[Research advances on the role of cell senescence in chronic wound healing].

Chronic wounds bring huge pressure and difficulties to patients, their families, and society due to their long-term refractory characteristics and serious poor prognosis. Recently, more and more evidences have proven that cell senescence exists in chronic wounds and affects wound healing. This article reviews the characteristics of cell senescence in chronic wounds, discusses the relationship between cell senescence and chronic wound healing, and summarizes current series of anti-senescence strategies to bring out the possibility of treating chronic wounds with cell senescence as a potential target.

Does the use of tranexamic acid increase the risk of VTE in patients with hemoptysis?

OBJECTIVE: The aim of this study was to create a predictive nomogram that can accurately identify the risk factors of venous thromboembolism (VTE) in hospitalized patients exhibiting hemoptysis. PATIENTS AND METHODS: The present study gathered clinical and demographic data of 1,052 hospitalized patients with hemoptysis at Dongyang Hospital between January 2016 and January 2021 through the Lejiu database. The patients were categorized into two groups: the thrombotic event group (n=123) and the non-thrombotic event group (n=929), based on the presence of VTE before discharge. The study utilized univariable and multivariable logistic regression analyses to identify the independent risk factors for VTE, with the occurrence of thrombotic events serving as the dependent variable. Furthermore, a nomogram prediction model was formulated to verify the findings. RESULTS: In hospitalized patients with hemoptysis, the risk of VTE was found to be independently associated with the administration of tranexamic acid (TXA), the presence of D-dimer, and the Charlson Comorbidity Index (CCI) score (p<0.05). CONCLUSIONS: A nomogram model was constructed to evaluate the probability of VTE in patients hospitalized with hemoptysis. This model allows for the timely detection of early VTE warning signs, which may ultimately reduce its occurrence.

ETV4 promotes the progression of gastric cancer through regulating KDM5D.

OBJECTIVE: This study was aimed to investigate the expression characteristics of ETS variant 4 (ETV4) in gastric cancer (GCa), and to further explore whether it promotes the development of GCa by regulating KDM5D. PATIENTS AND METHODS: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of ETV4 in 35 pairs of tumor tissue and paracancerous tissue specimens collected from GCa patients, and the interplay between ETV4 expression and clinical indexes, as well as the prognosis of GCa patients, were analyzed. Meanwhile, the expression of ETV4 in GCa cell lines was verified using qRT-PCR assay. Furthermore, ETV4 knockdown model was constructed using lentivirus in GCa cell lines including AGS and BGC-823, and then, the transwell invasion and cell wound healing assays were applied to analyze the effect of ETV4 on the biological function of GCa cells. In addition, an in-depth study of the relationship between ETV4 and KDM5D was conducted. RESULTS: The results of qRT-PCR showed that the expression level of ETV4 in GCa tissue samples was remarkably higher than that in adjacent tissues, and the difference was statistically significant. Compared with patients with low expression of ETV4, the patients with high ETV4 expression had a higher occurrence rate of lymph node or distant metastasis and a lower overall survival rate. Similarly, the metastasis ability of GCa cells in the ETV4 expression knockdown group (sh-ETV4) was remarkably decreased when compared with the sh-NC group. In addition, qRT-PCR results indicated that the protein expression of KDM5D was significantly increased after the knockdown of ETV4. Therefore, it was demonstrated that ETV4 might be able to regulate the malignant progression of GCa via modulating KDM5D expression. Finally, the results of the cell reverse experiment confirmed that the silence of ETV4 could reverse the malignant progression of GCa induced by the downregulation of KDM5D. CONCLUSIONS: ETV4 expression was found remarkably elevated in GCa tissues and was significantly associated with the occurrence of lymph node or distant metastasis and poor prognosis. In addition, ETV4 might promote GCa cell metastasis by modulating KDM5D.

[Estimation of Early Postmortem Interval of Asphyxial Death Rats at Different Ambient Temperatures by GC-MS-Based Metabolomics].

