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Astragalus polysaccharides (APSs), the compounds extracted from the common herb Astragalus membranaceus, have been extensively studied for their antitumor properties. In this study, we investigated the effect of APS on lung adenocarcinoma A549 cells. The effects of APS and the anti-diabetic drug metformin on apoptosis and ferroptosis were compared. Furthermore, the combination treatment of APS and metformin was also investigated. We found that APS not only reduced the growth of lung cancer cells but also had a synergistic effect with metformin on A549 cells. The study results showed that it may be promising to use APS and metformin as a combination therapy for the treatment of lung adenocarcinoma.

Abstract We probed the associations of preoperative modified geriatric nutritional risk index (mGNRI) values with prognosis in patients receiving surgery for oral cavity squamous cell carcinoma (OCSCC). This retrospective study analyzed the clinical data of 333 patients with OCSCC and undergoing surgery between 2008 and 2017. The preoperative mGNRI was calculated using the following formula: (14.89/C-reactive protein level) + 41.7 × (actual body weight/ideal body weight). We executed receiver operating characteristic curve analyses to derive the optimal mGNRI cutoff and employed Kaplan–Meier survival curves and Cox proportional hazard model to probe the associations of the mGNRI with overall survival (OS) and disease-free survival (DFS). The optimal mGNRI cutoff was derived to be 73.3. We noted the 5-year OS and DFS rates to be significantly higher in the high-mGNRI group than in the low-mGNRI group (both p

[This corrects the article DOI: 10.1371/journal.pone.0251455.].

Abstract Background To date, treating nasal polyps (NPs) is still a medical challenge. However, we have developed an innovative therapy using licorice extract (LE: Glycyrrhiza glabra) to treat rhinitis and sinusitis via nasal irrigation and have discovered that it significantly affects treatment of NPs. Hypothesis/purpose This study investigated the mechanism of LE on NPs. Study design NPs were collected from three patients using tissue biopsies before and 2 weeks after nasal irrigation with licorice for histopathological analysis. Additionally, NPs from two patients were collected, and nasal polyp-derived fibroblasts (NPDF) were isolated and cultured. Methods The TGF-β1-stimulated NPDF model was used to examine the effect of LE on fibroblast differentiation (biomarker: α-SMA), the consequent production of extracellular matrix (ECM; biomarkers: fibronectin, FBN), and the functional signaling pathway. Results Immunohistochemistry (IHC) revealed that the number of eosinophils and the expression of α-SMA and interstitial collagen of polyps after licorice treatment significantly decreased. Additionally, RT-PCR, western blotting, and immunofluorescence (IF) showed that α-SMA and FBN expressions were significantly increased in the NPDF, which was stimulated by TGF-β1, and LE dose-dependently could effectively reduce this effect. Furthermore, western blotting showed that LE could attenuate α-SMA and FBN expressions by preventing the signaling pathway of MAPK/ERK-1/2, which IHC and IF further confirmed. In addition, LE effectively suppressed the cell migration of NPDF, which is related to polyp expansion. Conclusion LE is clinically used to treat sinusitis with NPs through nasal irrigation, which significantly reduces the size of NPs. This effect could attenuate fibroblast differentiation, ECM production and cell migration, and one of the functional mechanisms may be through inhibition of the MAPK/ERK-1/2 signaling pathway. Trial registration ISRCTN (No. 51425529) registered on 17/04/2020 (retrospectively registered) - http://www.isrctn.com/ISRCTN51425529

The Chiehyuan herbal oral protection solution (GB-2) is a herbal mixture commonly utilized in Taiwan for combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per traditional Chinese medicine practices. This study assessed the clinical impact of GB-2 through prospective clinical trials. With twice-daily use for a week, GB-2 was shown to diminish the expression of angiotensin-converting enzyme 2 (ACE2) in oral mucosal cells. Moreover, after two weeks of use, it could reduce transmembrane protease, serine 2 (TMRPSS2) expression in these cells. Additionally, in vitro experiments demonstrated that GB-2 lessened the entry efficiency of the Omicron, L452R–D614G, T478K–D614G, and L452R–T478K–D614G variants of the SARS-CoV-2 pseudotyped lentivirus. It also impeded the interaction between ACE2 and the receptor-binding domain (RBD) presenting N501Y–K417N–E484A–G339D–Q493R–G496S–Q498R and L452R–T478K mutations. Glycyrrhizic acid, a major compound in GB-2, also hindered the entry of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus by obstructing the binding between ACE2 and the RBD presenting the N501Y–K417N–E484A–G339D–Q493R–G496S–Q498R mutation. To sum up, these findings suggest that GB-2 can decrease ACE2 and TMPRSS2 expression in oral mucosal cells. Both glycyrrhizic acid and GB-2 were found to reduce the entry efficiency of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus and block the binding between ACE2 and the RBD with the N501Y–K417N–E484A–G339D–Q493R–G496S–Q498R mutation. This evidence implies that GB-2 might be a potential candidate for further study as a preventative measure against SARS-CoV-2 infection.

Abstract Background Chronic rhinosinusitis (CRS) affects the quality of life of many people worldwide and can cause comorbidities. Our previous research proved that Sjogren’s syndrome (SS) is a predisposing factor for CRS, with a 2.5-fold associated risk. Antibiotics are important in CRS treatment; however, there is a paucity of research on the pathogenic bacteria of SS-CRS in the past. We conducted this study to investigate the pathogenic difference of SS-CRS and non-SS-CRS and aimed to give clinicians references when selecting antibiotics to treat SS-CRS. Materials and methods A total of 14,678 patients hospitalized for CRS operation from 2004 to 2018 were identified from the Chang Gung Research Database. These CRS cases were classified as either SS-CRS or non-SS-CRS. We analyzed their bacterial distribution by studying the results of the pus cultures performed alongside surgery. Results The top three facultative anaerobic or aerobic isolated bacteria in the SS-CRS group were coagulase-negative Staphylococcus (CoNS: 34.3%), Pseudomonas aeruginosa (28.6%), methicillin-sensitive Staphylococcus aureus (MSSA: 20%), and Staphylococcus epidermidis (20%). In the non-SS-CRS group, S. epidermidis (29.3%), CoNS (25.7%), and MSSA (14.2%) were identified. The top three anaerobic bacterial genera were Cutibacterium (54.3%), Peptostreptococcus (11.4%), and Fusobacterium (11.4%) in the SS-CRS group and Cutibacterium (53.8%), Peptostreptococcus (25%), and Prevotella (12.9%) in the non-SS-CRS group. Conclusions P. aeruginosa is a major pathogen in SS-CRS patients. In addition, physicians should be aware of potential Fusobacterium and antibiotic-resistant bacterial infection in patients with SS-CRS.

