: We sought to design ASOs that can block SARS-CoV-2 by downregulating ACE2 in human airway. METHODS: ACE2-targeting ASOs were designed using a bioinformatic method and screened in cell lines. Human primary nasal epithelial cells cultured at the air-liquid interface and humanized ACE2 mice were used to detect the ACE2 reduction levels and the safety of ASOs. ASO-pretreated nasal epithelial cells and mice were infected and then used to detect the viral infection levels. RESULTS: ASOs reduced ACE2 expression on mRNA and protein level in cell lines and in human nasal epithelial cells. Furthermore, they efficiently suppressed virus replication of 3 different SARS-CoV-2 variants in human nasal epithelial cells. In vivo, ASOs also downregulated human ACE2 in humanized ACE2 mice and thereby reduced viral load, histopathologic changes in lungs, and increased survival of mice. CONCLUSIONS: ACE2-targeting ASOs can effectively block SARS-CoV-2 infection. Our study provides a new approach for blocking SARS-CoV-2 and other ACE2-targeting virus in high-risk populations.
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BACKGROUND: Despite the large patient base in Asia, the prognostic factors of patients with non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely undetermined. OBJECTIVE: We aimed to systematically investigate the predictive value of clinical and biological variables for non-eosinophilic CRSwNP. METHODS: Fifty-one patients with non-eosinophilic CRSwNP who underwent functional endoscopic surgery were recruited. Clinical information and assessment were comprehensively collected before and after surgery. A broad spectrum of biomarkers was measured in tissue homogenates using multiple assays. A random forest algorithm and stepwise logistic regression were used to construct clinical, biological, and combined models. RESULTS: A total of 41.2% of non-eosinophilic CRSwNP patients were uncontrolled more than 6 months after surgery. We identified one clinical variable (22-item Sino-Nasal Outcome Test score) and four biomarkers (programmed cell death ligand 1, platelet-derived growth factor subunit B [PDGF-ß], macrophage inflammatory protein-3b, and PDGF-α) that were significantly predictive of the surgical outcome. The clinical, biological, and combined models showed predictive ability with areas under the curve of 0.78, 0.83, and 0.89, respectively. PDGF-ß and programmed cell death ligand 1 were identified as independent biomarkers for the prognosis of patients with CRSwNP without considerable eosinophilic infiltration. CONCLUSION: This study shows that clinical and biological factors, such as the 22-item Sino-Nasal Outcome Test score and PDGF-ß, are predictive of the post-functional endoscopic surgical prognosis of non-eosinophilic CRSwNP patients.
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OBJECTIVE: The objective of this meta-analysis was to quantify the overall effects of gene mutations in the leptin-melanocortin pathway on short- and long-term weight loss after bariatric surgery. METHODS: MEDLINE, PubMed, and Embase were searched, and data were analyzed using ReviewManager (RevMan) version 5.4. The datasets were divided into two subgroups based on postoperative time, and the outcome measure was the percentage of total weight loss. Meta-regression analysis was performed, and the outcome was presented as the weighed mean difference of percentage of total weight loss. RESULTS: The results showed that patients with mutations in the leptin-melanocortin pathway experienced 3.03% lower total weight loss after bariatric surgery (mean difference, -3.03; 95% CI: -3.63 to -2.44), mainly reflected in lower long-term postoperative weight loss (mean difference, -3.43; 95% CI: -4.09 to -2.77), whereas mutation carriers exhibited a magnitude of short-term postoperative weight loss that was similar to patients without such mutations (total difference value, -1.13; 95% CI: -2.57 to 0.31). CONCLUSIONS: Mutations in leptin-melanocortin pathway genes reduce long-term weight loss after bariatric surgery, whereas this effect may not be reflected during the period of rapid weight loss within 12 months. These genetic variants increase the difficulties in maintaining patients' long-term weight loss.