ABSTRACT: Objective To establish the orthogonal partial least square （OPLS） model for the estimation of early postmortem interval （PMI） of asphyxial death rats in four ambient temperatures based on gas chromatography-mass spectrometry （GC-MS） metabolomics. Methods The 96 rats were divided into four temperature groups （5 ℃, 15 ℃, 25 ℃ and 35 ℃）. Each temperature group was further divided into 3 h, 6 h, 12 h and 24 h after death, and 6 other rats were taken as the control group. The cardiac blood was collected at the set time points for the four temperature groups and 0 h after death for the control group for the metabolomics analysis by GC-MS. By OPLS analysis, the variable importance in projection （VIP）>1 and the result of Kruskal-Wallis test P<0.001 were used to screen out the differential metabolite related to PMIs in the cardiac blood of rats of different temperature groups. Then OPLS regression models of different temperature groups were established with these metabolites. At the same time, a prediction group for investigating the prediction ability of these models was set up. Results Through the analysis of OPLS, 18, 15, 24 and 30 differential metabolites （including organic acids, amino acids, sugars and lipids） were screened out from the rats in groups of 5 ℃, 15 ℃, 25 ℃ and 35 ℃, respectively. The prediction results of the four temperature group models showed that the prediction deviation of 5 ℃ model was larger than that of other groups. The prediction results of other temperature groups were satisfactory. Conclusion There are some differences in the changes of metabolites in cardiac blood of rats at different ambient temperatures. The influence of ambient temperature should be investigated in the study of PMI estimation by metabolomics, which may improve the accuracy of PMI estimation.

Ineffectiveness of the Tobacco Hazards Prevention Act in patients with severe and persistent mental illness.

OBJECTIVES: The effect of the Tobacco Hazards Prevention Act (THPA) on the reduction of tobacco use in the general population in Taiwan is understood. However, there has been little research on how these policies affect people with severe and persistent mental illness (SPMI). Hence, the influence of the THPA on daily cigarette use by patients with SPMI was investigated in a 3-year follow-up. The risk and protective factors in smoking behavior and cessation were investigated. STUDY DESIGN: This is an observational study. METHODS: A total of 144 participants (78 of whom had smoked >100 cigarettes throughout their lifetime) were randomly selected from a healthcare network. Then, 100 of 144 patients with SPMI, included 50 smokers and 50 non-smokers, have agreed with 1st year follow-up. Eighty-two patients with SPMI, consisted of 44 smokers and 38 non-smokers, have agreed with 2nd year follow-up. RESULTS: Although women were less likely to smoke than men, those who did smoke reduced the number of cigarettes less than men over the 3-year period. Less-educated patients were more likely to smoke than those who were more educated but reduced the number of daily cigarettes more after implementation of the THPA. Maternal overprotection was a risk factor and paternal care a protective factor for smoking. Addiction, a perception of pleasure, interpersonal relationships, and self-destructive behavior increased cigarette smoking. Patients perceived that smoking alleviated their depressive symptoms. CONCLUSIONS: The THPA was ineffective for patients with SPMI. Some factors had different effects on the development of smoking behavior and the cessation process. Understanding the etiology of smoking can help policymakers establish more effective programs for smoking prevention and cessation.

The significance of HBD-3 and fluorescent composite carriers in the processof bone formation in rats infected with Staphylococcus aureus.

OBJECTIVE: The objective of the present study was to explore the significance of human ß-defensin 3 (HBD-3) through establishment and evaluation of the model of implant-related biofilm infection of the femoral condyle of the outer knee using Sprague-Dawley (SD) rats. MATERIALS AND METHODS: Age-matched SD rats were divided into three groups, the HBD-3 group, HBD-3 fluorescent liposome group, and the HBD-3 liposome-microbubble fluorescent composite carrier group. After biofilm infection for 24 h, the fluorescent composite vector was injected intraperitoneally 2 times/day. After the first injection, rats in each group were sacrificed on the 7th, 14th, and 28th day. The lower end of the femur bone was harvested after removing the surrounding soft tissue. H&E and immunohistochemical staining were applied and light microscopy was used for observation. Fluorescent markers including tetracycline and calcein were used to follow the formation of new bone in vivo. Undecalcified specimens were embedded in epoxy resin (thickness of roughly 150 m), and confocal microscopy was used for observation. RESULTS: By assessing cell proliferation with cell counting kit-8, the proliferation ability of cells in the HBD-3 liposome-microbubble fluorescent composite carrier group was significantly increased compared with the other groups (p<0.05). qPCR was used to measure the levels of alkaline phosphatase (ALP), type I collagen, osteocalcin (OCN), osteopontin (OPN), and bone sialoprotein (BSP) in each group. The levels of these genes in the HBD-3 liposome-microbubble fluorescent composite carrier group were significantly higher than those in other groups (p<0.05). CONCLUSIONS: The application of the HBD-3 liposome-microbubble fluorescent composite carrier can significantly promote osteogenesis in rats infected with Staphylococcus aureus, and increase the expression levels of ALP, type I collagen, OCN, OPN, and BSP.