We investigated the prognostic utility of preoperative neck lymph node-to-primary tumor maximum standardized uptake value ratios (NTRs) in oral cavity squamous cell carcinoma (OSCC). We retrospectively reviewed the medical records of 141 consecutive patients who were diagnosed as having OSCC and had received fluorodeoxyglucose–positron emission tomography within 2 weeks prior to radical surgery between 2009 and 2018. To determine the optimal NTR cutoff, receiver operating characteristic analysis for overall survival (OS) was executed. The NTR’s prognostic value for disease-free survival (DFS) and OS were determined through Cox proportional hazards analysis and the Kaplan–Meier method. We determined the median (range) follow-up duration to be 35.2 (2.1–122.4) months. The optimal NTR cutoff was 0.273, and patients with a higher NTR (≥0.273) exhibited significantly worse DFS and OS (p = 0.010 and 0.003, respectively). A higher NTR (≥0.273) predicted poorer DFS (hazard ratio: 2.696, p = 0.008) and OS (hazard ratio: 4.865, p = 0.003) in multivariable analysis. We created a nomogram on the basis of the NTR, and it could accurately predict OS (concordance index: 0.774). Preoperative NTRs may be a useful prognostic biomarker for DFS and OS in patients with OSCC who have undergone surgery. NTR-based nomograms may also be helpful prognostic tools in clinical trials.

Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson’s disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.

Objectives Type 2 diabetes mellitus (T2DM) is a risk factor for deep neck infection (DNI) and leads to complications and poor outcomes. Our study aimed to investigate the risk, prognosis, and complications of peritonsillar abscess (PTA) in patients with T2DM. Methods We extracted data of patients newly diagnosed as having T2DM between January 2000 and December 2011 from Taiwan’s National Health Insurance Research Database. These patients were matched with patients without T2DM, and PTA incidence was compared between both cohorts. Results In total, 67,852 patients with and 135,704 patients without T2DM were enrolled. PTA incidence was significantly higher in patients with T2DM (incidence rate ratio, 1.91; P5 years after T2DM diagnosis. Cox regression analysis showed that patients with T2DM had an approximately 2-fold higher PTA risk (adjusted hazard ratio [aHR]: 1.89, P

BackgroundStudies have reported inconsistent results regarding the prognostic value of the systemic immune–inflammation index (SII) in head and neck cancer (HNC). Thus, the present meta-analysis assessed the literature on the prognostic value of SII in those with HNC.MethodsThe Cochrane Library, EMBASE, and PubMed databases were searched, and study methodological quality was assessed using the Newcastle–Ottawa quality assessment scale. To determine the association of the SII with survival outcomes, pooled hazard ratios (HRs) as well as the associated 95% confidence intervals (CIs) were used. To assess the associations of the SII with clinicopathological features, the odds ratios (ORs) and corresponding 95% CIs were considered. Begg’s funnel plot and Egger’s linear regression test were used to assess publication bias.ResultsA total of 12 studies that together enrolled 4369 patients with HNC were analyzed. In the pooled results, a high pretreatment SII was correlated with poorer overall survival (HR = 2.09, 95% CI = 1.62–2.70, p < 0.001), disease-free survival (HR = 2.79, 95% CI = 1.99−3.89, p < 0.001), and progression-free survival (HR = 1.80, 95% CI = 1.30−2.48, p < 0.001). A stratified analysis indicated that SII for overall survival was applicable regardless of tumor site, treatment modality, overall stage, sample size, SII cutoff, and method for determining the SII cutoff. Furthermore, a high SII was correlated with a more advanced T classification (OR = 1.14, 95% CI = 1.09–1.18, p < 0.001) and nodal metastasis (OR = 1.55, 95% CI = 1.18–2.05, p = 0.002) in patients with HNC.ConclusionsAn elevated pretreatment SII predicts more advanced tumor and nodal status and poorer survival outcomes in cases of HNC. Because the measurement of SII is convenient and its use is cost-effective, we suggest that it can be applied by clinicians in the management of HNC.

(1) Background: Physiological changes in nasal patency in response to posture contribute to sleep-related problems. Previously, we reported that the supine and prone positions cause a significant decrease in nasal patency in subjective and objective assessments of healthy individuals. Therefore, we conducted a study to evaluate the effect of posture on nasal patency in patients with allergic rhinitis (AR); (2) Methods: The present study comprised 30 patients diagnosed with AR and 30 healthy subjects without nasal disease (non-AR). Changes in nasal patency were evaluated in the sitting, supine, and prone positions. We used the visual analog scale to evaluate subjective nasal blockage. Acoustic rhinometry and endoscopy were used to objectively measure changes in nasal patency; (3) Results: In the non-AR group, the prone position had a significant effect on subjective nasal blockage compared with the sitting position, with significant decreases in the minimal cross-sectional area (mCSA) measured by acoustic rhinometry. Furthermore, endoscopy demonstrated a significantly increased inferior turbinate hypertrophy in the non-AR group. In the AR group, there was no statistical difference in subjective nasal blockage symptoms between the different positions. However, in objective examinations (acoustic rhinometry and endoscopy), the prone position showed significantly decreased nasal patency; (4) Conclusions: In patients with AR, subjective nasal blockage did not significantly increase in the supine or prone position. Endoscopy demonstrated increased inferior turbinate hypertrophy in supine and prone positions resulting in a significant reduction in nasal cavity mCSA, indicating an objective reduction in nasal patency.

