Background:Severe coronary anatomical involvement is clinically important in patients with acute coronary syndrome (ACS), yet evidence on its relationship with insulin sensitivity remains limited. This study examined the association of the single-point insulin sensitivity estimator (SPISE), a simple surrogate marker of insulin sensitivity, with severe coronary anatomical patterns, including left main and/or three-vessel disease and isolated three-vessel disease, in middle-aged and older patients with ACS. Methods:This cross-sectional analysis was based on data from the CCC-ACS project. A total of 16,383 patients were included in the analysis of left main and/or three-vessel disease, and 13,390 patients were included in the analysis of isolated three-vessel disease. SPISE was analyzed as both a continuous variable and according to tertiles. Multivariable logistic regression was used to evaluate the associations between SPISE and the study outcomes. Restricted cubic spline analyses were performed to assess dose-response patterns, and subgroup and sensitivity analyses were conducted to examine the robustness of the findings. Results:Higher SPISE was associated with lower odds of both severe coronary anatomical outcomes. In the fully adjusted model, each 1-unit increase in SPISE was associated with lower odds of left main and/or three-vessel disease (OR, 0.977; 95% CI, 0.957-0.998) and isolated three-vessel disease (OR, 0.957; 95% CI, 0.935-0.980). Compared with patients in the lowest SPISE tertile, those in the highest tertile had lower odds of both outcomes. Restricted cubic spline analyses supported dose-response relationships. Subgroup analyses suggested age-related heterogeneity, with the inverse associations mainly observed in patients aged <65 years and attenuated among those aged ≥65 years. Sensitivity analyses yielded generally consistent results. Conclusion:Among ACS patients aged 45 years or older, higher SPISE was associated with lower odds of severe coronary anatomical involvement, with this association mainly evident in patients aged <65 years. These findings support a potential link between reduced insulin sensitivity and angiographically defined severe coronary anatomical involvement and suggest that SPISE may serve as a readily available marker for identifying patients more likely to have high-risk coronary anatomy.

Purpose:Left ventricular hypertrophy (LVH) represents the most common form of target-organ damage in pediatric primary hypertension, yet accessible biomarkers associated with early cardiac remodeling remain poorly characterized. This study investigated whether platelet distribution width (PDW), a routinely available platelet index, is associated with LVH in children with primary hypertension using an adiposity-matched design and evaluated its incremental predictive value beyond conventional clinical factors. Methods: We conducted a 1:1 matched case–control study including 126 treatment-naïve children with primary hypertension (63 matched pairs). Patients with echocardiographic LVH were matched to controls by age, sex, and body mass index. Conditional logistic regression was used to evaluate the association between PDW and LVH after adjustment for visceral adiposity index, obstructive sleep apnea syndrome, and hypertension grade. Incremental predictive value was assessed using receiver-operating characteristic analysis and reclassification metrics. Results: Despite comparable body mass index, PDW was significantly higher in children with LVH than in matched controls (12.22 ±1.44 vs. 11.13 ±1.18 fL, P < 0.001). PDW showed modest discrimination for LVH (AUC = 0.696). After multivariable adjustment, PDW remained independently associated with LVH (odds ratio 1.53, 95% confidence interval 1.09–2.13; P = 0.013). Addition of PDW to the clinical base model improved discrimination (AUC 0.703 to 0.791; ΔAUC 0.087, 95% CI 0.022–0.152) and risk reclassification (continuous NRI = 0.603). Conclusion: PDW independently predicts LVH and enhances risk stratification in pediatric hypertension.

The aim of this study was to establish body surface area (BSA)-dependent Z-score continuous reference intervals of coronary artery diameter measured by Echocardiography in healthy Chinese children population. Echocardiography measured 1221 healthy Chinese children’s coronary artery diameters, including the LMCA, LAD, LCX, RCA-pro, RCA-mid, and RCA-dis. We employed the LMS (Lambda-Mu-Sigma) method for the model and the Haycock equation for the BSA estimation. The coronary artery diameter Z-score continuous reference intervals were established using the LMS method and passed the internal and external validation. Conclusions: The study outcome provides BSA-dependent Z-score continuous reference intervals for the coronary artery diameters in healthy Chinese children. There is a web Z-score calculator with convenient application for clinicians and ultrasound doctors, facilitating subsequent external validations in a larger population.

