Macrophages in CRSwNP: Do they deserve more attention?

Chronic rhinosinusitis (CRS) represents a heterogeneous disorder primarily characterized by the persistent inflammation of the nasal cavity and paranasal sinuses. The subtype known as chronic rhinosinusitis with nasal polyposis (CRSwNP) is distinguished by a significantly elevated recurrence rate and augmented challenges in the management of nasal polyps. The pathogenesis underlying this subtype remains incompletely understood. Macrophages play a crucial role in mediating the immune system's response to inflammatory stimuli. These cells exhibit remarkable plasticity and heterogeneity, differentiating into either the pro-inflammatory M1 phenotype or the anti-inflammatory and reparative M2 phenotype depending on the surrounding microenvironment. In CRSwNP, macrophages demonstrate reduced production of Interleukin 10 (IL-10), compromised phagocytic activity, and decreased autophagy. Dysregulation of pro-resolving mediators may occur during the inflammatory resolution process, which could potentially hinder the adequate functioning of anti-inflammatory macrophages in facilitating resolution. Collectively, these factors may contribute to the prolonged inflammation observed in CRSwNP. Additionally, macrophages may enhance fibrin cross-linking through the release of factor XIII-A (FAXIII), promoting fibrin deposition and plasma protein retention. Macrophages also modulate vascular permeability by releasing Vascular endothelial growth factor (VEGF). Moreover, they may disrupt the balance between Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs), which favors extracellular matrix (ECM) degradation, edema formation, and pseudocyst development. Accumulating evidence suggests a close association between macrophage infiltration and CRSwNP; however, the precise mechanisms underlying this relationship warrant further investigation. In different subtypes of CRSwNP, different macrophage phenotypic aggregations trigger different types of inflammatory features. Increasing evidence suggests that macrophage infiltration is closely associated with CRSwNP, but the mechanism and the relationship between macrophage typing and CRSwNP endophenotyping remain to be further explored. This review discusses the role of different types of macrophages in the pathogenesis of different types of CRSwNP and their contribution to polyp formation, in the hope that a better understanding of the role of macrophages in specific CRSwNP will contribute to a precise and individualized understanding of the disease.

Synergistic effects of peracetic acid and free ammonia pretreatment on anaerobic fermentation of waste activated sludge to promote short-chain fatty acid production for polyhydroxyalkanoate biosynthesis: Mechanisms and optimization.

Peracetic acid (PAA) combined with free ammonia (FA) pretreatment can be utilized to promote anaerobic fermentation (AF) of waste activated sludge (WAS) to produce short-chain fatty acids (SCFAs), and the resulting SCFAs are desirable carbon sources (C-sources) for polyhydroxyalkanoate (PHA) biosynthesis. This work aimed to determine the optimum conditions for PAA + FA pretreatment of sludge AF and the feasibility of using anaerobic fermentation liquor (AFL) for PHA production. To reveal the mechanisms of integrated pretreatment, the impacts of PAA + FA pretreatment on different stages of sludge AF and changes in the microbial community structure were explored. The experimental results showed that the maximum SCFA yield reached 491.35 ± 6.02 mg COD/g VSS on day 5 after pretreatment with 0.1 g PAA/g VSS +70 mg FA/L, which was significantly greater than that resulting from PAA or FA pretreatment alone. The mechanism analysis showed that PAA + FA pretreatment promoted sludge solubilization but strongly inhibited methanogenesis. According to the analysis of the microbial community, PAA + FA pretreatment changed the microbial community structure and promoted the enrichment of bacteria related to hydrolysis and acidification, and Proteiniclasticum, Macellibacteroides and Petrimonas became the dominant hydrolytic and acidifying bacteria. Finally, after alkali treatment, the AFL was utilized for batch-mode PHA production, and a maximum PHA yield of 55.05 wt% was achieved after five operation periods.

Fruit but not vegetable consumption is beneficial for low prevalence of colorectal polyps in a high-risk population: findings from a Chinese Lanxi Pre-colorectal Cancer Cohort study.