Acute epiglottitis (AE) is a potential emergency of the respiratory tract caused mainly by bacterial infection. However, nonbacterial infection causes, such as corrosive injuries, may result in death due to gastrointestinal perforation if a timely diagnosis is not available. We report the case of an elderly patient with an acute melancholic episode who encountered corrosive epiglottitis (CE) caused by accidental ingestion of hydrochloric acid and compare the features of CE and AE, including the immediate onset of symptoms, normal findings on blood tests, and endoscopy revealing pale swollen epiglottitis. This case can prove to be an important reference for clinicians for differential diagnosis, especially when treating epiglottitis in patients with psychiatric disorders and unclear expression.

Abstract Patients with end-stage renal disease (ESRD) may demonstrate secondary hyperparathyroidism (SHPT), characterized by parathyroid hormone oversecretion in response to electrolyte imbalance (e.g., hypocalcemia and hyperphosphatemia). Moreover, this electrolyte imbalance may affect vocal cord muscle contraction and lead to voice change. Here, we explored the effects of SHPT on the voices of patients with ESRD. We used data of 147,026 patients with ESRD from the registry for catastrophic illness patients, a sub-database of Taiwan National Health Insurance Research Database. We divided these patients into 2 groups based on whether they had hyperparathyroidism (HPT) and compared vocal dysfunction (VD) incidence among them. We also prospectively included 60 ESRD patients with SHPT; 45 of them underwent parathyroidectomy. Preoperatively and postoperatively, voice analysis was used to investigate changes in vocal parameters. In the real-world database analysis, the presence of HPT significantly increased VD incidence in patients with ESRD (p = 0.003): Cox regression analysis results indicated that patients with ESRD had an approximately 1.6-fold increased VD risk (p = 0.003). In the clinical analysis, the “jitter” and “shimmer” factors improved significantly after operation, whereas the aerodynamic factors remained unchanged. In conclusion, SHPT was an independent risk factor for VD in patients with ESRD, mainly affecting their acoustic factors.

At the time of writing, more than 440 million confirmed coronavirus disease 2019 (COVID-19) cases and more than 5.97 million COVID-19 deaths worldwide have been reported by the World Health Organization since the start of the outbreak of the pandemic in Wuhan, China. During the COVID-19 pandemic, many variants of SARS-CoV-2 have arisen because of high mutation rates. N501Y, E484K, K417N, K417T, L452R and T478K in the receptor binding domain (RBD) region may increase the infectivity in several variants of SARS-CoV-2. In this study, we discovered that GB-1, developed from Chiehyuan herbal formula which obtained from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and RBD with Wuhan type, K417N-E484K-N501Y and L452R-T478K mutation. In addition, GB-1 inhibited the binding between ACE2 and RBD with a single mutation (E484K or N501Y), except the K417N mutation. In the compositions of GB-1, glycyrrhizic acid can inhibit the binding between ACE2 and RBD with Wuhan type, except K417N-E484K-N501Y mutation. Our results suggest that GB-1 could be a potential candidate for the prophylaxis of different variants of SARS-CoV-2 infection because of its inhibition of binding between ACE2 and RBD with different mutations (L452R-T478K, K417N-E484K-N501Y, N501Y or E484K).

Abstract Background This study evaluated the treatment outcomes of the primary surgery (PS) or concurrent chemoradiotherapy (CCRT) as the initial treatment for hypopharyngeal squamous cell carcinoma (HPSCC). Methods This retrospective cohort study included patients with stages III–IV HPSCC from four tertiary referral centers consecutively enrolled from 2003 to 2012; of them, 213 (32.6%) and 439 (67.4%) had received PS and CCRT as their primary treatments, respectively. The 5-year overall survival (OS) and disease-free survival (DFS) rates were analyzed using the Kaplan–Meier method and Cox regression models. Results In patients undergoing PS and CCRT, OS rates were 45.0% and 33.1% (p < 0.001), respectively, and DFS rates were 36.2% and 28.9% (p = 0.003), respectively. In subgroup analysis, in patients with stage IVA HPSCC, PS was associated with higher OS rate (p = 0.002), particularly in those with T4 or N2 classification (p = 0.021 and 0.002, respectively). Multivariate analysis indicated that stage IVA HPSCC, stage IVB HPSCC, and CCRT were independent adverse prognostic factors for OS rate (p = 0.004, < 0.001, and 0.014, respectively). Furthermore, in patients with stage IVA HPSCC aged ≥ 65 years and with N2 classification, CCRT was significantly associated with lower OS rates than was PS (p = 0.027 and 0.010, respectively). Conclusions In patients with advanced HPSCC, PS was significantly associated with better prognosis than CCRT. PS could be a favorable primary treatment modality for the management of patients with stage IVA HPSCC, particularly those aged ≥ 65 years and with T4 and N2 classification.

AimWe probed the prognostic value of the preoperative high-sensitivity modified Glasgow prognostic score (HS-mGPS), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) for patients with oral cavity squamous cell carcinoma (OSCC) to identify patients with the highest risk of having poor survival outcomes.Materials and MethodsWe executed a retrospective assessment of the records of 303 patients with OSCC who had been subjected to curative surgery between January 2008 and December 2017. The HS-mGPS was categorized using C-reactive protein and albumin thresholds of 3 mg/L and 35 g/L, respectively. Moreover, receiver operating characteristic curve analyses were executed to find out the optimal PLR and NLR cutoffs. We plotted survival curves and compared them through the use of the Kaplan–Meier method and log-rank test, respectively. Through a Cox proportional hazard model, we identified prognostic variables. We also plotted a nomogram comprising the HS-mGPS and clinicopathological factors and assessed its performance with the concordance index.ResultsThe PLR and NLR cutoffs were 119.34 and 4.51, respectively. We noted an HS-mGPS of 1−2 to be associated with a shorter median overall survival (OS) and disease-fee survival (DFS) compared with an HS-mGPS of 0. Multivariate analysis revealed that an HS-mGPS of 1−2 and an NLR of ≥4.51 were independent risk factors related to poor OS and DFS. The HS-mGPS appeared to have better prognostic effect than did the PLR and NLR, and the combination of the HS-mGPS and NLR appeared to exhibit optimal discriminative ability for OS prognostication. The nomogram based on the HS-mGPS and NLR yielded accurate OS prediction (concordance index = 0.803).ConclusionOur findings suggest that preoperative HS-mGPS is a promising prognostic biomarker of OSCC, and the nomogram comprising the HS-mGPS and NLR provided accurate individualized OSCC survival predictions.