Genetic polymorphisms in the prostaglandin pathway genes and risk of head and neck cancer.

OBJECTIVE: Previous studies examining the association between genetic variations in prostaglandin pathway and risk of head and neck cancer (HNC) have only included polymorphisms in the PTGS2 (COX2) gene. This study investigated the association between genetic polymorphisms of six prostaglandin pathway genes (PGDS, PTGDS, PTGES, PTGIS, PTGS1 and PTGS2), and risk of HNC. METHODS: Interviews regarding the consumption of alcohol, betel quid, and cigarette were conducted with 222 HNC cases and 214 controls. Genotyping was performed for 48 tag and functional single-nucleotide polymorphisms (SNPs). RESULTS: Two tag SNPs of PTGIS showed a significant association with HNC risk [rs522962: log-additive odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.01-1.99 and dominant OR = 1.58, 95% CI: 1.02-2.47; rs6125671: log-additive OR = 1.49, 95% CI: 1.08-2.05 and dominant OR = 1.96, 95% CI: 1.16-3.32]. In addition, a region in PTGIS tagged by rs927068 and rs6019902 was significantly associated with risk of HNC (global P = 0.007). Finally, several SNPs interacted with betel quid and cigarette to influence the risk of HNC. CONCLUSIONS: Genetic variations in prostaglandin pathway genes are associated with risk of HNC and may modify the relationship between use of betel quid or cigarette and development of HNC.

A survey on the management of acute rhinosinusitis among Asian physicians.

BACKGROUND: Based on the `European Position Paper on Rhinosinusitis and Nasal polyps (EP3OS 2007)`, this study aimed to investigate general practitioners (GPs) and other specialists` understanding when managing patients with acute rhinosinusitis (ARS) in Asia. METHODOLOGY: Among a total of 2662 questionnaires completed, 2524 (94.8%) were valid for analysis. There were 1308 GPs (51.8%), 989 otolaryngologists (39.2%) and 227 paediatricians (9%) from Mainland China, Hong Kong, Indonesia, India, Malaysia, Pakistan, Philippines, Singapore, Thailand and Taiwan. RESULTS: ARS is affecting an estimated 6 - 10% of patients seen in a daily out-patient practice. The EP3OS criteria are well supported by Asian physicians (94.1%). Most physicians (62.7%) agreed that radiological investigation is not needed to diagnose ARS. However, even for mild ARS (common cold), medical treatments were still recommended by 87% of GPs, 83.9% of otolaryngologists, and 70% of paediatricians. The top three first-line treatments prescribed were antihistamines (39.2%), nasal decongestants (33.6%), and antibiotics (29.5%). Antibiotics usage increased as the first line treatment of moderate (45.9%) and severe (60.3%) ARS. CONCLUSION: ARS is commonly managed by GPs, otolaryngologists, and paediatricians in Asia. However, understanding of the management of ARS needs further improvement to minimize unnecessary use of radiological investigations, overuse of antibiotics, and under use of nasal corticosteroids.

Neural activities associated with emotion recognition observed in men and women.

Previous studies have suggested that men and women process emotional stimuli differently. In this study, we examined if there would be any consistency in regions of activation in men and women when processing stimuli portraying happy or sad emotions presented in the form of facial expressions, scenes, and words. A blocked design BOLD functional magnetic resonance imaging paradigm was employed to monitor the neural activities of male and female healthy volunteers while they were presented with the experimental stimuli. The imaging data revealed that the right insula and left thalamus were consistently activated for men, but not women, during emotion recognition of all forms of stimuli studied. To further understand the imaging data acquired, we conducted the protocol analysis method to identify the cognitive processes engaged while the men and women were viewing the emotional stimuli and deciding whether they were happy or sad. The findings suggest that men rely on the recall of past emotional experiences to evaluate current emotional experiences. This may explain why the insula, a structure important for self-induced or internally generated recalled emotions, was consistently activated in men while processing emotional stimuli. Our findings suggest possible gender-related neural responses to emotional stimuli.