PURPOSE: The available evidence regarding the role of fruit and vegetable consumption in the development of colorectal polyps remains inconclusive, and there is a lack of data on different histopathologic features of polyps. We aimed to evaluate the associations of fruit and vegetable consumption with the prevalence of colorectal polyps and its subtypes in a high-risk population in China. METHODS: We included 6783 Chinese participants aged 40-80 years who were at high risk of colorectal cancer (CRC) in the Lanxi Pre-colorectal Cancer Cohort (LP3C). Dietary information was obtained through a validated food-frequency questionnaire (FFQ), and colonoscopy screening was used to detect colorectal polyps. Dose-response associations of fruit and vegetable intake with the prevalence of polyps were calculated using multivariate-adjusted regression models, which was reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: 2064 cases of colorectal polyps were ascertained in the LP3C during 2018-2019. Upon multivariable adjustments, including the diet quality, fruit consumption was inversely associated with the prevalence of polyps (P trend = 0.02). Participants in the highest tertile of fruit intake had a 25% lower risk (OR: 0.75; 95% CI 0.62‒0.92) compared to non-consumers, while vegetable consumption had no significant association with polyp prevalence (P trend = 0.86). In terms of colorectal histopathology and multiplicity, higher fruit intake was correlated with 24, 23, and 33% lower prevalence of small polyps (OR: 0.76; 95% CI 0.62‒0.94; P trend = 0.05), single polyp (OR: 0.77; 95% CI 0.62‒0.96; P trend = 0.04), and distal colon polyps (OR: 0.67; 95% CI 0.51‒0.87; P trend = 0.003), respectively. CONCLUSIONS: Fresh fruit is suggested as a protective factor to prevent colorectal polyps in individuals at high risk of CRC, and should be underscored in dietary recommendations, particularly for high-risk populations.

Neuroprotective efficacy of hypothermia and Inter-alpha Inhibitor Proteins after hypoxic ischemic brain injury in neonatal rats.

Therapeutic hypothermia is the standard of care for hypoxic-ischemic (HI) encephalopathy. Inter-alpha Inhibitor Proteins (IAIPs) attenuate brain injury after HI in neonatal rats. Human (h) IAIPs (60 â€‹mg/kg) or placebo (PL) were given 15 â€‹min, 24 and 48 â€‹h to postnatal (P) day-7 rats after carotid ligation and 8% oxygen for 90 â€‹min with (30 â€‹°C) and without (36 â€‹°C) exposure to hypothermia 1.5 â€‹h after HI for 3 â€‹h. Hemispheric volume atrophy (P14) and neurobehavioral tests including righting reflex (P8-P10), small open field (P13-P14), and negative geotaxis (P14) were determined. Hemispheric volume atrophy in males was reduced (P â€‹< â€‹0.05) by 41.9% in the normothermic-IAIP and 28.1% in the hypothermic-IAIP compared with the normothermic-PL group, and in females reduced (P â€‹< â€‹0.05) by 30.3% in the normothermic-IAIP, 45.7% in hypothermic-PL, and 55.2% in hypothermic-IAIP compared with the normothermic-PL group after HI. Hypothermia improved (P â€‹< â€‹0.05) the neuroprotective effects of hIAIPs in females. The neuroprotective efficacy of hIAIPs was comparable to hypothermia in female rats (P â€‹= â€‹0.183). Treatment with hIAIPs, hypothermia, and hIAIPs with hypothermia decreased (P â€‹< â€‹0.05) the latency to enter the peripheral zone in the small open field test in males. We conclude that hIAIPs provide neuroprotection from HI brain injury that is comparable to the protection by hypothermia, hypothermia increases the effects of hIAIPs in females, and hIAIPs and hypothermia exhibit some sex-related differential effects.

Framework Nucleic Acids Combined with 3D Hybridization Chain Reaction Amplifiers for Monitoring Multiple Human Tear Cytokines.

Existing tear sensors are difficult to perform multiplexed assays due to the minute amounts of biomolecules in tears and the tiny volume of tears. Herein, the authors leverage DNA tetrahedral frameworks (DTFs) modified on the wireless portable electrodes to effectively capture 3D hybridization chain reaction (HCR) amplifiers for automatic and sensitive monitoring of multiple cytokines in human tears. The developed sensors allow the sensitive determination of various dry eye syndrome (DES)-associated cytokines in human tears with the limit of detection down to 0.1 pg mL-1, consuming as little as 3 mL of tear fluid. Double-blind testing of clinical DES samples using the developed sensor and commercial ELISA shows no significant difference between them. Compared with single-biomarker diagnosis, the diagnostic accuracy of this sensor based on multiple biomarkers has improved by ≈16%. The developed system offers the potential for tear sensors to enable personalized and accurate diagnosis of various ocular diseases.