ObjectiveIn individuals with epiglottitis, chronic obstructive pulmonary disease (COPD) is a common comorbidity; however, the impact of COPD under such circumstances is not well documented. Therefore, we performed this population-based study to determine whether, in adults, COPD is a risk factor for epiglottitis.MethodsIn this retrospective matched-cohort study, data obtained from the Taiwan National Health Insurance Research Database were analyzed. We identified all patients newly diagnosed as having COPD in 2000-2011 and performed frequency matching and propensity-score matching for every patient with COPD individually to another patient without a COPD diagnosis. We used epiglottitis occurrence as the study endpoint, and we investigated the hazard ratio of epiglottitis by using the Cox proportional hazards model after adjustment for potential confounders.ResultsIn the frequency matching, the cumulative epiglottitis incidence was significantly higher (p = 0.005) in the COPD cohort. According to the adjusted Cox proportional hazard model, COPD exhibited a significant association with elevated epiglottitis incidence (adjusted hazard ratio: 1.76; 95% confidence interval: 1.15-2.70, p = 0.009). Similar trend was observed in the propensity-score matching analysis (adjusted hazard ratio: 1.50; 95% confidence interval: 0.99-2.29, p = 0.057). Our subgroup analysis revealed COPD to be an epiglottitis risk factor in male patients and those aged 40-64 years.ConclusionsThis is the first nationwide matched-cohort research to examine the association of COPD with epiglottitis. Our results revealed that COPD may be a potential risk factor for epiglottitis; thus, clinicians should be mindful of the potential increased risk of epiglottitis following COPD.

The nasal septal abscess (NSA) is a rare but potentially fatal disease causing intracranial infection. Treatments for NSA include antibiotics, surgical incision and drainage. Diabetes mellitus (DM) is a risk factor for NSA. Therefore, we assessed the pathogenic bacterial composition of NSA in diabetic patients. We analyzed the Chang Gung Memorial Hospital database to collect 79 NSA patients who received surgical incisions and drainage from 2004 to 2015. We divided them into DM and non-DM groups for analysis. We integrated the bacteria cultured from each patient, listed the top three with the highest frequency and divided the bacterial species into facultative anaerobes or aerobes and anaerobes. The microbiological cultures revealed mono-microbial infection in most of the cases. The top three facultative anaerobes or aerobes with the highest frequency of NSA-DM were Klebsiella pneumoniae (37.5%), methicillin-sensitive Staphylococcus aureus (MSSA; 25%) and methicillin-resistant Staphylococcus aureus (MRSA; 12.5%). The top three for NSA-non-DMs were MSSA (24%), MRSA (20%) and Pseudomonas aeruginosa (16%). The top three anaerobes causing NSA were Prevotella intermedia (25%), Peptostreptococcus species (12.5%) and Propionibacterium acnes (12.5%) in DM patients. The top three in non-DM patients were P. intermedia (25%), P. acnes (16.7%) and Fusobacterium nucleatum (12.5%). When treating NSA in diabetic patients, clinicians should choose empirical antibiotics for K. pneumoniae and P. intermedia, and when treating patients with NSA-non-DM, MSSA and P. intermedia should be considered first.

Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike protein and subsequently increase the infectivity of the beta variant. The L452R mutation in the epsilon variant (the B.1.427/B.1.429 variants) also reduced neutralizing activity of monoclonal antibodies. In this study, we discovered that 300 μg/mL GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and wild-type (Wuhan type) RBD spike protein. GB-2 can inhibit the binding between ACE2 and RBD with K417N-E484K-N501Y mutation in a dose-dependent manner. GB-2 inhibited the binding between ACE2 and the RBD with a single mutation (K417N or N501Y or L452R) except the E484K mutation. In the compositions of GB-2, glycyrrhiza uralensis Fisch. ex DC., theaflavin and (+)-catechin cannot inhibit the binding between ACE2 and wild-type RBD spike protein. Theaflavin 3-gallate can inhibit the binding between ACE2 and wild-type RBD spike protein. Our results suggest that GB-2 could be a potential candidate for the prophylaxis of some SARS-CoV-2 variants infection in the further clinical study because of its inhibition of binding between ACE2 and RBD with K417N-E484K-N501Y mutations or L452R mutation.

ObjectivesFor patients with oral cavity squamous cell carcinoma (OSCC), particularly for those with advanced disease, quality of life (QoL) is a key outcome measure. Therefore, we estimated survival-weighted psychometric scores (SWPS), life expectancy (LE), and quality-adjusted LE (QALE) in patients with advanced OSCC.Methods and MaterialsFor estimation of survival function, we enrolled 2313 patients with advanced OSCC diagnosed between January 1, 2007, and December 31, 2013. The patients were followed until death or December 31, 2014. To acquire the QoL data, data from 194 patients were collected by employing the Taiwan Chinese versions of the Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Head and Neck 35 developed by the European Organisation for Research and Treatment of Cancer and the EQ-5D-3L between October 1, 2013, and December 31, 2017. The LE of the patients with OSCC were estimated through linear extrapolation of a logit-transformed curve. SWPS and QALE were determined by integrating the LE and corresponding QoL outcomes.ResultsFor the patients with advanced OSCC, the estimated LE and QALE were 8.7 years and 7.7 quality-adjusted life years (QALYs), respectively. The loss of LE and QALE was 19.0 years and 20.0 QALYs, respectively. The estimated lifetime impairments of swallowing, speech, cognitive functioning, physical functioning, social functioning, and emotional functioning were 8.3, 6.5, 6.5, 6.1, 5.7, and 5.4 years, respectively. The estimated lifetime problems regarding mouth opening, teeth, social eating, and social contact were 6.6, 6.1, 7.5, and 6.1 years, respectively. The duration of feeding tube dependency was estimated to be 1.6 years.ConclusionsPatients with advanced OSCC had an estimated LE of 8.7 years and QALE of 7.7 QALYs. SWPS provided useful information regarding how advanced OSCC affects the subjective assessment of QoL. Our study results may serve as a reference for the allocation of cancer treatment resources.

