The Effect and Mechanism of Astragalus Polysaccharides on T Cells and Macrophages in Inhibiting Prostate Cancer.

BACKGROUND: The impact and underlying mechanisms of astragalus polysaccharide (APS) on prostate cancer, particularly its role in immunomodulation, remain inadequately elucidated. METHODS: This study employed the XTT assay for assessing proliferation in prostate cancer cells and macrophages. T cell proliferation was determined using the Carboxyfluorescein diacetate succinimidyl ester labeling assay. APS's effect on T cells and macrophages was scrutinized via flow cytometry, Western blot analysis, ELISA, quantitative PCR and cytokine membrane arrays. The effect of APS on interaction between PD-L1 and PD-1 was investigated by the PD-L1/PD-1 homogeneous assay. Additionally, the impact of conditioned medium from T cells and macrophages on PC-3 cell migration was explored through migration assays. RESULTS: It was observed that APS at concentrations of 1 and 5 mg/mL enhanced the proliferation of CD8+ T cells. At a concentration of 5 mg/mL, APS activated both CD4+ and CD8+ T cells, attenuated PD-L1 expression in prostate cancer cells stimulated with interferon gamma (IFN-γ) or oxaliplatin, and moderately decreased the population of PD-1+ CD4+ and PD-1+ CD8+ T cells. Furthermore, APS at this concentration impeded the interaction between PD-L1 and PD-1, inhibited the promotion of prostate cancer migration mediated by RAW 264.7 cells, THP-1 cells, CD4+ T cells, and CD8+ T cells, and initiated apoptosis in prostate cancer cells treated with conditioned medium from APS (5 mg/mL)-treated CD8+ T cells, RAW 264.7 cells, or THP-1 cells. CONCLUSION: The findings indicate a potential role of 5 mg/mL APS in modulating the PD-1/PD-L1 pathway and influencing the immune response, encompassing T cells and macrophages. Consequently, further in vivo research is recommended to assess the efficacy of APS.

Induction of ferroptosis and apoptosis in endometrial cancer cells by dihydroisotanshinone I.

Danshen, also known as Salvia miltiorrhiza, is a medicinal herb used in traditional Chinese medicine. Its potential impact on endometrial cancer has not been thoroughly investigated. This study aimed to examine the effect of dihydroisotanshinone I (DT), a compound found in Danshen, on the viability of ARK1 and ARK2 endometrial cancer cells and its mechanisms. The results showed that 10 µM DT inhibited cell viability of ARK1 and ARK2 cells by inducing apoptosis and ferroptosis, which was achieved by blocking the expression of GPX4. In vivo experiments using a xenograft nude mouse model indicated that DT treatment significantly reduced tumor volume without causing any adverse effects. These findings suggest that DT may be a potential therapeutic agent for inhibiting endometrial cancer cell viability, but further research is needed to confirm these results.

The anti-SARS-CoV-2 effect and mechanism of Chiehyuan herbal oral protection solution.

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.

Dihydroisotanshinone I and BMAL-SIRT1 Pathway in an In Vitro 6-OHDA-Induced Model of Parkinson's Disease.

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.

6-shogaol is a potential treatment for Head and Neck Squamous Cell Carcinoma.

Objective: Natural products in diet have shown a potential role in the prevention and treatment of cancer. Ginger (Zingiber officinale Roscoe) is a great candidate because of its properties of anti-inflammatory, antioxidant, and anti-cancer, but little is known about its effect on head and neck cancer. 6-Shogaol is an active compound derived from Ginger. Thus, this study aimed to investigate the possible anticancer effects of 6-shogaol, a major ginger derivate, on head and neck squamous cell carcinomas (HNSCCs) and the underlying mechanisms. Material and Methods: Two HNSCC cell lines, SCC4 and SCC25, were used in this study. Both SCC4 and SCC25 cells were kept as control or treated with 6-shogaol for 8 and 24 hours and then the cell apoptosis and cell cycle progression of treated cells were examined by PI and Annexin V-FITC double stain and flow cytometry analysis. The Cleaved caspase 3, phosphorylations of ERK1/2 and p38 kinases were examined by Western blot analysis. Results: The results showed that 6-shogaol significantly initiated the G2/M phase arrest of the cell cycle and apoptosis to inhibit the survival of both cell lines. Moreover, these responses could be regulated by ERK1/2 and p38 signaling. And, finally, we also demonstrated that 6-shogaol could enhance the cytotoxicity of cisplatin in HNSCC cells. Conclusion: Our data provided new insights to understand the potential pharmaceutical efficacy of a ginger derivate, 6-shogaol, in antagonizing HNSCC survival. The present study suggests that 6-shogaol is a potential novel candidate for anti-HNSCCs therapy.