Branchiogenic squamous cell carcinoma: a case report.

Branchiogenic carcinoma is extremely rare. A 41-year-old man presented with a well-defined, fluctuant, painless mass on his right neck and received complete tumour excision. The pathological diagnosis was branchial cleft squamous cell carcinoma, which was characterized microscopically by a branchial cleft cyst with a tumour and a non-tumour transitional zone. In the past, several hundred cases were reported erroneously because of the rather complicated diagnostic criteria. The modified criteria of Khafif introduced in 1989 are more practical, and all were met in this case.

Overexpression of Fas-ligand in human nasal polyps.

Apoptosis mediated through the Fas/Fas-L system is essential in regulating immune function, developing organs, and conferring immune privilege. To illustrate the role of the Fas/Fas-L system in the pathogenesis of human nasal polyps, we investigated the transcripts and protein level of the Fas-L gene in 8 human nasal polyp tissues and 7 nasal turbinate mucosa specimens using reverse transcription-polymerase chain reaction and Western blotting. Localization of Fas-L was performed with immunohistochemistry. The transcripts of the Fas-L gene were detected at similar levels in both polyps and nasal mucosa. There was a significant overexpression of Fas-L protein on nasal polyps compared to nasal mucosa. Fas-L-positive cells were localized on the epithelial layers of cystically dilated glands and the down-growing epithelium of nasal polyps. Fas-L may play an important role in the pathogenesis of human nasal polyps, including cystic degeneration of submucosal glands and conferring of immune privilege to nasal polyp formation.

Hypertonic saline nasal provocation stimulates nociceptive nerves, substance P release, and glandular mucous exocytosis in normal humans.

Hypertonic saline (HTS) induces bronchoconstriction. Potential mechanisms were evaluated in a human nasal provocation model. Aliquots of normal saline (1 x NS, 100 microliters) and higher concentrations (3 x NS, 6 x NS, 12 x NS, 24 x NS) were sprayed into one nostril at 5-min intervals. Lavage fluids were collected from the ipsilateral and contralateral sides to determine the concentrations of specific mucus constituents. Nasal cavity air-space volume was assessed by acoustic rhinometry (AcRh). The distribution of substance-P-preferring neurokinin-1 (NK-1) receptor mRNA was assessed by in situ reverse transcriptase-polymerase chain reaction. Unilateral HTS induced unilateral dose-dependent increases in sensations of pain, blockage, and rhinorrhea, the weights of recovered lavage fluids, and concentrations of total protein, lactoferrin, mucoglycoprotein markers, and substance P. Contralateral, reflex-mediated effects were minor. There were no changes in IgG or AcRh measurements. NK-1 receptor mRNA was localized to submucosal glands. HTS caused pain with unilateral substance P release. The presumed nociceptive nerve efferent axon response led to glandular exocytosis, presumably through actions on submucosal gland NK-1 receptors. Vascular processes, including plasma exudation, filling of venous sinusoids, and mucosal edema were not induced in these normal subjects.

Analysis of the expression of Fas-L in nasopharyngeal carcinoma tissues.

Nasopharyngeal carcinoma (NPC) is an epithelial cancer with a high incidence in Southeast Asia. How it escapes attack from the host immune system is not fully understood. Recently, pieces of evidence show that Fas-ligand (Fas-L)-mediated apoptosis may be involved in immune privilege of tumours. To determine whether a similar mechanism may exist in NPC, the expression of Fas-L was analysed. Biopsy specimens of the nasopharynx were taken from 27 NPC patients. Histologically, they were either non-keratinizing or undifferentiated carcinomas. Nasopharyngeal biopsies of 11 other patients that proved to have no tumour served as control. The transcripts of Fas-L were detected by reverse transcription-polymerase chain reaction. Localization of Fas-L protein was performed with immunohistostaining using an antibody recognizing human Fas-L. All nasopharyngeal tissues have a similar amount of transcripts of Fas-L. However, the Fas-L protein was detected exclusively on the cell surface of malignant epithelial cells of NPC. The present findings suggest that Fas-L protein may be involved in evading immune attack of NPC.