AimThe aim of our study was to investigate the prognostic value of preoperative advanced lung cancer inflammation index (ALI) and to establish prognostic nomograms for the prediction of survival outcomes in patients with oral cavity squamous cell carcinoma (OSCC).Materials and MethodsA total of 372 patients who received primary curative surgery for OSCC during 2008–2017 at a tertiary referral center were enrolled. We used the receiver operating characteristic curve to determine the optimal cutoff point of ALI. Through a Cox proportional hazards model and Kaplan–Meier analysis, we elucidated the ALI–overall survival (OS) and ALI–disease-free survival (DFS) associations. Prognostic nomograms based on ALI and the results of multivariate analysis were created to predict the OS and DFS. We used the concordance indices (C-indices) and calibration plots to assess the discriminatory and predictive ability.ResultsThe results revealed that the ALI cutoff was 33.6, and 105 and 267 patients had ALI values of

Danshen (Salvia miltiorrhiza Bunge) is broadly utilized in traditional Chinese medicine for lung cancer. However, it’s exact effort and mechanism on lung cancer is fully unclear. In this study, we found that dihydroisotanshinone I (DT), a pure compound extracted from danshen, can inhibit the growth of A549 cells and H460 cells. DT also induced apoptosis and ferroptosis in these lung cancer cells. DT also blocking the protein expression of GPX4 (Glutathione peroxidase 4). For in vivo study, DT treatment can inhibit metastasis of A549 cells in the nude mice model without adverse effects on mice. In conclusion, DT inhibited the growth of lung cancer cells through apoptosis and ferroptosis and inhibited metastasis of A549 cells in the nude mice model. Further studies are warranted to validate the findings of this study.

BackgroundA typical assessment for sarcopenia involves the use of abdominal computed tomography (CT) for calculating the skeletal muscle index (SMI) at the level of the third lumbar vertebra (L3). However, abdominal CT is not regularly performed on patients with head and neck cancer (HNC). We investigated whether masticatory SMI (M-SMI) measurements based on head and neck CT scans can be used to conduct sarcopenia assessments by evaluating whether M-SMI is correlated with L3-SMI.MethodsAbdominal and head and neck CT images of patients with trauma (n = 50) and HNC (n = 52) were analyzed retrospectively. Both manual delineation and threshold selection methods were used to measure cross-sectional areas of masticatory muscles and those of muscles at the L3 level on CT images. Muscle cross-sectional areas were normalized to height squared to calculate SMI, and a multivariate linear regression model was established to evaluate the correlation between the M-SMI and L3-SMI. Receiver operating characteristic curve analysis was used to assess the ability of the M-SMI to identify sarcopenia, and Cox logistic regression was used to identify predictors of sarcopenia.ResultsPatients with HNC had significantly lower M-SMI and L3-SMI than did patients with trauma (p = 0.011 and 0.03, respectively). M-SMI and L3-SMI were strongly correlated (r = 0.901, p < 0.001); in the multivariate model that included sex, the correlation was stronger (r = 0.913, p < 0.001). The associations of sarcopenia with a lower M-SMI (p < 0.001), male sex (p = 0.028), and advanced age (p = 0.011) were significant, and multivariate logistic analysis demonstrated that an M-SMI of ConclusionsM-SMI assessment in routine head and neck CT scans is feasible and can be an alternative for detecting sarcopenia in patients with HNC.

Objectives Patients with uremia are prone to infection; however, end-stage renal disease (ESRD) as a risk factor for acute epiglottitis warrants study. We investigated the risk of severe epiglottitis requiring hospitalisation in patients with ESRD.Setting We conducted a retrospective matched cohort study by using the claims data of Taiwan’s National Health Insurance Research Database.Participants We identified an ESRD cohort with 87 908 patients newly diagnosed in 2000–2013 and underwent dialysis. The non-ESRD cohort comprised patients who had not received a diagnosis of ESRD, and they were matches to the ESRD cohort (1:1) by sex, age, residence urbanisation level, monthly income, and diabetes and hypertension status.Primary and secondary outcome measures The cumulative incidence of epiglottitis at the end of 2013 was analysed with Kaplan-Meier methods and log-rank tests. The HR of epiglottitis was calculated using the Cox proportional hazards model after adjustment for confounding factors.Results The overall epiglottitis incidence rate was 94% greater in the ESRD cohort than in the non-ESRD cohort (10.3 vs 5.3 cases per 100 000 person-years, p=0.002), with an adjusted HR of 1.89 (95% CI: 1.23 to 2.91, p=0.004). In the log-rank analysis, compared with the non-ESRD group, the epiglottitis cumulative incidence was significantly higher in the ESRD group (p=0.003). Epiglottitis did not exhibit an association with higher rates of airway interventions, intensive care unit admissions or longer hospitalisation in patients with ESRD than in controls.Conclusions This nationwide matched cohort study indicated that ESRD patients should be monitored for the risk of severe epiglottitis requiring hospitalisation.