The Role of MRE11 in the IL-6/STAT3 Pathway of Lung Cancer Cells.

MRE11 is a pivotal protein for ATM activation during double-strand DNA break. ATM kinase activations may act as lung cancer biomarkers. The IL-6/STAT3 pathway plays an important role in tumor metastasis, including lung cancer. However, the mechanism between MRE11 and the IL-6/STAT3 pathway is still unclear. In this study, we discovered that MRE11 can interact with STAT3 under IL-6 treatment and regulate STAT3 Tyr705 phosphorylation. After the knockdown of MRE11 in lung cancer cells, we discovered that IL-6 or the conditional medium of THP-1 cells can induce the mRNA expression of STAT3 downstream genes, including CCL2, in the control cells, but not in MRE11-knockdown lung cancer cells. Moreover, CCL2 secretion was lower in MRE11-knockdown lung cancer cells than in control cells after treatment with the conditional medium of RAW264.7 cells. In addition, MRE11 deficiency in lung cancer cells decreases their ability to recruit RAW 264.7 cells. Furthermore, MRE11 is a potential target for lung cancer therapy.

The Bacterial Compositions of Nasal Septal Abscess in Patients with or without Diabetes.

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.

Nasal irrigation with licorice extract (Glycyrrhiza glabra) in treating nasal polyps by reducing fibroblast differentiation and extracellular matrix production in TGF-ß1-stimulated nasal polyp-derived fibroblasts by inhibiting the MAPK/ERK-1/2 pathway - an in vitro and in clinic study.

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-ß1-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-ß1, 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 difference in pathogenic bacteria between chronic rhinosinusitis in patients with and without Sjogren's syndrome: a retrospective case-control study.

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.

Potential inhibitor for blocking binding between ACE2 and SARS-CoV-2 spike protein with mutations.

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).

Pathogens and Prognosis of Deep Neck Infection in End-Stage Renal Disease Patients.

OBJECTIVES/HYPOTHESIS: To examine the pathogenic bacterial spectra and prognosis of deep neck infection (DNI) in end-stage renal disease (ESRD) patients. STUDY DESIGN: Retrospective study. METHODS: Patients diagnosed with DNI between 2004 and 2015 in Chang Gung Memorial Hospital were enrolled and divided into three groups, namely ESRD-DNI, chronic kidney disease (CKD)-DNI, and non-CKD-DNI. Differences in pathogenic bacteria, treatment, and prognosis were compared across the three groups. RESULTS: The bacterial spectra differed among the three groups. The main three facultative anaerobic or aerobic bacteria causing ESRD-DNIs were methicillin-resistant Staphylococcus aureus (MRSA; 25.4%), methicillin-susceptible S. aureus (MSSA; 14.1%), and Klebsiella pneumoniae (KP; 12.7%). For CKD-DNIs, they were KP (23.5%), Viridans streptococci (VS; 23.5%), and MSSA (14.7%). For non-CKD-DNIs, they were VS (31.7%), KP (17.2%), and coagulase-negative staphylococci (8.0%). Compared with the other groups, the ESRD-DNI group had higher white blood cell and C-reactive protein levels, longer hospital stays, more frequent admissions to the intensive care unit, more mediastinal complications, and a significantly higher mortality rate. CONCLUSIONS: The ESRD-DNI group exhibited more severe disease activity and higher mortality compared with those of the CKD-DNI and non-CKD-DNI groups. MRSA was the leading pathogen for patients with ESRD-DNI. Physicians must implement strategies for the early detection of MRSA to accurately prescribe antibiotics and prevent nosocomial transmission. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1403-1409, 2022.

The Pathogenic Bacteria of Deep Neck Infection in Patients with Type 1 Diabetes, Type 2 Diabetes, and Without Diabetes from Chang Gung Research Database.

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.

GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2.

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.

Dihydroisotanshinone I as a Treatment Option for Head and Neck Squamous Cell Carcinomas.

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.