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Cirugía Bariátrica , Leptina , Mutación , Pérdida de Peso , Humanos , Leptina/genética , Leptina/sangre , Pérdida de Peso/genética , Melanocortinas/genética , Obesidad Mórbida/cirugía , Obesidad Mórbida/genética , Transducción de Señal , Obesidad/cirugía , Obesidad/genéticaRESUMEN
Background: Bariatric surgery is an effective approach to weight loss, which may also affect thyroid function. However, alteration in thyroid-stimulating hormone (ΔTSH) and thyroid hormones after bariatric surgery and the relationship between thyroid function and postoperative weight loss still remains controversial. Methods: Data were collected from euthyroid patients with obesity who underwent sleeve gastrectomy and Roux-en-Y gastric bypass from 2017 to 2022. The alterations of free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), total triiodothyronine (TT3), and TSH were calculated 1 year after surgery. Pearson correlation analysis was used to assess the correlation between the percentage of total weight loss (%TWL) and ΔTSH. Multivariable linear regression was utilized to determine the association between %TWL and ΔTSH. Results: A total of 256 patients were included in our study. The mean %TWL was 28.29% after 1 year. TSH decreased from 2.33 (1.67, 3.04) uIU/mL to 1.82 (1.21, 2.50) uIU/mL (P < 0.001), FT3 decreased from 3.23 ± 0.42 pg/mL to 2.89 ± 0.41 pg/mL (P < 0.001), FT4 decreased from 1.11 ± 0.25 ng/dL to 1.02 ± 0.25 ng/dL (P < 0.001), TT3 decreased from 1.13 (1.00, 1.25) ng/mL to 0.89 (0.78, 1.00) ng/mL (P < 0.001), and TT4 decreased from 8.28 ± 1.69 ug/mL to 7.82 ± 1.68 ug/mL 1 year postoperatively (P < 0.001). %TWL was found to be significantly correlated to ΔTSH by Pearson correlation analysis (Pearson correlation coefficient = 0.184, P = 0.003), indicating that the more weight loss, the more TSH declined. After adjusting for covariates in multivariable linear regression, %TWL was found to be independently associated with ΔTSH (ß = 0.180 [95% confidence interval (CI), 0.048 - 0.312], P = 0.008). Moreover, %TWL was divided into 3 categorical groups (%TWL ≤ 25%, 25% < %TWL ≤ 35%, and %TWL > 35%) for further exploration, and was also found to be an independent predictor for ΔTSH after adjusting for covariates in multivariable linear regression (ß = 0.153 [95% CI, 0.019 - 0.287], P = 0.025). Conclusion: TSH, FT4, FT3, TT4, and TT3 decrease significantly 1 year after bariatric surgery. The decline in TSH is independently mediated by postoperative weight loss; the more the weight loss, the more the TSH decrease.
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Cirugía Bariátrica , Obesidad Mórbida , Glándula Tiroides , Hormonas Tiroideas , Humanos , Cirugía Bariátrica/efectos adversos , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Glándula Tiroides/fisiología , Tirotropina , Tiroxina , Triyodotironina , Pérdida de PesoAsunto(s)
Neoplasias de la Mama , Gastroscopios , Humanos , Femenino , Neoplasias de la Mama/cirugía , Mastectomía , ElectrónicaRESUMEN
To address the solid waste challenges associated with coal gasification fine ash, this study conducted a low-temperature alkali fusion de-ashing treatment to transform coal gasification fine ash into mineral-carbon adsorbent. The preparation process was simplified without grinding, carbonization and high-temperature (500-800 °C) activation treatment. The results demonstrate a positive linear correlation between the ash removal rate of the samples (measured during the preparation process, i.e., low-temperature alkaline fusion treatment of coal gasification fine ash) and their maximum equilibrium adsorption capacity for methylene blue. For the samples with an ash removal rate of 95.71 %, which exhibit a maximum adsorption capacity of 161.36 mg/g for methylene blue. The adsorption behavior of methylene blue on mineral-carbon adsorbent was a monolayer adsorption on the surface of homogeneous medium, involving both physical and chemical adsorption. The main adsorb rate-controlling steps for the samples with ash removal rates of 27.91-59.33 % and 95.71 % were the intra particle diffusion process and the liquid film diffusion process, respectively. The adsorption mechanism of methylene blue on the surface of mineral-carbon adsorbent involved electrostatic attraction and hydrogen bonding. The aforementioned results demonstrated the potential of coal gasification fine ash as an adsorbent material, providing new options for promoting the resource utilization and high-value applications of coal gasification fine ash.