Background Although the C-reactive protein-to-albumin ratio (CAR) can predict poor outcomes in assorted cancers, its prognostic value in oral cavity squamous cell carcinoma (OSCC) remains unclear. We explored the value of preoperative CAR in predicting clinical outcomes in OSCC patients treated with radical surgery. Methods All the recommended cutoff values were defined analyzing receiver operating characteristic curves or overall survival (OS). Dichotomization was performed on the basis of optimal CAR cutoff, and we compared the clinicopathological features between groups. Kaplan–Meier analysis was also performed to compare OS curves between the two groups. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to find the clinical characteristics that were most closely correlated with disease free survival (DFS) and overall survival (OS). A nomogram incorporated CAR and several clinicopathological factors was established to predict prognosis and its accuracy was evaluated using concordance index (c-index). Results In this retrospective study, a total of 326 patients with newly diagnosis of OSCC and received primary surgery between 2008 and 2017 were enrolled. Through the executed ROC curve analyses, the optimal CAR cutoff derived was 0.195 (area under the curve = 0.718, p < 0.001), with this cutoff exhibiting a discrimination ability superior to that of other inflammation-based prognostic scores after comparing the area under curves. Multivariate analysis demonstrated that CAR (≥0.195/

Abstract Background Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. However, remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Despite the increasing understanding of the resistance mechanisms, effective regimens for treating tamoxifen-resistant breast cancer are limited. Antrodia cinnamomea is a traditional medicinal mushroom native only to Taiwan. In this study, we aimed to examine in vitro effect of antrodia cinnamomea in the tamoxifen-resistant cancer. Methods Antrodia cinnamomea was studied for its biological activity against proliferation of tamoxifen-resistant breast cancer by XTT assay. Next, the underlying mechanism was studied by flow cytometry, qPCR and Western’s blotting assay. Results Our results revealed that the ethanol extract of antrodia cinnamomea (AC) can inhibit the growth of breast cancer cells, including MCF-7 cell and tamoxifen-resistant MCF-7 cell lines. Combination treatment with AC and 10− 6 M tamoxifen have the better inhibitory effect on the proliferation of tamoxifen-resistant MCF-7 cells than only AC did. AC can induce apoptosis in these breast cancer cells. Moreover, it can suppress the mRNA expression of skp2 (S-phase kinase-associated protein 2) by increasing the expressions of miR-21-5p, miR-26-5p, and miR-30-5p in MCF-7 and tamoxifen-resistant MCF-7 cells. Conclusions These results suggest that the ethanol extract of antrodia cinnamomea could be a novel anticancer agent in the armamentarium of tamoxifen-resistant breast cancer management. Moreover, we hope to identify additional pure compounds that could serve as promising anti-breast cancer candidates for further clinical trials.

Deep neck infection (DNI) is a lethal emergent condition. Patients with types 1 and 2 diabetes mellitus (T1DM and T2DM, respectively) are predisposed to DNI and have poorer prognoses. The mainstay of the treatment is surgical drainage and antibiotics; however, the pathogenic bacteria of T1DM-DNI have not been studied before. We obtained the data of 8237 patients with DNI who were hospitalized from 2004 to 2015 from the Chang Gung Research Database, which contains multi-institutional medical records in Taiwan. Using diagnostic codes, we classified them into T1DM-DNI, T2DM-DNI, and non-DM-DNI and analyzed their pathogenic bacteria, disease severity, treatment, and prognosis. The top three facultative anaerobic or aerobic bacteria of T1DM-DNI were Klebsiella pneumoniae (KP, 40.0%), Viridans Streptococci (VS, 22.2%), and methicillin-sensitive Staphylococcus aureus (MSSA, 8.9%), similar for T2DM (KP, 32.2%; VS, 23.3%; MSSA, 9.5%). For non-DM-DNI, it was VS (34.6%), KP (9.8%), and coagulase-negative Staphylococci (8.7%). The order of anaerobes for the three groups was Peptostreptococcus micros, Prevotella intermedia, and Peptostreptococcus anaerobius. Patients with T1DM-DNI and T2DM-DNI had higher white blood cell (WBC) counts and C-reactive protein (CRP) levels, more cases of surgery, more cases of tracheostomy, longer hospital stays, more mediastinal complications, and higher mortality rates than those without DM-DNI. Patients in the death subgroup in T1DM-DNI had higher WBC counts, band forms, and CRP levels than those in the survival subgroup. Patients with DM-DNI had more severe disease and higher mortality rate than those without DM-DNI. KP and Peptostreptococcus micros are the leading pathogens for both patients with T1DM-DNI and those with T2DM-DNI. Clinicians should beware of high serum levels of infection markers, which indicate potential mortality.

Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of the head and neck, and their prevalence is rapidly increasing. HNSCCs present a clinical challenge because of their high recurrence rate, therapeutic resistance to radiation and chemotherapy drugs, and adverse effects. Hence, traditional Chinese herbal treatment may be advantageous to therapeutic strategies for HNSCCs. Danshen (Salvia miltiorrhiza), a well-known Chinese herb, has been extensively applied in treatments for various diseases, including cancer, because of its high degree of safety and low rate of adverse effects despite its unclear mechanism. Thus, we aimed to explore the possible anticancer effects and mechanisms of dihydroisotanshinone I (DT), a compound in danshen (extract from danshen), on HNSCCs. Three HNSCCs cell lines were used for in vitro studies, and a Detroit 562 xenograft mouse model was chosen for in vivo studies. Our in vitro results showed that DT could initiate apoptosis, resulting in cell death, and the p38 signaling partially regulated DT-initiated cell apoptosis in the Detroit 562 model. In the xenograft mouse model, DT reduced tumor size with no obvious adverse effect of hepatotoxicity. The present study suggests that DT is a promising novel candidate for anti-HNSCCs therapy.