BackgroundCoronary artery calcification (CAC) is an important indicator of atherosclerosis in the coronary arteries, the degree of which is closely associated with the risk for cardiovascular events. Angiopoietin-like protein 4 (ANGPTL4) plays a significant part in lipid metabolism and energy balance, and may also participate in the progression of CAC. This study was designed to examine the association between ANGPTL4 and CAC and to develop a nomogram to predict the risk of severe CAC.MethodsA total of 600 individuals who underwent multi-slice computed tomography (CT) of the coronary arteries and had available Agatston coronary artery calcification scores (CACS) at Beijing Anzhen Hospital were enrolled. Participants were divided into two groups: those with non-severe CAC (CACS ≤ 400) and those with severe CAC (CACS > 400). Determination of ANGPTL4 levels using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. Identifying variables independently associated with severe CAC through least absolutely shrinkage selection operator (LASSO) regression analysis and logistic regression analysis.ResultsSerum ANGPTL4 levels exhibited significantly higher concentrations in patients with severe CAC compared to those with non-severe CAC (p = 0.007). ANGPTL4 levels were positively associated with CAC severity, independent of other clinical risk factors. Age, smoking status, statin use, glycated hemoglobin A1c (HbA1c), serum phosphate, and ANGPTL4 were included in the predictive model for severe CAC. Receiver operating characteristic (ROC) curve analytics indicate that this model demonstrates acceptable discriminatory ability for severe CAC, with an area under the curve (AUC) of 0.708 [95% confidence interval (CI): 0.649–0.767].ConclusionsThis study indicates that ANGPTL4 is independently associated with severe CAC, suggesting that ANGPTL4 could serve as a candidate biomarker and treatment target for vascular calcification.

Circadian syndrome (CircS) is more predictive than metabolic syndrome (MetS). However, few studies have examined its risk factor. This study aims to investigate whether the static state or dynamic change of frailty is correlated with incident CircS in Chinese adults. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). Baseline frailty was evaluated by frailty index (FI) and frailty status: frail (FI ≥ 0.25), pre-frail (0.10 < FI < 0.25), and robust (FI ≤ 0.10). Changes in frailty were assessed through changes in frailty status, total FI, delta FI and K-means clustering classifications. CircS was defined as the presence of at least 4 of 7 components (MetS components plus depression and short sleep duration). Restricted cubic splines (RCS) and logistic regression models were utilized to assess the association of baseline frailty or its alterations with CircS incidence after adjusting for potential confounders. A total of 5,042 and 3,527 participants were included in baseline and dynamic analyses, respectively. Compared with stable robust participants, those who transitioned from robust to pre-frail/frail status exhibited increased CircS risk (OR: 1.38, 95

Background Over-activated M1 macrophages, which destroyed the balance of macrophage phenotype in the synovial microenvironment, play a pivotal role in rheumatoid arthritis (RA) progression. Increasing evidence indicates that m6A RNA methylation serves as a crucial epigenetic regulatory mechanism in modulating the transition from M0 to M1 macrophages. Saposhnikovia divaricata (Turcz.) Schischk treats RA through immune regulation. In our previous study, chromones (CHR) from Saposhnikovia divaricata could alleviate RA by inhibiting the pathological manifestations of synovial inflammation, but the mechanism of action remains to be elucidated. Purpose To elucidate the pharmacology and mechanism of CHR on m6A RNA methylation mediated M1 macrophages for RA treatment. Methods In CIA mice, joint inflammation was assessed clinically and histologically, while bone changes were quantified by micro-CT and H&E staining. In vitro, the effects of CHR on macrophage polarization were analyzed by examining cell surface proteins, effector cytokine secretion, and master transcription factor expression. Target determination was interrogated through dot blot combined with the GEO database, corroborated by the sgRNA of CBLL1. Downstream mechanistic pathway validation mainly included quantification of expression via RIP-qPCR, CETSA, and DARTS. A co-culture system of MH7A and polarized THP-1 cells was utilized to assess synovial inflammation. Results CHR relieved paw swelling and joint damage and regulated macrophage polarization in CIA mice. Moreover, polarized macrophages were significantly repressed. CHR also modulated the expression of M1 macrophage-associated proteins to influence abnormal characteristics of synovial inflammation. Furthermore, CHR could directly bind to CBLL1 and inhibit its expression and function in macrophages. By knocking down CBLL1, CHR might be involved in regulating macrophage polarization by modulating CBLL1-mediated STAT1/NF-κB expression. Conclusion CHR could inhibit M1 macrophage polarization by regulating CBLL1-mediated m6A RNA methylation to treat RA.

