Association between serum cytokines and timeframe for conversion from clinical high-risk to psychosis.

AIM: Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high-risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. METHODS: We enrolled 53 individuals with CHR who completed a 5-year follow-up with a confirmed conversion to psychosis. Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1-year. Correlation and quantile regression analyses were performed. RESULTS: The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF-α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF-α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM-CSF levels below the 0.5 quantile, IL-10 levels below the 0.3 quantile, IL-2 levels below the 0.25 quantile, IL-6 levels between the 0.65 and 0.75 quantiles, TNF-α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL-10 and IL-2, and significant group effects for changes in IL-2 and TNF-α. CONCLUSIONS: Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles.

Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment.

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins. In recent years, toxins have been widely used as warheads for antibody‒drug conjugates (ADCs) due to their efficient killing activity against various cancer cells. Although ADCs confer certain targeting properties to the toxins, low drug loading capacity, possible immunogenicity, and other drawbacks also limit the potential application of ADCs. Recently, non-ADC delivery strategies for toxins have been extensively investigated. To further understand the application of toxins in anti-tumor, this paper provided an overview of prodrugs, nanodrug delivery systems, and biomimetic drug delivery systems. In addition, toxins and their combination strategies with other therapies were discussed. Finally, the prospect and challenge of toxins in cancer treatment were also summarized.

Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability.

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.

Serum Levels of Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in the Subtypes of Clinical High Risk Individuals: A Prospective Cohort Study.

Introduction: Numerous studies have established the roles of inflammation and angioneurins in the pathogenesis of schizophrenia (SCZ). This study aimed to compare the serum levels of tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in patients at clinical high risk (CHR) for psychosis or SCZ at baseline and one year after treatment. Methods: A total of 289 CHR participants from the Shanghai At Risk for Psychosis Extended Program (SHARP) were tracked for a year. They were divided into two and four subtypes based on symptom severity according to the Structured Interview for Prodromal Syndromes (SIPS) and received standard medical care. At baseline and one-year follow-up, TNF-α and VEGF were detected using enzyme-linked immunosorbent assay, and pathological features were assessed using the Global Assessment of Function (GAF) score. Results: Baseline TNF-α levels did not differ significantly, while VEGF levels were lower in patients with more severe symptoms. VEGF showed a negative correlation with negative features, both overall (r = -0.212, p = 0.010) and in the subgroup with higher positive scores (r = -0.370, p = 0.005). TNF-α was positively correlated with negative symptoms in the subgroup with higher negative scores (r = 0.352, p = 0.002). A three-way multivariate analysis of variance demonstrated that participants in Subtype 1 of positive or negative symptoms performed better than those in Subtype 2, with significant main effects and interactions of group and both cytokines. Discussion: TNF-α and VEGF levels are higher and lower, respectively, in CHR patients with more severe clinical symptoms, particularly negative symptoms, which point to a worsening inflammatory and vascular status in the brain.

[A multi-center observation of the therapeutic efficacy of Bencycloquidium bromide in the treatment of seasonal allergic rhinitis with predominant symptoms of rhinorrhea].

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.

Artificial Intelligence and Machine (Deep) Learning in Otorhinolaryngology: A Bibliometric Analysis Based on VOSviewer and CiteSpace.

BACKGROUND: Otorhinolaryngology diseases are well suited for artificial intelligence (AI)-based interpretation. The use of AI, particularly AI based on deep learning (DL), in the treatment of human diseases is becoming more and more popular. However, there are few bibliometric analyses that have systematically studied this field. OBJECTIVE: The objective of this study was to visualize the research hot spots and trends of AI and DL in ENT diseases through bibliometric analysis to help researchers understand the future development of basic and clinical research. METHODS: In all, 232 articles and reviews were retrieved from The Web of Science Core Collection. Using CiteSpace and VOSviewer software, countries, institutions, authors, references, and keywords in the field were visualized and examined. RESULTS: The majority of these papers came from 44 nations and 498 institutions, with China and the United States leading the way. Common diseases used by AI in ENT include otosclerosis, otitis media, nasal polyps, sinusitis, and so on. In the early years, research focused on the analysis of hearing and articulation disorders, and in recent years mainly on the diagnosis, localization, and grading of diseases. CONCLUSIONS: The analysis shows the periodical hot spots and development direction of AI and DL application in ENT diseases from the time dimension. The diagnosis and prognosis of otolaryngology diseases and the analysis of otolaryngology endoscopic images have been the focus of current research and the development trend of future.

Association of Attenuated Niacin Response With Inflammatory Imbalance and Prediction of Conversion to Psychosis From Clinical High-risk Stage.