Thyroid Ultrasound Appropriateness Identification Through Natural Language Processing of Electronic Health Records.

Objective: To address thyroid cancer overdiagnosis, we aim to develop a natural language processing (NLP) algorithm to determine the appropriateness of thyroid ultrasounds (TUS). Patients and Methods: Between 2017 and 2021, we identified 18,000 TUS patients at Mayo Clinic and selected 628 for chart review to create a ground truth dataset based on consensus. We developed a rule-based NLP pipeline to identify TUS as appropriate TUS (aTUS) or inappropriate TUS (iTUS) using patients' clinical notes and additional meta information. In addition, we designed an abbreviated NLP pipeline (aNLP) solely focusing on labels from TUS order requisitions to facilitate deployment at other health care systems. Our dataset was split into a training set of 468 (75%) and a test set of 160 (25%), using the former for rule development and the latter for performance evaluation. Results: There were 449 (95.9%) patients identified as aTUS and 19 (4.06%) as iTUS in the training set; there are 155 (96.88%) patients identified as aTUS and 5 (3.12%) were iTUS in the test set. In the training set, the pipeline achieved a sensitivity of 0.99, specificity of 0.95, and positive predictive value of 1.0 for detecting aTUS. The testing cohort revealed a sensitivity of 0.96, specificity of 0.80, and positive predictive value of 0.99. Similar performance metrics were observed in the aNLP pipeline. Conclusion: The NLP models can accurately identify the appropriateness of a thyroid ultrasound from clinical documentation and order requisition information, a critical initial step toward evaluating the drivers and outcomes of TUS use and subsequent thyroid cancer overdiagnosis.

Parental Autonomy Granting, Peer Attachment and Problematic Internet Use Among Chinese Adolescents: The Moderating Effect of School Climate.

While the correlation between parental autonomy granting and adolescents' problematic Internet use (PIU) has been confirmed, the processes underlying this connection have not been thoroughly investigated. Drawing on the ecological systems theory, this study sought to investigate the mediating mechanism of peer attachment and the moderating mechanism of school climate that link parental autonomy granting to PIU. A two-wave longitudinal design was employed with a time interval of six months. The participants were 852 adolescents who attended three middle schools located in Guangdong Province, China. Self-report questionnaires were used to obtain data on demographics, parental autonomy granting, peer attachment, school climate, and PIU. The findings indicated that peer attachment significantly mediated the link between parental autonomy granting and adolescent PIU. A positive school climate significantly moderated the influence of parental autonomy granting on peer attachment and the influence of peer attachment on PIU. Specifically, the association between parental autonomy granting and peer attachment and the association between peer attachment and PIU were more pronounced when the school climate was perceived to be positive. This research underscores the possible significance of peer attachment in the association between parental autonomy granting and PIU and offers valuable insights for mitigating the negative outcomes of PIU.

Prevalence and predictors of depression and anxiety in patients with chronic rhinosinusitis: a systematic review and meta-analysis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a persistent inflammation of the sinuses. As a result of long-term discomfort, patients may experience symptoms of common mental disorders such as anxiety and depression. This may affect the quality of life and disease progression. However, there is still uncertainty about the extent of the problem. OBJECTIVE: This meta-analysis aimed to determine the prevalence of depression and anxiety symptoms in patients with CRS. SEARCH STRATEGY: We searched PubMed, Embase, Web of Science, Cochrane Library, and CBM databases for relevant studies published before 15 July 2022 in patients with CRS with concomitant depression and anxiety symptoms. DATA COLLECTION AND ANALYSIS: Two authors independently performed screening and quality assessment using validated tools. Extraction of data using predefined standardised data collection spreadsheets. Heterogeneity and inconsistency were checked using the I² statistic. RESULTS: The meta-analysis included 32 articles involving 56 933 patients. The prevalence of depression and anxiety symptoms was estimated at 24.7% (95% CI, 21.3% to 28. 1%) and 29.7% (95% CI, 19.3% to 40.2%). Subgroup analysis revealed the following: (1) CRS without nasal polyps (CRSsNP): 26.2% (95% CI, 21.9% to 30.5%), CRS with nasal polyps(CRSwNP): 20% (95% CI, 15.9% to 24%); (2) Female patients: 36. 1% (95% CI, 25.3% to 46.9%), male patients: 24.3% (95% CI, 12. 1% to 36.6%); and (3) The average age≤50 years patients: 29.8% (95% CI, 21.3% to 38.2%), the average age>50 years patients: 22. 1% (95% CI, 17.1% to 27%). CONCLUSION: A significant proportion of people with CRS have symptoms of depression and anxiety, and early screening for depression and anxiety in people with CRS is critical. And, more attention needs to be given to females and patients with CRSsNP during screening. PROSPERO REGISTRATION NUMBER: CRD42022345959).

Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature.

BACKGROUND: Collision tumors involving the small intestine, specifically the combination of a hamartomatous tumor and a lipoma, are extremely rare. To our knowledge, no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine. CASE SUMMARY: Here, we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm × 32 mm × 30 mm in the terminal ileum. Based on computed tomography scan findings, the mass was initially suspected to be a lipoma. A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line. A biopsy of the upper portion suggested a juvenile polyp (JP). Owing to the patient's advanced age, multiple comorbidities, and poor surgical tolerance, a modified endoscopic submucosal dissection was performed. Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top, demonstrating evidence of rupture and associated bleeding. The patient's overall health remained satisfactory, with no recurrence of hematochezia during the six-month follow-up period. CONCLUSION: This case report provides new evidence for the understanding of gastrointestinal collision tumors, emphasizing their diverse clinical presentations and histopathological characteristics. It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

Clinical learning environment for nursing students in operating rooms: Development of an evaluation scale.

Aim: To develop a measurement tool to evaluate the clinical learning environment for nursing students in operating rooms. Background: In this study, a scale for evaluating the clinical learning environment for nursing students in operating rooms was developed and subjected to reliability and validity tests. Design: A cross-sectional, methodological study. Methods: Qualitative interviews, the Delphi method, a literature review and pilot testing were employed to develop the scale. A purposive sampling method was used to select September 2021 through May 2022; a total of 227 nursing students with internship experience in operating rooms at several teaching hospitals in North China were selected to evaluate the reliability and validity of the scale. Results: The 32-item, four-dimensional evaluation scale was developed through two rounds of consultation with 17 experts. The reliability and validity test showed that the overall Cronbach's alpha was 0.984 and 0.96. The split-half reliability for the total scale was 0.937, indicating good reliability. Conclusion: The proposed scale has high reliability and validity in evaluating the clinical learning environment of nursing students in operating rooms and improving clinical nursing education.

[Systematic review and Meta-analysis of efficacy and safety of Bidouyan Oral Liquid in treatment of rhinosinusitis].