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Ceniza del Carbón , Contaminantes Químicos del Agua , Temperatura , Adsorción , Carbono , Azul de Metileno , Carbón Mineral , Minerales , CinéticaRESUMEN
INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a serious inflammatory condition. Nasal fluids (NFs) present a noninvasive alternative to nasal biopsy for studying CRSwNP pathogenesis. We aimed to compare the protein and mRNA inflammation signature between nasal polyps (NPs) and NFs. METHOD: The performance of polyvinyl alcohol (PVA) sponges and NFs absorbable device (NFAD) for collecting NFs from 20 patients with CRSwNP was compared using the Luminex assay. The other group consisted of four healthy controls and an additional 21 CRSwNP patients (including eosinophilic CRSwNP [ECRSwNP] and non-eosinophilic CRSwNP [NECRSwNP]) for protein quantification by Olink platform and gene expression evaluation by RNA-sequencing. Spearman's analysis was performed to detect correlations between protein expression levels in NFs and clinical assessment variables. RESULTS: NFAD-collected NFs contained at least a 2-fold higher concentration of cytokines than that obtained using PVA sponge, and these cytokines levels are significantly associated with NPs (ρ > 0.45, p < 0.05). Differentially expressed proteins between NFs and NPs were significantly correlated in the ECRSwNP subgroup compared with controls (ρ = 0.41, p < 0.01). Levels of Th2/IL-13, MCP4, and CCL4, characteristic of eosinophilic infiltration, were increased in ECRSwNP patients. A significant correlation between gene and protein expression was observed (ρ = 0.34, p < 0.01). PDL2 levels in NFs were positively correlated with ECRSwNP postoperative recurrence, the nasal VAS, and SNOT-22 scores (ρ > 0.68, p < 0.05 for all). CONCLUSION: Our study revealed similarities and discrepancies in inflammatory signatures between NPs and NFs in the same CRSwNP patient.
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Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Humanos , Pólipos Nasales/genética , Pólipos Nasales/metabolismo , Rinitis/diagnóstico , Transcriptoma , Sinusitis/genética , Sinusitis/diagnóstico , Citocinas/metabolismo , Enfermedad CrónicaRESUMEN
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous and common upper airway disease divided into various inflammatory endotypes. Recent epidemiological findings showed a T helper 2 (Th2)-skewed dominance in CRSwNP patients. Histone modification alterations can regulate transcriptional and translational expression, resulting in abnormal pathogenic changes and the occurrence of diseases. Trimethylation of histone H3 lysine 4 (H3K4me3) is considered an activator of gene expression through modulation of accessibility for transcription, which is closely related to CRSwNP. H3K4me3 levels in the human nasal epithelium may change under Th2-biased inflammatory conditions, resulting in exaggerated local nasal Th2 responses via the regulation of naïve CD4+ T-cell differentiation. Here, we revealed that the level of SET and MYND domain-containing protein 3 (SMYD3)-mediated H3K4me3 was increased in NPs from Th2 CRSwNP patients compared with those from healthy controls. We demonstrated that SMYD3-mediated H3K4me3 is increased in human nasal epithelial cells under Th2-biased inflammatory conditions via S-adenosyl-L-methionine (SAM) production and further found that the H3K4me3high status of insulin-like growth factor 2 (IGF2) produced in primary human nasal epithelial cells could promote naïve CD4+ T-cell differentiation into Th2 cells. Moreover, we found that SAM production was dependent on the c-Myc/methionine adenosyltransferase 2A (MAT2A) axis in the nasal epithelium. Understanding histone modifications in the nasal epithelium has immense potential utility in the development of novel classes of therapeutics targeting Th2 polarization in Th2 CRSwNP. Video Abstract.