Background and aim This study investigated the associations of Lipoprotein (a) [Lp(a)] and metabolic dysfunction-associated steatotic liver disease (MASLD) with carotid atherosclerosis (CAS) risk, both independently and in combination. Methods and results We performed a multicenter cross-sectional study in participants without cardiovascular disease (CVD) (study 1, n= 61,139) and a longitudinal study in participants without CVD and CAS at baseline who underwent at least two health check-up exams with carotid ultrasound (study 2, n=9,720). Hepatic steatosis and liver fibrosis were assessed via abdominal ultrasonography and the fibrosis-4 (FIB-4) index, respectively. In study 1, among participants without MASLD, those with elevated Lp(a) (≥30 mg/dL) had a significantly higher risk of CAS as compared to those with Lp(a) <30 mg/dL. During a median follow-up of 33 months in Study 2, 2,309 (23.76%) of 9,720 participants progressed to CAS. Baseline Lp(a) ≥30mg/dL (adjusted HR=1.67, 95% CI 1.52-1.83, P<0.001) and MASLD (adjusted HR=1.21, 95% CI 1.09-1.33, P<0.001) were independent risk factors for CAS. In the stratified analysis, a joint effect of Lp(a) ≥30mg/dL and MASLD on CAS risk was observed. Those with Lp(a) (≥30mg/dL) and MASLD had a HR (95% CI) of 2.07 (1.76-2.43, P<0.001) compared to those with Lp(a) <30mg/dL without MASLD, but there was no interaction (Pinteraction = 0.453). Meanwhile, the risk of CAS in participants with Lp(a) ≥30mg/dL and FIB-4 ≥1.3 was 2.62 times higher than Lp(a) <30mg/dL and FIB-4<1.3. Conclusions The combination of elevated Lp(a) and MASLD conferred a greater risk of CAS than either factor alone, demonstrating a joint cardiovascular risk profile.

ETHNOPHARMACOLOGICAL RELEVANCE:Saposhnikovia divaricata (Turcz.) Schisck., a traditional Chinese medicine (TCM), has historically been utilized in the clinical treatment of RA. It was initially documented in the 'Shennong Ben Cao Jing' as a superior quality, with the text stating: 'The herb is widely renowned for its efficacy in alleviating whole-body discomfort, bone pain, malaise, and promoting long-lasting vitality. Chromones (CHR) were identified as the primary active components in Saposhnikovia divaricata. However, the specific molecular mechanisms by which CHR impacts RA remain incompletely understood. AIM OF THE STUDY:To explore the therapeutic efficacy of CHR, a class of compound derived from Saposhnikovia divaricata, in alleviating arthropathy and immune hyperactivity in a collagen-induced arthritis (CIA) mouse model. MATERIAL AND METHODS:Surface plasmon resonance (SPR) molecular fishing and UHPLC-QTOF/MS technology were used to identify CHR in Saposhnikovia divaricata as an active ingredient for treating RA. A CIA mouse model was used to verify the anti-RA effect of CHR in vivo. The anti-RA efficacy of CHR in vivo was evaluated by body weight change, joint swelling, arthritis index, immune organ index, ankle joint disease, and immunoglobulin G (IgG) content. The mechanism of improving RA was further analyzed by a protein chip assay and verified by Western blotting. RESULTS:CHR treatment reduced swelling, arthritis index, and IgG, IgG1, IgG2a, and IgG2b levels in CIA mice. Protein microarray indicated that CHR mitigated CIA-induced joint inflammation by inhibiting immune cell activation, reducing the expression of inflammatory factors and chemokines, potentially by modulating the rheumatoid arthritis pathway involving tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and chemokines. This hypothesis was supported by the upregulation of bone morphogenetic proteins 3 (BMP3) and phospho-Smad2 (p-Smad2) proteins, coupled with the downregulation of interleukin-6 (IL-6), interleukin-1β (IL-1β), TNF-α, and IL-17A proteins in the joints of CHR-treated mice. CONCLUSION:CHR shows promise as a potential therapeutic agent for RA, exerting its effects through anti-inflammatory mechanisms.