High Risk of Peritonsillar Abscess in End-Stage Renal Disease Patients: A Nationwide Real-World Cohort Study.

BACKGROUND: Peritonsillar abscess (PTA) is an infectious emergency in the head and neck, and patients with end-stage renal disease (ESRD) have an immunocompromised status. However, no relevant research has focused on the ESRD-PTA relationship. This study explored PTA in ESRD patients and their prognosis. METHODS: We identified 157,026 patients diagnosed as having ESRD over January 1997 to December 2013 from Taiwan's National Health Insurance Research Database (NHIRD). Each patient with ESRD (hereafter, patients) was matched with one control without chronic kidney disease (CKD; hereafter, controls) by sex, age, urbanization level, and income. Next, PTA incidence until death or the end of 2013 was compared between the two groups, and the relative risk of PTA was analyzed using a multiple logistic regression model. RESULTS: The patients had a significantly higher PTA incidence than did the controls (incidence rate ratio: 2.02, 95% confidence interval [CI]: 1.40-2.91, p < 0.001). The Kaplan-Meier analysis revealed that the patients had a higher cumulative incidence of PTA than did the controls (p < 0.001). In Cox regression analysis, the patients had nearly twofold higher PTA risk (adjusted hazard ratio [HR]: 1.98, 95% CI: 1.37-2.86, p < 0.001). The between-group differences in the PTA-related hospital stay length (8.1 ± 10.3 days in patients and 5.7 ± 4.6 days in controls, p = 0.09), consequent deep-neck infection complication (4.2% in patients and 6.3% in controls, p = 0.682), and mortality (0.0% in both groups) were nonsignificant. Conclusions: Although ESRD does not predict a poor prognosis of PTA, it is an independent PTA risk factor.

Dihydroisotanshinone I induced ferroptosis and apoptosis of lung cancer cells.

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.

Nasal irrigation with Glycyrrhiza glabra extract for treatment of allergic rhinitis - A study of in vitro, in vivo and clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza glabra, a family of licorice and a traditional Chinese medicine with sweet taste and favorable smell, has anti-inflammatory, anti-allergic and immunomodulatory functions. AIM OF THE STUDY: We developed a licorice extract (LE) by using glycyrrhiza glabra and administered it through nasal irrigation to treat allergic rhinitis (AR). MATERIALS AND METHODS: LE was prepared into extract powder, and the anti-inflammatory effect of the LE was evaluated by calcium ionophore-induced activated mast cell model (in vitro). Then, local passive anaphylaxis assays were applied to investigate the anti-IgE-mediated allergic reaction of the LE in mice (in vivo). A developed LE was administered through nasal irrigation to treat AR in clinic settings. A total of 60 participants diagnosed with AR were included in this clinical trial; they were randomly assigned to three interventions: licorice nasal irrigation (LNI), corticosteroid nasal irrigation (CNI), and saline nasal irrigation (SNI). They performed nasal irrigation once a day for 1 month. Both subjective questionnaires (22-item Sino-Nasal Outcome Test [SNOT-22] and visual analog scale [VAS]) and objective examinations (acoustic rhinometry and nasal endoscopy) were used for effectiveness assessments. RESULTS: All three interventions could improve SNOT-22 scores, but the effects of LNI and CNI were more significant. According to VAS scores for nasal blockage, rhinorrhea, sneezing, nasal pruritus, postnasal discharge, and olfactory disturbance, the effect of LNI was superior to those of CNI and SNI. The results of rhinometry revealed that LNI significantly improved nasal resistance. Endoscopic analysis showed that both LNI and CNI, but not SNI, could significantly improve turbinate hypertrophy. Moreover, the best procedural comfort was found for LNI, which had no side effects or complications during the trial. CONCLUSIONS: LNI is a natural, safe, and innovative therapy that can effectively treat AR. Its effect is superior to those of CNI and SNI, and it has greatly improved procedural comfort.

Type 2 Diabetes Mellitus Increases Peritonsillar Abscess Susceptibility: Real-World Evidence.