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Pólipos Nasales , Rinitis , Sinusitis , Humanos , Histonas , Rinitis/metabolismo , Rinitis/patología , Pólipos Nasales/metabolismo , Retroalimentación , Sinusitis/complicaciones , Sinusitis/metabolismo , Diferenciación Celular , N-Metiltransferasa de Histona-Lisina/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Metionina Adenosiltransferasa/metabolismoRESUMEN
Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with elevated levels of type 2 inflammatory cytokines and raised immunoglobulin concentrations in nasal polyp tissue. By using single-cell RNA sequencing, transcriptomics, surface proteomics, and T cell and B cell receptor sequencing, we found the predominant cell types in nasal polyps were shifted from epithelial and mesenchymal cells to inflammatory cells compared to nasal mucosa from healthy controls. Broad expansions of CD4 T effector memory cells, CD4 tissue-resident memory T cells, CD8 T effector memory cells and all subtypes of B cells in nasal polyp tissues. The T and B cell receptor repertoires were skewed in NP. This study highlights the deviated immune response and remodeling mechanisms that contribute to the pathogenesis of uncontrolled severe CRSwNP. CLINICAL IMPLICATIONS: We identified differences in the cellular compositions, transcriptomes, proteomes, and deviations in the immune profiles of T cell and B cell receptors as well as alterations in the intercellular communications in uncontrolled severe CRSwNP patients versus healthy controls, which might help to define potential therapeutic targets in the future.
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Pólipos Nasales , Rinitis , Sinusitis , Humanos , Rinitis/metabolismo , Pólipos Nasales/patología , Multiómica , Mucosa Nasal/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Enfermedad CrónicaAsunto(s)
Duodeno , Mucosa Intestinal , Ablación por Radiofrecuencia , Humanos , Duodeno/cirugía , Mucosa Intestinal/cirugíaRESUMEN
Coal gasification fine ash (CGFA) is characterized by high yield, high carbon content, and difficult recovery. This results in waste of coal resources and serious environmental pollution. To address this issue, a novel green deashing process is proposed in this study to modify CGFA into deashed carbon (DAC) with a high calorific value and an ash content of less than 5% through a low-temperature alkaline fusion process. Compared with traditional alkaline fusion (which is carried out at 600-1000 °C), low-temperature alkaline fusion treatment can efficiently remove ash minerals in the temperature range of 300-450 °C, which is beneficial to the efficient recovery of residual carbon in DA, while simultaneously improving the physicochemical properties and energy characteristics of DAC, thereby improving its combustion performance. At an alkali fusion temperature of 350 °C, a NaOH:DA ratio of 4.5:1, and a reaction time of 40 min, the resulting DAC product had ash content of 2.28%, combustible material recovery (CMR) of 82.03%, higher heating value (HHV) of 31.07 MJ kg-1, and SBET of 445.43 m2 g-1. In comparison, it was found that low-temperature alkali fusion significantly improved the deashing of CGFA when compared to existing deashing technologies. These results strongly suggest that this innovative deashing method can modify CGFA into a high-calorific value and low-N and S fuel, thereby providing a cost-effective and sustainable utilization method for CGFA.
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Background: Type 2 CRSwNP is characterized by severe symptoms, multiple comorbidities, longer recovery course and high recurrence rate. A simple and cost-effective diagnostic model for CRSwNP endotype integrating clinical characteristics and histopathological features is urgently needed. Objective: To establish a clinical diagnostic model of inflammatory endotype in CRSwNP based on the clinical characteristics, pathological characteristics, and cytokines profile in the polyp tissue of patients. Methods: A total of 244 participants with CRSwNP were enrolled at 2 different centers in China and Belgium from 2018 to 2020. IL-5 level of nasal polyp tissue was used as gold standard. Clinical characteristics were used to establish diagnostic models. The area under the receiver operating curve (AUC) was used to evaluate the diagnostic performance. The study was approved by the ethics board of the First Affiliated Hospital of Sun Yat-sen University ([2020] 302), and written informed consent was obtained from all subjects before inclusion. Results: In total, 134 patients from China (training set) and 110 patients from Belgium (validation set) were included. The logistic regression (LR) model in predicting inflammatory endotype of CRSwNP showed the AUC of 83%, which was better than the diagnostic performance of machine learning models (AUC of 61.14%-82.42%), and single clinical variables. We developed a simplified scoring system based on LR model which shows similar diagnostic performance to the LR model (P = 0.6633). Conclusion: The LR model in this diagnostic study provided greater accuracy in prediction of inflammatory endotype of CRSwNP than those obtained from the machine learning model and single clinical variable. This indicates great potential for the use of diagnostic model to facilitate inflammatory endotype evaluation when tissue cytokines are unable to be measured.