A newly identified phenylpropanoid glycoside, calceolarioside F (1), together with twenty known compounds, including nine phenylpropanoids (2-10), eight flavonoids (11-18), and three chromones (19-21), were obtained and identified from the aerial parts of Saposhnikovia divaricata (Turcz.) Schischk. Calceolarioside F (1) was structurally identified through spectroscopic data analysis, including IR, UV, CD, ECD, HR-ESI-MS, and various NMR techniques such as (1D NMR and NOESY, HMBC, 1H-1H COSY, and HSQC), as well as by comparisons with literature data. According to the current research, this was the first instance of isolating compounds (2-18) from Saposhnikovia. In addition, the chemotaxonomic importance of the isolates was discussed.

Prognostic significance of stress hyperglycemia ratio (SHR) has not been well studied in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndromes (ACS). We prospectively measured admission fasting blood glucose (AFBG) and glycated hemoglobin A1c (HbA1c), and retrospectively calculated the stress hyperglycemia ratio (SHR, = AFBG/[1.59 × HbA1c (

Background:Patients without any standard modifiable cardiovascular risk factors (SMuRF-less) who develop acute coronary syndrome (ACS), tend to have poor outcomes. However, the prognostic value of atherogenic index of plasma (AIP) in these patients is unclear. Therefore, we investigated the association between AIP and adverse outcomes in SMuRF-less patients with ACS. Methods:This study retrospectively enrolled 722 SMuRF-less patients with ACS receiving percutaneous coronary intervention (PCI) at Beijing Anzhen Hospital from March 2017 to March 2018. Three patient-groups were formed using AIP tertiles. The primary outcome, major adverse cardiovascular and cerebrovascular events (MACCE), was a composite of all-cause mortality, non-fatal myocardial infarction (MI), unplanned revascularization, and non-fatal ischemic stroke. Association between AIP levels and MACCE risk was examined using restricted cubic spline (RCS) analysis. Prognostic value of AIP levels for MACCE was assessed using multivariable Cox regression models and machine learning approaches. Results:During follow-up of the 722 patients (median age, 60 years [interquartile range, 53-67]; female, 29.8%; median follow-up duration, 59 months), 168 (23.3%) developed MACCE. The RCS results showed linear association of progressively increasing MACCE risk with increasing AIP levels. In multivariable Cox regression analysis, significantly higher MACCE risk occurred with the highest AIP tertile than with the lowest (hazard ratio [HR] 2.03, 95% confidence interval [CI]: 1.34-3.08; P < 0.001). Elevated AIP level was associated with higher risks of all-cause death (HR: 3.49, 95% CI: 1.09-11.23; P = 0.036); non-fatal MI (HR: 3.02, 95% CI: 1.08-8.48; P = 0.035); and unplanned revascularization (HR: 2.18, 95% CI: 1.34-3.52; P < 0.001). As a continuous variable, higher AIP levels were significantly associated with increased risks of MACCE (HR: 2.95, 95% CI: 1.74-4.98; P < 0.001), all-cause mortality (HR: 6.80, 95% CI: 1.85-24.96; P = 0.003), non-fatal myocardial infarction (HR: 3.58, 95% CI: 1.08-11.86; P = 0.037), and unplanned revascularization (HR: 2.84, 95% CI: 1.55-5.19; P < 0.001). Machine-learning models incorporating AIP levels improved outcome prediction. At 48 months, the gradient boosting machine model achieved the highest AUC (0.796; 95% CI: 0.703-0.889), while complementary assessments showed that the random survival forest model provided the greatest net clinical benefit and demonstrated excellent calibration. Conclusion:Among SMuRF-less patients with ACS undergoing PCI, AIP level was identified as an independent predictor of clinical prognosis.

The phytochemical investigation of Saposhnikovia divaricata (Turcz.) Schischk's roots resulted in the isolation of 16 distinct compounds, including two new aliphatics: sadiesteroside A (1) and 2,3,4-trihydroxyundecanoic acid (2), one new aliphatic hydrocarbon methyl propionate-3-(2-hydroxy-propionate) (3), and thirteen known aliphatics (4-16). The structural elucidation of compounds 1-16 was established by 1D and 2D NMR spectroscopy, supported by high-resolution mass spectrometric analysis and literature references. All isolated compounds' in vitro antiproliferative potential was evaluated using HepG2 cells. The results indicated that compound 3, compound 15, and compound 16 significantly inhibited the activity of HepG2 cells.

