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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.

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.

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).

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.