Application of endoscopic sinus surgery to primary atrophic rhinitis? A clinical trial.

The aetiology of primary atrophic rhinitis (AR) is still unclear. Based on the sinus infection theories, endoscopic sinus surgery (ESS) was applied to treat AR. ESS was performed on 14 patients following Stammberger's techniques along with middle turbinectomy. Patients were evaluated using clinical symptoms, radiological sinus images, saccharine time tests, bacterial cultures and mucosal ultrastructures, before and 2 years after ESS. Three patients had good recoveries, 6 had partial recoveries and another 5 had persistent disease. Good recovery patients showed clear nasal cavities and mucociliary transport system normalisation. Patients possess in meagre infectious signs or crusting extending to their nasopharynx had poor outcomes. Patients with evidence of obvious infections (cloudy sinus images, mucopus presence in the sinuses and positive culture for Klebsiella ozaenae) had good recoveries following ESS. Candidate selection is critical for the success of ESS treatment in AR. Although further clinical trials are required to prove this strategy.

Distribution and quantity of neuroendocrine markers in allergic rhinitis.

Neuroendocrine components exist in the human nasal mucosa. However, the pathophysiological and neuroimmunological roles of the regulatory peptides in allergic rhinitis (AR) require further investigation. To analyse the functional morphology and quantify the tissue concentration of regulatory peptides in the nasal mucosa of AR subjects, human inferior turbinate mucosa specimens from 25 patients with AR, 20 patients with non-allergic rhinitis and 10 patients without any nasal diseases were investigated. Using immunohistochemistry and radioimmunoassays, we detected the presence, distribution and concentrations of various neuropeptides [vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP) and calcitonin gene-related peptide (CGRP)] and general neuroendocrine markers (neuron-specific enolase and chromogranin A). Quantitative analysis of the stained fibres and cells was performed using a graphic AutoCAD program. The presence and distribution of NPY, CGRP and SP nerve fibres and neuroendocrine cells were similar among the three subject groups. AR subjects had significantly higher tissue concentrations of VIP and SP. AR subjects had increased numbers of VIP fibres which predominantly innervated vessels. Thus, VIP and SP play important neuroimmunological roles in the pathogenesis of AR.

Immunohistochemistry of p53 in sinonasal inverted papilloma and associated squamous cell carcinoma.

Gene mutation of p53 is documented in head and neck cancer. No reports exist relating human sinonasal inverted papilloma (IP) and its transformation to squamous cell carcinoma (SCC). Using immunohistochemical techniques improved by an antigen retrieval method, p53 protein was analyzed in the following subjects: 16 IP, 12 SCC arising in IP, and 15 SCC alone subjects. Both the intensity (PI) and rate (PR) of positive p53 immunostaining were evaluated using a quantitative AutoCAD program. We correlated p53 protein expression with clinical features. p53 immunoreactivity is significantly lower in IP than in SCC specimens. Both the IP and SCC portions of IP synchronous SCC subjects showed similar p53 protein expression. SCC arising in IP shows a lower p53 immunoreactivity than SCC alone. Alteration of p53 protein may have an important role in the early stages of IP malignant transformation and prove a potential biomarker for risk assessment. Low p53 immunoreactivity, indicating the presence of a wild-type p53, may correlate with the prognosis for SCC arising in IP. However, further clinical trials are required to investigate this possibly worthwhile prognostic marker.

Anticholinergic properties of brompheniramine, chlorpheniramine, and atropine in human nasal mucosa in vitro.

Brompheniramine and chlorpheniramine have anticholinergic activities, but the relative potency of these effects has not been well defined. The anticholinergic properties of brompheniramine, chlorpheniramine, and atropine were assessed in an in vitro model of human nasal mucosal glandular secretion. Methacholine was used as a cholinergic agonist to stimulate glandular secretion of 7F10-mucin. These drugs (0.01-1000 microM) or vehicle (saline) were added to explant cultures with and without 100 microM methacholine. 7F10-mucin concentrations were measured in culture supernatants after 2-hour incubations. The effective dose reducing methacholine-induced secretion (ED50) was determined. ED50 was 0.25 microM for atropine, 4.10 microM for brompheniramine, and 4.63 microM for chlorpheniramine. None of the anticholinergic drugs changed spontaneous glandular exocytosis. Brompheniramine and chlorpheniramine are equipotent anticholinergic agents in human nasal mucosa in vitro. Atropine was 16 to 19 times more potent.