This study aimed to systematically review the efficacy and safety of Bidouyan Oral Liquid in the treatment of rhinosinu-sitis(RS). CNKI, Wanfang, SinoMed, VIP, Cochrane Library, PubMed, EMbase, Web of Science, and Ovid were searched for the randomized controlled trial(RCT) of Bidouyan Oral Liquid for the treatment of RS patients. Moreover, the reference lists and the grey literature were searched manually. Two researchers independently screened the literature and extracted data. The Cochrane collaboration's tool for assessing risk of bias(RoB 2.0) in randomized trial was used to assess the methodological quality of the included stu-dies. Meta-analysis was performed in RevMan 5.3 and Stata 12.0, and the grades of recommendation, assessment, development and evaluation(GRADE) was employed to evaluate the quality of evidence. A total of 54 RCTs(35 with drug combinations and 19 with single drugs) comprising 7 511 patients(3 973 in the observation group and 3 538 in the control group) were included. Meta-analysis showed that Bidouyan Oral Liquid + conventional treatment was superior to conventional treatment alone in increasing the total response rate(RR=1.19, 95%CI[1.15, 1.24], P<0.000 01) and decreasing the Lund-Kennedy scores(MD=-1.94, 95%CI[-2.61,-1.26], P<0.000 01), Lund-Mackay scores(MD=-2.14, 95%CI[-2.98,-1.31], P<0.000 01), and visual analogue scale(VAS) scores(MD_(total VAS scores)=-1.28, 95%CI[-1.56,-1.01], P<0.000 01; MD_(nasal congestion VAS scores)=-0.58, 95%CI[-0.89,-0.27], P=0.000 2; MD_(runny nose VAS scores)=-0.61, 95%CI[-0.93,-0.29], P=0.000 2; MD_(olfactory dysfunction VAS scores)=-0.43, 95%CI[-0.52,-0.34], P<0.000 01; MD_(head and facial pain VAS scores)=-0.41, 95%CI[-0.57,-0.26], P<0.000 01). Furthermore, the combined treatment outperformed conventional treatment alone in improving the mucociliary transport rate(MTR)(MD=1.64, 95%CI[1.08, 2.20], P<0.000 01) and lowering the levels of inflammatory cytokines{tumor necrosis factor-α(TNF-α)(SMD=-1.95, 95%CI[-2.57,-1.33], P<0.000 01), interleukin-6(IL-6)(SMD=-2.64, 95%CI[-4.08,-1.21], P=0.000 3)} in RS patients. In addition, the combined treatment did not increase the incidence of adverse reactions(RR=0.83, 95%CI[0.44, 1.57], P=0.57). Bidouyan Oral Liquid was superior to conventional treatment in increasing total response rate(RR=1.25, 95%CI[1.18, 1.32], P<0.000 01), decreasing the Lund-Kennedy(P<0.01) and Lund-Mackay scores(P<0.05), alleviating major symptoms(P_(total VAS scores)<0.01; P_(nasal congestion VAS scores)<0.01; P_(runny nose VAS scores)<0.01; P_(olfactory dysfunction VAS scores)<0.05; P_(head and facial pain VAS scores)<0.01), and decreasing adverse reactions(P=0.03). The results showed that either Bidouyan Oral Liquid or Bidouyan Oral Liquid + conventional treatment can increase the total response rate, decrease the Lund-Kennedy and Lund-Mackay scores, and mitigate major symptoms. In addition, Bidouyan Oral Liquid + conventional treatment improved MTR and reduced the expression of TNF-α and IL-6 without causing serious adverse events. However, due to the limited methodological quality of the included studies, large-sample and high-quality RCTs are needed to provide evidence support.

Fish oil supplementation and risk of dementia among diabetic patients: a prospective study of 16,061 older patients.

BACKGROUND: Although n-3 Polyunsaturated fatty acids (PUFAs) may benefit cognitive performance, the association of n-3 PUFA intake with dementia risk under dysglycemia has not been examined. We aimed to evaluate the relationship between fish oil supplement use or fish consumption and dementia risk among older patients with diabetes. METHOD: A total of 16,061 diabetic patients aged over 60 years were followed up in the UK Biobank. Fish oil supplements use (yes or no) was collected by the touch screen questionnaire. The diagnosis of dementia was ascertained by the UK Biobank Outcome Adjudication Group. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: A total of 337 cases of dementia were confirmed after a mean duration of 7.7 years (123,486 person-years) of follow-up. Habitual use of fish oil supplements showed a 24% lower dementia risk among older diabetic patients [HRs (95% CIs): 0.76 (0.60-0.98) (P = 0.031)] compared with non-users. Such inverse association was not modified by the APOE ε4 genotype. However, the consumption of both oily fish (≥2 times/week) and non-oily fish (≥2 times/week) had no significant association with dementia risk (p-trend = 0.271 and p-trend = 0.065) compared with non-consumers. CONCLUSION: In summary, fish oil supplementation may play a protective role in cognitive function across all APOE genotypes, while non-oily fish and oily fish consumption have no protective association among older diabetic patients.

Prediction and verification of the prognostic biomarker SLC2A2 and its association with immune infiltration in gastric cancer.