Previous studies have demonstrated that the triglyceride-glucose (TyG) index in combination with the estimated glucose disposal rate (eGDR) could predict mortality risks in the normal population. Our studies have focused on their additive effects on patients with cardiovascular-kidney metabolic syndrome (CKM) syndrome stages 0–3. Participants were sourced from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The restricted cubic spline (RCS) curves modeled the associations between the TyG index, eGDR, and mortality. Cox proportional regression models, Kaplan–Meier (KM) curve and subgroup analysis were performed to investigate the combined association. Machine learning was used in the development of predictive models. A total of 11,206 participants with CKM syndrome stages 0–3 were involved. The median follow-up time was 104 days, in which 1,079 cases of all-cause death and 299 cases of cardiovascular death were recorded. The RCS curve proved that the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. Compared with the low TyG/high eGDR group, the all-cause mortality rate in TyG ≥ 8.72 and eGDR < 10.8 group was 14.9

BackgroundThe prognostic value of triglyceride-glucose (TyG) has been well described in patients with coronary artery disease (CAD). Hyperhomocysteinemia (HHcy) promotes insulin resistance and has also been regarded as a potential risk factor for cardiovascular disease. However, the prognostic value of TyG in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and the interaction between TyG and HHcy remain unclear.MethodsA total of 1,734 ACS patients undergoing PCI were continuously enrolled between June 2016 and November 2017 at Beijing Anzhen Hospital. Patients were categorized into four groups based on HHcy status and the optimal cut-off value of TyG. The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization.ResultsOver a median follow-up of 927 days, 358 patients (20.6%) experienced MACE. The Kaplan-Meier curves showed significant differences in the cumulative incidence of MACE among prespecified groups (p < 0.001). Multivariable Cox regression analysis revealed that higher TyG was significantly associated with an increased risk of MACE in patients without HHcy (HR: 2.36, 95% CI: 1.53–3.64, p < 0.001), but not in patients with HHcy (HR: 1.31, 95% CI: 0.60–2.87, p = 0.503). Restricted cubic splines only demonstrated the prognostic value of TyG in patients without HHcy. A significant interaction was observed for MACE between TyG and HHcy (p for interaction = 0.01).ConclusionsThe prognostic value of TyG was modified by HHcy in ACS patients undergoing PCI. Higher TyG was only associated with an increased risk of MACE in ACS patients without HHcy, but not in ACS patients with HHcy.

Echocardiography showed the myocardial ischemia presentation of an 8-month-old boy.

Aging is a critical biological process, with particularly notable impacts on the kidneys. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of transferring various bioactive molecules, which exhibit beneficial therapeutic effects on kidney diseases. This study demonstrates that exosomes derived from hUC-MSCs ameliorate cellular senescence in the kidneys of naturally aging mice. These exosomes reduce the protein expression of senescence markers and senescence-associated secretory phenotypes (SASP) leading to fewer DNA damage foci and increased expression of the proliferation indicator Ki67. During the aging process, many proteins undergo phosphorylation modifications. We utilized data-independent acquisition (DIA) phosphoproteomics to study kidneys of naturally aging mice and those treated with hUC-MSC-derived exosomes. We observed elevated phosphorylation levels of the differentially phosphorylated proteins, Lamin A/C, at Ser390 and Ser392 sites, which were subsequently verified by western blotting. Overall, this study provides a new molecular characterization of hUC-MSC-derived exosomes in mitigating cellular senescence in the kidneys. SIGNIFICANCE: DIA phosphoproteomics was employed to investigate phosphorylated proteins in the kidney tissues of naturally aging mice with hUCMSC-exos treated. The results demonstrated that the DIA technique detected a higher abundance of phosphorylated proteins. We identified 24 significantly differentially phosphorylated proteins, and found that the phosphorylation of specific Lamin A/C sites is crucial for preventing cellular senescence. This study will help to better reveal the related phosphorylated proteins involved in hUCMSC-exos intervention in the kidneys of naturally aging mice, providing a foundation for future research on specific phosphorylation sites of proteins as potential therapeutic targets for renal aging-related diseases.

Nine polyacetylenes, including five new compounds named sadivaethynes E-I (1-5), were isolated from the roots of Saposhnikovia divaricata. Structural elucidation of compounds 1-5 was established by extensive spectroscopic analysis, quantum chemical calculations and DP4+ probability analysis. Among them, the absolute configuration of compound 1-2, 4-5 was unambiguous determined by ECD. Also, all compounds were evaluated for cytotoxicity against two human cancer cell lines (A549, HEPG2) in vitro, compound 9 showed moderate inhibitory effect with an IC50 value of 11.66 mu M against HEPG2.