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; P<0.001); moreover, PTA incidence was higher at 1 to 5 years after T2DM diagnosis than at <1 and >5 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<0.001). Patients with a higher adapted Diabetes Complications Severity Index (aDCSI) had higher PTA risk than those with a lower aDCSI (aHRs: 2.17 for aDCSI ≥1, P=0.006 and 1.81 for aDCSI=0, P=0.002). T2DM patients with a high aDCSI (≥1) had a nonsignificantly longer hospitalization duration and a higher rate of DNI complications than did those with a low aDCSI (=0). CONCLUSION: In patients with T2DM, PTA incidence was relatively high, and it increased with T2DM severity. Moreover, T2DM patients should be particularly careful about PTA within 1 to 5 years after the diagnosis, and physicians should keep in mind that the prognosis of PTA was correlated with T2DM severity.

Patients with comorbid rheumatoid arthritis are predisposed to peritonsillar abscess: real-world evidence.

PURPOSE: The peritonsillar abscess (PTA)-rheumatoid arthritis (RA) association remains unclear. Here, the effects of RA on PTA incidence and prognosis are elucidated. METHODS: We compared PTA incidence and prognosis of 30,706 RFCIP-registered patients with RA (RA cohort) with matched individuals without RA from another database of 1 million randomly selected people representing Taiwan's population (non-RA cohort). RESULTS: The RA cohort had significantly higher PTA incidence [incidence rate ratio (IRR) (95% CI) 1.73 (1.10-2.71), P = 0.017) and cumulative incidence (P = 0.016, Kaplan-Meier curves). Cox regression analyses demonstrated RA cohort to have an estimated 1.72-fold increased PTA risk (95% CI 1.09-2.69, P = 0.019). PTA was more likely within the first 5 years of RA diagnosis (for < 1, 1-5, and ≥ 5 postdiagnosis years, IRRs: 2.67, 2.31, and 1.10, respectively, and P = 0.063, 0.021, and 0.794, respectively; average onset duration: 4.3 ± 3.3 years after RA diagnosis). PTA increased length of hospital stay significantly and risk of complication with deep neck infection nonsignificantly [6.5 ± 4.5 vs 4.6 ± 2.8 days (P = 0.045) and 18.52% vs 7.81% (P = 0.155), respectively]. Moreover, RA-cohort patients not receiving RA therapy exhibited 5.06-fold higher PTA risk than those receiving RA-related therapy (95% CI 1.75-14.62, P = 0.003). CONCLUSIONS: In patients with RA, PTA incidence is the highest within 5 years of RA diagnosis, and RA therapy is essential for reducing PTA risk. LEVEL OF EVIDENCE: 4.

Traditional Chinese Medicine Enhances Survival in Patients with Gastric Cancer after Surgery and Adjuvant Chemotherapy in Taiwan: A Nationwide Matched Cohort Study.

BACKGROUND: Gastric cancer remains a major cancer globally. More than half of patients with gastric cancer undergo surgery in Taiwan; however, few large nationwide studies have investigated the effects of traditional Chinese medicine (TCM) on gastric cancer management after surgery. This study aimed to evaluate the effect of TCM on patients with gastric cancer following surgery and adjuvant chemotherapy in Taiwan and its prescription trends. METHODS AND MATERIALS: The cohort sampling data set was obtained from the Registry of Catastrophic Illness Patient Database, a research database of patients with severe illnesses from the National Health Insurance Research Database, Taiwan. Patients who had received a new diagnosis of gastric cancer and had undergone surgery were enrolled. We matched TCM users and nonusers at a ratio of 1 : 3 based on the propensity score, and TCM users were also grouped into short-term and long-term users. RESULTS: The number of TCM users and nonusers was 1701 and 5103 after applying the propensity score at a ratio of 1 : 3. Short-term users and long-term TCM users were independently associated with a decreased risk of death with HRs of 0.59 (95% confidence interval (CI), 0.55-0.65) and 0.41 (95% CI, 0.36-0.47), respectively, compared with TCM nonusers. We also obtained similar results when we adjusted for covariates in the main model, as well as each of the additional listed covariates. We also observed similar HR trends in short-term users and long-term TCM users among men and women aged <65 years and ≥65 years. The most commonly prescribed single herb and herbal formula in our cohort were Hwang-Chyi (Radix Hedysari; 11.8%) and Xiang-Sha-Liu-Jun-Zi-Tang (15.5%), respectively. CONCLUSION: TCM use was associated with higher survival in patients with gastric cancer after surgery and adjuvant chemotherapy. TCM could be used as a complementary and alternative therapy in patients with gastric cancer after surgery and adjuvant chemotherapy.