Gastric cancer (GC) is the fifth most common cause of cancer-associated deaths; however, its treatment options are limited. Despite clinical improvements, chemotherapy resistance and metastasis are major challenges in improving the prognosis and quality of life of patients with GC. Therefore, effective prognostic biomarkers and targets associated with immunological interventions need to be identified. Solute carrier family 2 member 2 (SLC2A2) may serve a role in tumor development and invasion. The present study aimed to evaluate SLC2A2 as a prospective prognostic marker and chemotherapeutic target for GC. SLC2A2 expression in several types of cancer and GC was analyzed using online databases, and the effects of SLC2A2 expression on survival prognosis in GC were investigated. Clinicopathological parameters were examined to explore the association between SLC2A2 expression and overall survival (OS). Associations between SLC2A2 expression and immune infiltration, immune checkpoints and IC50 were estimated using quantification of the tumor immune contexture from human RNA-seq data, the Tumor Immune Estimation Resource 2.0 database and the Genomics of Drug Sensitivity in Cancer database. Differential SLC2A2 expression and the predictive value were validated using the Human Protein Atlas, Gene Expression Omnibus, immunohistochemistry and reverse transcription-quantitative PCR. SLC2A2 expression was downregulated in most types of tumor but upregulated in GC. Functional enrichment analysis revealed an association between SLC2A2 expression and lipid metabolism and the tumor immune microenvironment. According to Gene Ontology term functional enrichment analysis, SLC2A2-related differentially expressed genes were enriched predominantly in 'chylomicron assembly', 'plasma lipoprotein particle assembly', 'high-density lipoprotein particle', 'chylomicron', 'triglyceride-rich plasma lipoprotein particle', 'very-low-density lipoprotein particle'. 'intermembrane lipid transfer activity', 'lipoprotein particle receptor binding', 'cholesterol transporter activity' and 'intermembrane cholesterol transfer activity'. In addition, 'cholesterol metabolism', and 'fat digestion and absorption' were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Patients with GC with high SLC2A2 expression had higher levels of neutrophil and M2 macrophage infiltration and a significant inverse correlation was observed between SLC2A2 expression and MYC targets, tumor mutation burden, microsatellite instability and immune checkpoints. Furthermore, patients with high SLC2A2 expression had worse prognosis, including OS, disease-specific survival and progression-free interval. Multivariate regression analysis demonstrated that SLC2A2 could independently prognosticate GC and the nomogram model showed favorable performance for survival prediction. SLC2A2 may be a prospective prognostic marker for GC. The prediction model may improve the prognosis of patients with GC in clinical practice, and SLC2A2 may serve as a novel therapeutic target to provide immunotherapy plans for GC.

Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis.

OBJECTIVE: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible. RESULTS: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A1c and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A1c concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration. CONCLUSIONS: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A1c and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022342845.

Development of nanobodies specific to clumping factors A of Staphylococcus aureus by yeast surface display.

The Staphylococcus aureus clumping factor A (ClfA) is a fibrinogen (Fg) binding protein that plays an important role in the clumping of S. aureus in blood plasma. The current anti-infective approaches targeting ClfA are mainly based on monoclonal antibodies but showed less impressive efficacy for clinical applications. Nanobodies offer advantages in enhanced tissue penetration and a propensity to bind small epitopes. However, there is no report on generating specific nanobodies for ClfA. Here, we constructed a synthetic nanobody library based on yeast surface display to isolate nanobodies against the Fg binding domain ClfA221-550. We firstly obtained a primary nanobody directed to ClfA221-550, and then employed error-prone mutagenesis to enhance its binding affinity. Finally, 18 variants were isolated with high affinities (EC50, 1.1 ± 0.1 nM to 4.8 ± 0.3 nM), in which CNb1 presented the highest inhibition efficiency in the adhesion of S. aureus to fibrinogen. Moreover, structural simulation analysis indicated that the epitope for CNb1 partially overlapped with the binding sites for fibrinogen, thus inhibiting ClfA binding to Fg. Overall, these results indicated that the specific nanobodies generated here could prevent the adhesion of S. aureus to fibrinogen, suggesting their potential capacities in the control of S. aureus infections.

Prevalence and influencing factors of sleep disorders in patients with CRS: a protocol for systematic review and meta-analysis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common chronic disease that seriously affects patients' quality of life and imposes a heavy physical and mental burden on patients. There is growing evidence that sleep disorders are strongly associated with patients with CRS. However, there is no systematic evidence to clarify the prevalence and influencing factors of sleep disorders in patients with CRS with nasal polyps (NP) (CRSwNP) and CRS without NP (CRSsNP). For this reason, this study will systematically analyse the prevalence of sleep disorders in patients with CRSwNP and CRSsNP and explore the related influencing factors. METHODS AND ANALYSIS: We will electronically search PubMed, Web of Science, Embase, Cochrane, Ovid, Scopus, the China National Knowledge Infrastructure, the Wanfang database, the China Biomedical Literature Database and the China Scientific Journals Database from the establishment of the database to September 2023 to collect the prevalence of sleep disorders in patients with CRSwNP or CRSsNP and related studies on factors affecting sleep disorders. Two researchers will independently conduct literature screening and data extraction and evaluate the quality of the included studies using the Newcastle-Ottawa Quality Scale and Agency for Healthcare Research and Quality scales. The extracted data will be meta-analysed using Review Manager 5.3 and Stata 14.0 software, and the quality of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation. Publication bias will be assessed using the funnel plots, Egger's test and Begg's test. ETHICS AND DISSEMINATION: This review will not require ethical approval, as we will only use research data from the published documents. Our final findings will be published in a peer-reviewed, open-access journal for dissemination. PROSPERO REGISTRATION NUMBER: CRD42023446833.