Assessment of p53 protein expression in normal mucosa and benign and malignant lesions of the nasal cavity.

p53 gene mutation is documented in head and neck cancer. No reports exist relating this mutation to normal mucosa or benign and malignant lesions of the nasal cavity. We investigate p53 overexpression using immunohistochemical techniques improved by an antigen retrieval method. p53 protein was analyzed in the following cases: normal, benign [papilloma and inverted papilloma (IP)] and malignant [squamous-cell carcinoma (SCC) arising in IP, SCC alone, adenocarcinoma and small-cell carcinoma]. Both the intensity and rate of positive p53 immunostaining were evaluated using a quantitative Auto-CAD program. Overexpression of p53 protein was not identified in normal mucosa, benign or premalignant lesions; however, approximately 60% is correlated to nasal cancer. p53 overexpression correlates with heavy smoking. Both the IP and SCC portions of SCC synchronous with IP showed similar p53 immunoreactivity. SCC arising in IP shows a lower p53 immunoreactivity than SCC alone. Thus, smoking along with a p53 mutation may be a mutagenic agent in nasal cancers. Alteration of the p53 protein may play an important role in the early stages of the malignant transformation of IP. A low p53 immunoreactivity indicates the presence of wild-type p53 protein. This may show a better response to radiation therapy yielding a better prognosis for SCC arising in IP compared to SCC alone. However, further clinical trials are required to investigate this possibly worthwhile prognostic marker.

Neuropeptide innervation and neuroendocrine cells in allergic rhinitis and chronic hypertrophic rhinitis.

BACKGROUND: The neuropeptides and neuroendocrine cells are proven to exist in the human nasal mucosa. However, the pathophysiological and neuroimmunological roles of regulatory peptides in human nasal diseases require further investigation. OBJECTIVES: To investigate and compare the functional morphology and quantify the tissue concentration of regulatory peptides in the nasal mucosas of normal, allergic rhinitis (AR) and chronic hypertrophic rhinitis (CHR) subjects. METHODS: Human inferior turbinate mucosa specimens from 28 patients with AR, 25 patients with CHR and 15 patients without any nasal diseases were investigated. Using immunohistochemistry and radioimmunoassays, we detected the presence, distribution and concentrations of various neuropeptides (vasoactive intestinal peptides [VIP], neuropeptide Y [NPY], substance P [SP], calcitonin gene-related peptides [CGRP]) and general neuroendocrine markers (neurone-specific enolase, chromogranin A and somatostatin). Quantitative analysis of the stained fibres and cells were performed using a graphic AutoCAD program. RESULTS: The presence and distribution of NPY, CGRP, and SP nerve fibres and neuroendocrine cells were similar among the three subject groups. AR subjects had significantly higher VIP and SP tissue concentrations. VIP fibres had highest density in AR subjects and these fibers predominantly innervated vessels. In CHR, VIP fibres primarily innervated glands. CONCLUSIONS: VIP and SP may play an important neuroimmunological role in the pathogenesis of AR. VIP may lead to the hypertrophic changes of submucosal glands in the pathogenesis of CHR.

Lectin immunohistochemistry study of nasal inverted papilloma and associated neoplasms.

BACKGROUND: We aimed to investigate the tumor biology of nasal IP and identify the biological characteristics associated with early diagnosis and malignant transformation. MATERIALS AND METHODS: Lectins immunohistochemistry were performed on inverted papilloma (IP), and associated neoplasms. IP synchronized with polyp or squamous cell carcinoma (SCC) and IP metachronized with SCC were analyzed and correlated to clinical information. RESULTS: Canavalia ensiformis (ConA) and Arachis hypogaea (PNA) with neuraminidase pretreatment (NA-PNA) showed similar staining in both the IP and SCC portions of the IP synchronized with SCC. The IP and polyp portions of an IP synchronized polyp had positive NA-PNA staining, while papilloma and polyps alone had negative staining. Strong NA-PNA staining in the IP (transformed to SCC) showed significant differences from IP. CONCLUSION: These biological characteristics define IP as a premalignant neoplasm. NA-PNA staining may be helpful for an early detection of IP. Strong NA-PNA staining in IP may predict malignant transformation.