Abstract Medialization laryngoplasty is the standard surgical treatment for unilateral vocal fold paralysis. This study presents a modified approach in which a thyroid cartilage graft is implanted in medialization laryngoplasty. 22 patients who underwent this approach were included in the study. The results revealed that glottal incompetence and vocal performance were markedly improved following surgery, and the follow-up period ranged from 6 to 74 months (mean, 21.4 months). Acoustic analysis revealed significant improvements in the maximum phonation time (from 3.51 to 7.89 seconds, p

Abstract Background Uremia is likely a risk factor for deep neck infection (DNI). However, only a few relevant cases have been reported, and evidence sufficient to support this hypothesis is lacking. The aim of the study is to investigate the effects of end-stage renal disease (ESRD) on DNI. Methods We used the database of the Registry for Catastrophic Illness Patients (RFCIP), a subset of the National Health Insurance Research Database (NHIRD) in Taiwan, to conduct a retrospective follow-up study. Between 1997 and 2013, a total of 157,340 patients in Taiwan with ESRD who received dialysis were registered in the RFCIP, whom were matched with a database consisting of 1,000,000 randomly selected patients who represented the national population, to conduct the follow-up study for investigating the incidence of DNI in the ESRD and control cohorts. Results In the ESRD group, 280 DNIs were identified with an incidence rate of 43 per 100,000 person-years. In the comparison group, 194 DNIs were identified with an incidence rate of 20 per 100,000 person-years. The incidence rate ratio was 2.16 (p

Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is definite clinical effort and mechanism on breast cancer is unclear. In our study, we used the real-world database to investigate in vivo protective effort of danshen in the breast cancer patients through using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). In vitro, human breast cancer cells (MCF-7 cells and MDA-MB-231 cells) were used to investigate the effect and the underlying mechanism through XTT assay, flow cytometry, glutathione peroxidase (GPX) activity assay, GSH (reduced glutathione)/GSSG (oxidized glutathione), malondialdehyde (MDA), and western blot analysis. The in vivo effect was investigated through a xenograft nude mouse model. We found that dihydroisotanshinone I (DT), a pure compound present in danshen, can inhibit the growth of breast carcinoma cells, including MCF-7 cells and MDA-MB-231 cells. Moreover, DT induced apoptosis and ferroptosis in these breast cancer cells. DT also repressed the protein expression of GPX4 (Glutathione peroxidase 4). For in vivo study, DT treatment also significantly inhibited the final tumor volume without adverse effects in a xenograft nude mouse model. In conclusion, danshen has protective efforts in breast cancer patients, which could be attributed to DT through inducing apoptosis and ferroptosis of breast cancer cells.

ObjectiveWhether dysrhythmia is a risk factor of sudden sensorineural hearing loss (SSNHL) remains unclear. In this study, we aimed to investigate the risk of developing SSNHL among patients with dysrhythmia in different age and gender groups by using population-based data in Taiwan.MethodsWe conducted a matched cohort study by analyzing data between January 2000 and December 2013 obtained from the Taiwan National Health Insurance Research Database. 41,842 newly diagnosed dysrhythmia patients and 83,684 comparison subjects without dysrhythmia were selected from claims. The incidence of sudden sensorineural hearing loss at the end of 2013 was determined in both groups. Univariate and multivariate logistic regression analyses were used to investigate the risk of SSNHL among patients with dysrhythmia.ResultsThe incidence of SSNHL was 1.30-fold higher in the dysrhythmia group compared with the control group (53.2 versus 40.9 per 100,000 person-years), and using Cox proportional hazard regressions, the adjusted hazard ratio (HR) was 1.40 (95% confidence interval [CI], 1.15-1.70). Gender-stratified analysis revealed a significantly higher risk of SSNHL in patients with dysrhythmia than in those without dysrhythmia for both men and women (HR = 1.34, 95% CI = 1.02-1.76, P = 0.039, HR = 1.35, 95% CI = 1.02-1.78, P = 0.035, respectively). Age-stratified analysis revealed remarkable associations between dysrhythmia and SSNHL among those aged less than 40 years and more than 65 years (HR = 2.18, 95% CI = 1.03-4.64, P = 0.043 and HR = 1.54, 95% CI = 1.14-2.09, P = 0.006, respectively).ConclusionsOur findings support dysrhythmia as an independent risk factor for SSNHL. Based on the study results, clinicians managing patients with dysrhythmia should be aware of the increased risk of developing SSNHL, especially among patients aged 65 years, and counsel patients to seek medical advice immediately if they experience any acute change in their hearing ability.

(1) Background: A high volume of chylous leakage (>1 L/day) is a potentially lethal complication after neck dissection. However, a strategic treatment for when the leakage progresses from high to massive (>4 L/day) is lacking. (2) Methods: The PubMed database was searched for articles on neck dissection–associated chylous leakage. Nine articles that included 14 cases with >1 L/day chylous leakage (CL) were analyzed. (3) Results: Of the nine patients with 1–4 L/day CL, three were successfully managed with conservative treatment, two with thoracic ductal ligation, three with ductal embolization, and one with local repair with a strap muscle flap. Of the remaining five cases with >4 L/day chylous leakage, three were successfully treated with the pectoralis major myocutaneous flap (PMMF) and one was successfully treated with thoracic ductal ligation and one case died. (4) Conclusions: In this review, when leakage was >4 L/day, the aforementioned interventions were ineffective, but applying the PMMF could rescue the intractable complication. We propose a strategic treatment for high (1–4 L/day) and massive (>4 L/day) chylous leakage.

(1) Background: Post-transplant lymphoproliferative disorder (PTLD) is a hematological disease and occurs because of immunosuppression after organ transplantation. Only a few studies have reported PTLD in the nasopharynx. In most cases, PTLD developed after solid organ transplantation, and cases of PTLD after bone marrow transplantation, are uncommon. (2) Case presentation: We report the case of a 40-year-old woman with myelodysplastic disorder who underwent hematopoietic stem cell transplantation (HSCT). After 3 months, she developed low-grade fever, progressive nasal obstruction, and bloody rhinorrhea. Endoscopy revealed a mass completely occupying the nasopharynx. A polymorphic PTLD was diagnosed on the basis of histopathological examination results. Reduction in immunosuppression and low-dose radiotherapy were prescribed for treatment. After a 3-year follow-up, no recurrence of PTLD or myelodysplastic disorder was detected. (3) Conclusions: While nasopharyngeal PTLD is rare, a routine examination of the nasopharynx should be considered in the post-transplant follow-up of patients for early detection and treatment of PTLD.