Significant dysregulation of lipid metabolism in patients with papillary thyroid carcinoma after thyroidectomy.

Introduction: Thyroidectomy and thyrotropin suppressive therapy is the widely used surgical treatment for papillary thyroid carcinoma (PTC) patients. However, systematic metabolic changes of post-operative PTC patients were rarely reported. Methods: Here, untargeted metabolomic detection of cohorts from PTC before (t0) and 1-month-after (t1) thyroidectomy, were performed to characterize circulating metabolic signatures after surgical treatment. Results: Our results showed PTC patients exhibited lower thyroid stimulating hormone degree, higher total thyroxine, and significant lipid-related metabolic alternations after thyroidectomy, which included 97 upregulations (including 93 lipids) and 5 downregulations (including 2 lipids and 3 nucleotides). Enrichment of metabolic pathways mainly included biosynthesis of fatty acids, purine metabolism, and linoleic acid metabolism. We also demonstrated that differential surgical approaches (hemi- and total thyroidectomy) and post-operative complication phenotypes (insomnia, fatigue), might lead to characteristic metabolic signatures. Discussion: This study revealed dynamic changes of metabolite characteristics of PTC patients after surgical treatment, which were associated with clinical thyroid function parameters, surgical approaches, and complication occurrence. It enlightened us to pay more attention on the post-operative metabolic dysregulation of PTC patients and their long-term qualities of life, so as to provide cautious clinical decisions on surgical choices, treatments, and follow-up details.

Quinolines: A Promising Heterocyclic Scaffold for Cancer Therapeutics.

The quinoline scaffold is a widely recognized heterocycle with applications across various disease categories, ranging from malaria and viral infections to bacterial infections, high cholesterol, and even tumors. Consequently, quinoline plays a crucial role in the development of new drugs, and the field greatly benefits from advancements in computer-aided drug design. This review aims to provide insights into the evolution of quinoline and its derivatives, offering a comprehensive exploration of both marketed and developing drugs. Furthermore, the function and mechanism of quinoline compounds are introduced. Many studies rely on cell experiments to demonstrate drug cytotoxicity. In the concluding section of this review, the interaction between quinoline compounds and targets is simulated using computer-aided drug design methods. A thorough analysis is conducted on the potential influencing factors affecting the binding state between quinoline compounds and targets. Notably, the Pi-Alkyl interaction emerges as a significant contributor, while hydrogen bonding is identified as a pivotal bond in these interactions. This review serves as a valuable overview of the potential contributions of quinoline compounds to cancer treatment. It seamlessly combines the essential functions of marketed quinoline drugs with the promise held by emerging quinoline-based compounds. Additionally, the simulation of interactions between quinoline compounds and proteins through computer-aided design enhances our understanding of these compounds' efficacy.

Circulating fatty acids, genetic risk, and incident coronary artery disease: A prospective, longitudinal cohort study.

The role of fatty acids (FAs) in primary prevention of coronary artery disease (CAD) is highly debated, and the modification effect by genetic risk profiles remains unclear. Here, we report the prospective associations of circulating FAs and genetic predisposition with CAD development in 101,367 U.K. Biobank participants. A total of 3719 CAD cases occurred during a mean follow-up of 11.5 years. Plasma monounsaturated FAs (MUFAs) were positively associated with risk of CAD, whereas the risk was significantly lower with higher n-3 polyunsaturated FAs (PUFAs) and more reductions in risk were detected among TT carriers of rs174547. Furthermore, increased plasma saturated FAs (SFAs) and linoleic acid were related to a significant increase in CAD risk among participants with high genetic risk (genetic risk score > 90%). These findings suggest that individuals with high genetic risk need to reduce plasma SFAs levels for CAD prevention. Supplementation of n-3 PUFAs for CAD prevention may consider individuals' genetic makeup.