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.

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.

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.

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.

[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.

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.

The application of enhanced recovery after surgery (ERAS) in chronic rhinosinusitis patients undergoing endoscopic sinus surgery: A systematic review and meta-analysis.

OBJECTIVES: Enhanced recovery after surgery (ERAS) has become extensively practiced and has shown encouraging benefits. Within recent years, ERAS has also been increasingly performed in chronic rhinosinusitis (CRS) patients undergoing endoscopic sinus surgery (ESS). However, the actual efficacy of ERAS in CRS patients undergoing ESS is not completely clear, and the related evidence remains weak. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of ERAS in the perioperative management of CRS patients receiving ESS. METHODS: We searched randomized controlled trials in PubMed, Web of Science, EMBASE, Cochrane CENTRAL, Ovid, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, Wanfang, and VIP Database up to February 2023, to analyze the effectiveness and safety of ERAS in ESS perioperative management of CRS patients. We appraised the methodological quality in the included RCTs using the Cochrane Collaboration tool and assessed the quality of evidence with the Recommendations Assessment, Development and Evaluation (GRADE) tool. Meta-analysis, subgroup analysis, and sensitivity analysis were carried out with the the software Review Manager 5.3 and Stata 12.0. In addition, potential publication bias was detected by Begg's test, Egger's test, and funnel plot test. RESULTS: Twenty-eight studies involving 2636 patients were included within this study. In comparison with the standard care (SC) group, the ERAS group had the advantages in the following aspects: length of stay (MD = -2.50, 95%CI: -3.04 to -1.97), pain scores (MD = -1.07, 95%CI: -1.46 to -0.67), anxiety score (SMD = -2.13, 95%CI: -2.83 to -1.44), depression score (SMD = -2.42, 95%CI: -3.13 to -1.71), hospitalization expenses, and quality of life. At the same time, the ERAS group presented a markedly lower incidence of adverse events in comparison to the SC group, such as overall complications (RR = 0.28, 95%CI:0.20 to 0.41), postoperative nausea and vomiting (RR = 0.33, 95%CI:0.21 to 0.50), facial edema (RR = 0.20, 95%CI:0.11 to 0.38), low back pain (RR = 0.28, 95%CI:0.16 to 0.49), urinary retention (RR = 0.12, 95%CI:0.05 to 0.30) and haemorrhage (RR = 0.19, 95%CI:0.07 to 0.55). CONCLUSIONS: The results showed that the ERAS protocol is effective and safe in CRS patients who undergo ESS. However, Due to the limited overall methodological quality included studies, caution should be exercised in the interpretation of the results. More high-quality, multiple-centre, and large-sample studies are in demand in the future to further validate its clinical efficacy.

Prognostic and clinicopathological role of RACK1 for cancer patients: a systematic review and meta-analysis.

Background: The receptor for activated C kinase 1 (RACK1) expression is associated with clinicopathological characteristics and the prognosis of various cancers; however, the conclusions are controversial. As a result, this study aimed to explore the clinicopathological and prognostic values of RACK1 expression in patients with cancer. Methodology: PubMed, Embase, Web of Science, Cochrane Library, and Scopus were comprehensively explored from their inception to April 20, 2023, for selecting studies on the clinicopathological and prognostic role of RACK1 in patients with cancer that met the criteria for inclusion in this review. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the prognosis-predictive value of RACK1 expression, while pooled odds ratios (ORs) and 95% CIs were used to evaluate the correlation between RACK1 expression and the clinicopathological characteristics of patients with cancer. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Results: Twenty-two studies (13 on prognosis and 20 on clinicopathological characteristics) were included in this systematic review and meta-analysis. The findings indicated that high RACK1 expression was significantly associated with poor overall survival (HR = 1.62; 95% CI, 1.13-2.33; P = 0.009; I2 = 89%) and reversely correlated with disease-free survival/recurrence-free survival (HR = 1.87; 95% CI, 1.22-2.88; P = 0.004; I2 = 0%). Furthermore, increased RACK1 expression was significantly associated with lymphatic invasion/N+ stage (OR = 1.74; 95% CI, 1.04-2.90; P = 0.04; I2 = 79%) of tumors. Conclusions: RACK1 may be a global predictive marker of poor prognosis in patients with cancer and unfavorable clinicopathological characteristics. However, further clinical studies are required to validate these findings.