Background: Because of the limitations in new-generation drug-eluting stents (DES), treatments advocating for non-stents with a drug-coated balloon (DCB) is now of great interest. Here, we conducted a meta-analysis to testify whether a DCB was more effective and safer than a DES in treating de novo coronary artery disease (CAD). Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science to obtain high-quality trials comparing DCB with DES for the treatment of de novo CAD. The primary endpoint was target lesion revascularization (TLR), and the secondary endpoints were in-lesion late lumen loss (LLL), all-cause death, myocardial infarction and binary restenosis. Results: We enrolled 1661 patients from seven randomized clinical trials. Compared with the DES group, the MD (mean difference) of in-lesion LLL was significantly lower in the DCB group (MD -0.19, 95% CI -0.23 to -0.16, p < 0.00001, I2 = 0%). The DCB group showed superiority in small vessel disease (SVD) in in-lesion LLL (MD -0.21, 95% CI -0.34 to -0.08, p = 0.001). Conclusions: The DCB group exhibited a lower in-lesion LLL compared to the DES group, and DCB was not inferior to DES in other endpoints, including in the SVD subgroup. Hence, to our knowledge, DCB is non-inferior to DES for de novo CVD and SVD. DCB in patients with CVD needs further large and long-term clinical trials to demonstrate its long-term efficacy. The PROSPERO Registration: CRD42021268965, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268965.

Objective:To evaluate the subjective olfactory function in chronic sinusitis（CRS）patients with asthma after nasal endoscopic surgery and associated factors that may affect olfactory function. Methods：The study included 90 CRS patients with asthma from January 2008 to December 2020，and all of them underwent endoscopic sinus surgery（ESS）. VAS score of olfactory function before and after surgery were collected，and the data at baseline，3 months，6 months，1 year，3 years，5 years，8 years and 10 years after surgery were compared. Factors affecting olfactory function were analyzed in a generalized mixed linear model，which including age，surgical procedure，allergic rhinitis and so on.Results： The olfactory VAS scores were significantly lower at 3 months，6 months，1 year，3 years，and 5 years postoperatively compared with baseline，and the difference was statistically significant（P<0.05）.Olfactory VAS scores at 8 and 10 years postoperatively were not statistically different from baseline（P>0.05）.Age（≥60 years），aspirin intolerance syndrome，Lund-Kennedy score，modified sinus CT olfactory cleft score，and follow-up time were risk factors, and radical sinus surgery is a protective factor.Conclusion：Subjective olfactory scores in CRS patients with asthma after ESS remain relatively stable for 5 years postoperatively.Prior history of surgery did not affect postoperative subjective olfactory scores. Age，aspirin intolerance syndrome, Lund-Kennedy score，modified sinus CT olfactory cleft score, follow-up time，and surgical approach were strongly associated with subjective olfactory scores in CRS patients with asthma，and radical surgery had a protective effect on olfaction.

Background: Sinonasal inverted papilloma (SNIP) is a benign epithelial tumor with distinctive histopathological features. However, the role of inflammation in SNIP remains poorly characterized. Objectives: This study aimed to compare the histopathological patterns and inflammatory characteristics of SNIP with those of chronic rhinosinusitis with nasal polyps (CRSwNPs) or normal ethmoid sinus mucosa. Methods: Fifty-eight tissue biopsies were prospectively collected from 38 patients with SNIPs, 12 CRSwNPs, and 8 normal ethmoid sinus mucosae. SNIP was histopathologically divided into four grades based on the extent of epithelial remodeling. The immunohistochemical characteristics of epithelial remodeling (p63, CK5) and infiltration of inflammatory cells (eg, eosinophils, neutrophils, and macrophages) and cytokines (eg, interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) were analyzed. Results: Among the 38 SNIPs, 21.1%, 36.8%, 23.7%, and 18.4% were grades I, II, III, and IV, respectively. The expression levels of p63 and CK5 were significantly higher in SNIP than in the other two groups (both, p < 0.05). Neutrophil and macrophage infiltration was more pronounced in SNIP and with differences among the four grades. The expression levels of inflammatory cytokines were significantly higher in the SNIP group than in the CRSwNP group. A positive correlation between the expression levels of p63 and inflammatory cytokines was observed in both SNIPs and CRSwNPs. Conclusion: Excessive epithelial remodeling is an important histological feature of SNIP; it is accompanied by sinonasal mucosal inflammation.