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Fallo Renal Crónico , Laparoscopía , Diálisis Peritoneal , Humanos , Cateterismo , Endoscopía , CatéteresAsunto(s)
Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Mastectomía , Neoplasias de la Mama/cirugía , EndoscopíaRESUMEN
OBJECTIVE: Polymer micelles were prepared (L-RSPMs) with luteolin and synthetic RA-SS-mPEG polymeric material before evaluation of their anti-inflammatory effect on 2, 4, 6-trinitro-benzene-sulfonic acid (TNBS)-induced ulcerative colitis (UC) model in rats. METHODS: The synthetic RA-SS-mPEG was characterized with NMR spectroscopy, before preparation of luteolin-coated RA-SS-mPEG polymer micelles. The in vitro characterization and evaluation of the formulation were accomplished, couple with its pharmacokinetic parameters. The levels of PEG2, MDA, CRP and GSH, as well as concentrations of TNF-α, IL1-ß, IL-6 and IL-10 in serum and colon tissue were detected via ELISA kit. The degree of colon injury and inflammation was evaluated via histopathologic examination. RESULTS: L-RSPMs displayed small average droplet size (133.40 ± 4.52 nm), uniformly dispersed (PDI: 0.163 ± 0.011), good stability, slow release and enhanced solubility. We observed 353.28% increase in the relative bioavailability of L-RSPMs compared to free luteolin, while the half-life of the micelle was extended by 6.16h. Compared to model (M) group, luteolin (low and high doses) and L-RSPMs (low and high doses) significantly reduced levels of MDA, PEG2, CRP, TNF-α, IL-6 and IL-1ß in colon tissue and serum of colitic rats but dose dependently increased IL-10 and SOD levels (p < 0.01). Histopathologic examination of colon showed that luteolin (low and high doses) and L-RSPMs (low and high doses) improved colonic inflammation in colitic rats to varying degrees compared to M group. CONCLUSION: L-RSPMs could improve TNBS-induced colon inflammation by enhancing bioavailability, promoting antioxidant effects and regulating cytokine release, which may become a potential agent for UC treatment in clinical settings.
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Colitis Ulcerosa , Polímeros , Ratas , Animales , Interleucina-10/efectos adversos , Micelas , Luteolina/efectos adversos , Interleucina-6/efectos adversos , Factor de Necrosis Tumoral alfa , Disponibilidad Biológica , Colitis Ulcerosa/tratamiento farmacológico , Inflamación , Ácido RosmarínicoRESUMEN
Significant proof suggests an essential role played by the bile microbiota in biliary diseases. This study retrospectively analyzed the differences in biliary microbes among patients with perihilar cholangiocarcinoma (pCCA), distal cholangiocarcinoma (dCCA), pancreatic cancer (PC), and cholelithiasis (CH). Bile samples were obtained from 53 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), and the bile microbiota was analyzed through 16S rRNA gene analysis and next-generation sequencing. Based on the results of linear discriminant analysis effect size (LEfSe), the top three biomarkers for pCCA at the genus level were Pseudomonas, Sphingomonas, and Halomonas; for dCCA were Streptococcus, Prevotella, and Halomonas; and for PC were Pseudomonas, Chloroplast, and Acinetobacter. The top five genera in the pCCA, dCCA, and PC groups showed predictive values with areas under the receiver operating characteristic curves of 91.56%, 95.56%, and 96.59%, respectively. The PICRUSt2 analysis outcomes displayed the diversities of fifteen pathways between the CH and pCCA groups, 22 pathways between the CH and dCCA groups, and eighteen pathways between the CH and PC groups. As this pilot study identified specific microbial bile markers for patients with CH, pCCA, dCCA, and PC, the clinical implications are vast. Further study focusing on distinct bacterial populations in bile will help differentiate biliary diseases.