Association of Fish Oil Supplementation with Risk of Coronary Heart Disease in Individuals with Diabetes and Prediabetes: A Prospective Study in the UK Biobank.

This study aimed to explore the association between habitual intake of fish oil supplementation and the risk of developing CHD in patients with prediabetes and diabetes. Habitual use of fish oil was assessed by repeated questionnaires. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median follow-up of 11.6 years, 4304 and 3294 CHD cases were documented among 47,663 individuals with prediabetes and 22,146 patients with diabetes in the UK Biobank, respectively. After multivariable adjustment, the HRs (95% CI) of CHD were 0.91 (0.85-0.98) and 0.87 (0.80-0.95) for individuals utilizing fish oil supplementation compared with non-users among the participants with prediabetes and diabetes, respectively. Furthermore, we identified an inverse relationship between fish oil use and CHD incidence, which was significantly mediated by serum C-reactive protein (CRP) levels in individuals with prediabetes and by very-low-density lipoprotein cholesterol (VLDL-C) in patients with diabetes at baseline. The inverse associations were consistent in the analyses stratified by potential confounders. In conclusion, the consumption of fish oil supplements was linked to decreased serum CRP and VLDL-C levels and subsequent CHD risk among adults with prediabetes and diabetes. Our findings highlight the important role of the habitual intake of fish oil supplements in preventing CHD in individuals with impaired glucose metabolism.

Androgen receptor knockdown enhances prostate cancer chemosensitivity by down-regulating FEN1 through the ERK/ELK1 signalling pathway.

PURPOSE: Flap endonuclease 1 (FEN1) is highly upregulated in prostate cancer and promotes the growth of prostate cancer cells. Androgen receptor (AR) is the most critical determinant of the occurrence, progression, metastasis, and treatment of prostate cancer. However, the effect of FEN1 on docetaxel (DTX) sensitivity and the regulatory mechanisms of AR on FEN1 expression in prostate cancer need to be further studied. METHODS: Bioinformatics analyses were performed using data from the Cancer Genome Atlas and the Gene Expression Omnibus. Prostate cancer cell lines 22Rv1 and LNCaP were used. FEN1 siRNA, FEN1 overexpression plasmid, and AR siRNA were transfected into cells. Biomarker expression was evaluated by immunohistochemistry and Western blotting. Apoptosis and the cell cycle were explored using flow cytometry analysis. Luciferase reporter assay was performed to verify the target relationship. Xenograft assays were conducted using 22Rv1 cells to evaluate the in vivo conclusions. RESULTS: Overexpression of FEN1 inhibited cell apoptosis and cell cycle arrest in the S phase induced by DTX. AR knockdown enhanced DTX-induced cell apoptosis and cell cycle arrest at the S phase in prostate cancer cells, which was attenuated by FEN1 overexpression. In vivo experiments showed that overexpression of FEN1 significantly increased tumour growth and weakened the inhibitory effect of DTX on prostate tumour growth, while AR knockdown enhance the sensitivity of DTX to prostate tumour. AR knockdown resulted in FEN1, pho-ERK1/2, and pho-ELK1 downregulation, and the luciferase reporter assay confirmed that ELK1 can regulate the transcription of FEN1. CONCLUSION: Collectively, our studies demonstrate that AR knockdown improves the DTX sensitivity of prostate cancer cells by downregulating FEN1 through the ERK/ELK1 signalling pathway.

EVALUATING THE OUTCOMES OF MINIMALLY INVASIVE THERAPY VS SURGERY FOR ORAL MUCOCELES: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Oral mucoceles could be managed with minimally invasive therapy (MIT) or conventional surgery, and both modalities reportedly possess advantages and demerits. This review aims to investigate and compare the postoperative disease recurrence and complications of these interventions with each other. METHODS: Relevant studies were searched in 5 databases (PubMed, Embase, Scopus, Web of Science and Cochrane Library) from inception to December 17, 2022. The pooled relative risks (RRs) with 95% confidence intervals (CIs) of disease recurrence, overall complications, nerve injury and bleeding/hematoma in MIT vs conventional surgery were calculated in meta-analysis. Trial Sequential Analysis (TSA) was performed to confirm our conclusions and assess the need for future trials. RESULTS: Six studies (1 randomized controlled trial and 5 cohort studies) were included for systematic review and meta-analysis. The results showed no significant difference in recurrence between MIT and conventional surgery (RR=0.80; 95% CI, 0.39-1.64; P = .54; I2=17%), and the results of the subgroup analysis were consistent. The incidence of the overall complications (RR=0.15; 95% CI, 0.05-0.47; P = .001; I2=0%) and nerve injury (RR=0.22; 95% CI, 0.06-0.82; P = .02; I2=0%) was significantly lower in MIT than in conventional surgery, but the incidence of bleeding/hematoma presented no significant difference (RR=0.34; 95% CI, 0.06-2.07; P = .24; I2=0%). The results of TSA suggested that the conclusion of MIT significantly reducing the risk of overall complications was stable; and additional clinical trials were need in the future for confirming the conclusions regarding disease recurrence, nerve injury and bleeding/hematoma. CONCLUSIONS: For mucoceles in the oral cavity, MIT is less likely to induce complications (i.e., nerve injury) compared with surgical removal, and the control of disease recurrence is comparable to that of conventional surgery. Therefore, the application of MIT for mucoceles could be a promising alternative to conventional surgery when the latter is not applicable.