Allergic rhinitis (AR) is correlated with diseases including allergic laryngitis, chronic obstructive pulmonary disease (COPD), asthma, and chronic rhinosinusitis (CRS). The unified airway model suggests that inflammation can spread in both lower and upper respiratory tracts. Moreover, some voice problems—laryngeal edema, dysphonia, and vocal nodules—have been associated with AR. We examined the association between AR and laryngeal pathology. We investigated 51,618 patients with AR between 1 January 1997 and 31 December 2013, along with 206,472 patients without AR matched based on age, gender, urbanization level, and socioeconomic status at a 1:4 ratio. We followed patients up to the end of 2013 or their death. The occurrence of laryngeal pathology was the primary outcome. Individuals with AR had a 2.43 times higher risk of laryngeal pathology than the comparison cohort group (adjusted HR: 2.43, 95% CI: 2.36–2.50, p < 0.001). Patients diagnosed as having AR exhibited higher comorbidity rates, including of asthma, COPD, CRS, gastroesophageal reflux disease, and nasal septum deviation, than those of the comparison cohort. Our results strongly indicate that AR is an independent risk factor for laryngeal pathology. Therefore, when treating AR and voice problems, physicians should be attuned to possible laryngeal pathology.

(1) Background: Medialization laryngoplasty with autologous thyroid cartilage (MLATC) is a surgical treatment for glottal closure insufficiency (GCI) resulted from unilateral vocal fold paralysis/paresis (UVFP) and vocal fold atrophy. We aimed to survey the influence of patient-related factors on the outcomes after MLATC. (2) Methods: The study enrolled 35 patients with GCI who underwent MLATC. Patient voice data were recorded before and after MLATC by using multiple acoustic parameters and subjective assessment in a computerized speech laboratory. GCI patients were characterized into subgroups based on three factors: age, ≥60 vs.

Background: Vocal fold nodules (VFNs) are a challenge for otolaryngologists. Glottal area (GA) waveform analysis is an examination method used for assessing vocal fold vibration and function. However, GA in patients with VFNs has rarely been studied. This study investigated the maximum and minimum GA in VFN patients using modern waveform analysis combining ImageJ software and videostroboscopy. Methods: This study enrolled 42 patients newly diagnosed with VFN, 15 of whom received voice therapy and 27 of whom underwent surgery. Acoustic parameters and maximum phonation time (MPT) were recorded, and patients completed the Chinese Voice Handicap Index-10 (VHI-C10) before and after treatment. After videostroboscopy examination, the maximum and minimum GAs were calculated using ImageJ software. The GAs of patients with VFNs before and after surgery or voice therapy were analyzed. Results: The MPTs of the patients before and after voice therapy or surgery did not change significantly. VHI-C10 scores decreased after voice therapy but the decrease was nonsignificant (14.0 ± 8.44 vs. 9.40 ± 10.24, p = 0.222); VHI-C10 scores were significantly decreased after surgery (22.53 ± 7.17 vs. 12.75 ± 9.84, p = 0.038). Voice therapy significantly increased the maximum GA (5.58 ± 2.41 vs. 8.65 ± 3.17, p = 0.012) and nonsignificantly decreased the minimum GA (0.60 ± 0.73 vs. 0.21 ± 0.46, p = 0.098). Surgery nonsignificantly increased the maximum GA (6.34 ± 3.82 vs. 8.73 ± 5.57, p = 0.118) and significantly decreased the minimum GA (0.30 ± 0.59 vs. 0.00 ± 0.00, p = 0.036). Conclusion: This study investigated the GA of patients with VFNs who received voice therapy or surgery. The findings indicated that voice therapy significantly increased maximum GA and surgery significantly decreased minimum GA. GA analysis could be applied to evaluate the efficacy of voice therapy, and it may help physicians to develop precise treatment for VFN patients (either by optimizing voice therapy or by performing surgery directly).

OBJECTIVE:Studies have revealed that 3.5%-26.6% of patients with epiglottitis have comorbid diabetes mellitus (DM). However, whether preexisting DM is a risk factor for acute epiglottitis remains unclear. In this study, our aim was to explore the relationship between preexisting DM and acute epiglottitis in different age and sex groups by using population-based data in Taiwan. METHODS:We analyzed data between January 2000 and December 2013 obtained from the Taiwan National Health Insurance Research Database. The case group consisted of 2,393 patients with acute epiglottitis. The control group comprised 9,572 individuals without epiglottitis, frequency matched by sex, age, urbanization level, and income. Underlying DM was retrospectively assessed in the cases and controls. Univariate and multivariate logistic regression analyses were used to investigate the associations between underlying DM and acute epiglottitis. RESULTS:Of the 2,393 patients, 180 (7.5%) had preexisting DM, whereas only 530 (5.5%) of the 9,572 controls had preexisting DM. Multivariate logistic regression analyses indicated that preexisting DM was significantly associated with acute epiglottitis (adjusted odds ratio [aOR] = 1.42, 95% confidence interval [CI] = 1.15-1.75, P = 0.004). Subgroup analysis showed that the association between DM and epiglottitis remained significant for men (aOR = 1.57, 95% CI: 1.19-2.08, p = 0.002) but not for women. Age-stratified analysis revealed a significant association between DM and acute epiglottitis in patients aged 35-64 years. Use of anti-diabetic agents was not significantly associated with the development of acute epiglottitis among diabetic patients, including oral hypoglycemic agents (OHA) alone (aOR = 0.88, 95% CI = 0.53-1.46, p = 0.616), and OHA combined with insulin/ insulin alone (aOR = 1.30, 95% CI = 0.76-2.22, p = 0.339). The association between presence of diabetes complications and the occurrence of acute epiglottitis was also not significant among diabetic patients in this study setting (aOR = 0.86, 95% CI = 0.59-1.26, p = 0.439). CONCLUSIONS:The results of our large-scale population-based case-control study indicate that preexisting DM is one of the possible factors associated with the development of acute epiglottitis. Physicians should pay attention to the symptoms and signs of acute epiglottitis in DM patients, particularly in men aged 35-64 years.