The Applications of CRISPR/Cas9 System for Urinary System Tumor.

Tumors of the urinary system include those in the urinary and reproductive systems, of which tumors of the prostate, bladder, and kidney have the highest incidence. In recent years, due to changes in dietary structure, prostate cancer has become the most common type of male genitourinary system cancer. Furthermore, due to tobacco consumption, increases in industrialization, and the age of the population, the incidence of bladder cancer in both males and females in both urban and rural areas, has shown an increasing trend. The incidence and mortality of kidney cancer have also increased and negatively affected the lives and health of all residents. While surgery, radiotherapy, and chemotherapy have greatly improved the cure and survival rates of patients with urinary tumors, we lack methods for early detection and effective long-term treatment. New tools and methods for diagnosis and treatment are thus urgently needed. Recently, CRISPR/Cas9 has become an efficient method to alter the genome in many organisms. It can be used to activate or inhibit gene expression, which greatly facilitates the editing of targeted genes, both in vivo and in vitro. It provides a powerful scientific research tool to analyze the mechanisms of disease occurrence and development and to develop advanced targeted drug delivery. The diagnosis and treatment of human tumors will consequently be improved as this technology will surely accelerate cancer research. In this article, we discuss how CRISPR/Cas9 technology can be used to research and treat genitourinary system tumors will consequently be improved as this technology will surely accelerate cancer research. Here, we review the current applications of CRISPR/Cas9 technology for genitourinary system tumor research and therapy.

Antisense Oligonucleotides Selectively Enter Human-Derived Antibiotic-Resistant Bacteria through Bacterial-Specific ATP-Binding Cassette Sugar Transporter.

Current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic-resistant bacteria. Herein, bacteria-specific ATP-binding cassette (ABC) sugar transporters are leveraged to selectively internalize ASOs by hitchhiking them on α (1-4)-glucosidically linked glucose polymers. Compared with their cell-penetrating peptide counterparts, which are non-specifically engulfed by mammalian and bacterial cells, the presented therapeutics consisting of glucose polymer and antisense peptide nucleic-acid-modified nanoparticles are selectively internalized into the human-derived multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e., 51.6%). The developed strategy allows specific and efficient killing of nearly 100% of the antibiotic-resistant bacteria. Its significant curative efficacy against bacterial keratitis and endophthalmitis is also shown. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.

Camouflage Nanoparticles Enable in Situ Bioluminescence-Driven Optogenetic Therapy of Retinoblastoma.

Optogenetic therapy has emerged as a promising technique for the treatment of ocular diseases; however, most optogenetic tools rely on external blue light to activate the photoswitch, whose relatively strong phototoxicity may induce retinal damage. Herein, we present the demonstration of camouflage nanoparticle-based vectors for in situ bioluminescence-driven optogenetic therapy of retinoblastoma. In biomimetic vectors, the photoreceptor CRY2 and its interacting partner CIB1 plasmid are camouflaged with folic acid ligands and luciferase NanoLuc-modified macrophage membranes. To conduct proof-of-concept research, this study employs a mouse model of retinoblastoma. In comparison to external blue light irradiation, the developed system enables an in situ bioluminescence-activated apoptotic pathway to inhibit tumor growth with greater therapeutic efficacy, resulting in a significant reduction in ocular tumor size. Furthermore, unlike external blue light irradiation, which causes retinal damage and corneal neovascularization, the camouflage nanoparticle-based optogenetic system maintains retinal structural integrity while avoiding corneal neovascularization.