Objective: Attenuated niacin responses and changes in cytokine levels have been reported in schizophrenia. However, prior studies have typically focused on schizophrenia, and little is known about the association between niacin response and inflammatory imbalance in clinically high-risk psychosis (CHR). This study aimed to assess the niacin response to inflammatory imbalance for association with conversion to psychosis within 2 years.Methods: A prospective case-control study was performed to assess the niacin response and interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α levels in 60 CHR individuals and 60 age- and sex-matched healthy controls (HC) from May 2019 to December 2021. Participants with CHR were identified using the Structured Interview for Prodromal Syndromes. The niacin-induced responses were measured using laser Doppler flowmetry. From the dose-response curves, the log-transferred concentration of methylnicotinate required to elicit a half-maximal blood flow response (LogEC50) and maximal minus minimal blood flow response (Span) values were calculated for each subject. Serum cytokine levels were measured using enzyme-linked immunosorbent assay. Individuals with CHR were then divided into converters (CHR-C, n = 15) and non-converters (CHR-NC, n = 45) to psychosis based on their 2-year follow-up clinical status.Results: The CHR group exhibited significantly higher LogEC50 (t = 3.650, P < .001) and Span (t = 2.657, P = .009) values than the HC group. The CHR-C group exhibited a significantly shorter Span (t = 4.027, P < .001) than the CHR-NC group. The LogEC50 showed a trend toward significance (t = 1.875, P = .066). None of the cytokine levels were significant. The conversion outcome can therefore be predicted by applying LogEC50 (P = .049) and Span (P < .001). The regression model with variables of LogEC50, Span, family history, and scores of positive symptoms showed good discrimination of subsequent conversion to psychosis and achieved a classification accuracy of 91.7%. The decreased LogEC50 in the CHR-C group was significantly correlated with the increased IL-1ß/IL-10 ratio (Spearman ρ = -0.600, P = .018), but this correlation was nonsignificant in the CHR-NC group.Conclusions: Our findings indicate a significant association between niacin response and psychosis conversion outcomes in individuals with CHR. Compared with peripheral inflammatory cytokines, the niacin response can better predict conversion, although there may be an intersection between the two in biological mechanisms.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Serum angioneurin levels following electroconvulsive therapy for mood disorders.

OBJECTIVES: The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted "angioneurins") that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD. METHODS: A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no-ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor-2, nerve growth factor (NGF), and insulin-like growth factor-1 levels in blood samples were performed at baseline and week 8. RESULTS: Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p = 0.002). No significant changes in angioneurin levels were observed in the no-ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction. CONCLUSIONS: This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.

Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis.

INTRODUCTION: Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). METHODS: We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. RESULTS: The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, p = 0.010; IL-2, p = 0.023; IL-6, p = 0.012) and HC (IL-6: p = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (p = 0.028), and IL-6 levels tended toward significance (p = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (p = 0.017) and VEGF (p = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (F = 4.502, p = 0.037, effect size (η2) = 0.051), a group effect related to IL-1ß (F = 4.590, p = 0.036, η2 = 0.062), and IL-2 (F = 7.521, p = 0.011, η2 = 0.212), but no time × group effect. DISCUSSION: Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

Serum complement proteins rather than inflammatory factors is effective in predicting psychosis in individuals at clinical high risk.

Immunological/inflammatory factors are implicated in the development of psychosis. Complement is a key driver of inflammation; however, it remains unknown which factor is better at predicting the onset of psychosis. This study aimed to compare the alteration and predictive performance of inflammation and complement in individuals at clinical high risk (CHR). We enrolled 49 individuals at CHR and 26 healthy controls (HCs). Twenty-five patients at CHR had converted to psychosis (converter) by the 3-year follow-up. Inflammatory cytokines, including interleukin (IL)-1ß, 6, 8, 10, tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor levels, and complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H) were measured by enzyme-linked immunosorbent assay at baseline. Except for TNF- alpha, none of the inflammatory cytokines reached a significant level in either the comparison of CHR individuals and HC or between CHR-converters and non-converters. The C5, C3, D, I, and H levels were significantly lower (C5, p = 0.006; C3, p = 0.009; D, p = 0.026; I, p = 0.016; H, p = 0.019) in the CHR group than in the HC group. Compared to non-converters, converters had significantly lower levels of C5 (p = 0.012) and C5a (p = 0.007). None of the inflammatory factors, but many complement factors, showed significant correlations with changes in general function and symptoms. None of the inflammatory markers, except for C5a and C5, were significant in the discrimination of conversion outcomes in CHR individuals. Our results suggest that altered complement levels in the CHR population are more associated with conversion to psychosis than inflammatory factors. Therefore, an activated complement system may precede the first-episode of psychosis and contribute to neurological pathogenesis at the CHR stage.

Nodular Fasciitis of the Nose and External Auditory Canal: Two Rare Case Reports.

Nodular fasciitis(NF) is a proliferative disease of fibroblasts and myofibroblasts that generally affects subcutaneous tissue, muscle tissue, and fascia. NF usually occurs in young adults aged 20-40 and is more common in the upper extremities and relatively rare in the region of the head and neck. Here, we report on two patients with NF in the ear and nose. Under general anesthesia, the masses of NF were completely resected along the safety margin. The patients recovered well after surgery and there was no recurrence after more than half a year of follow-up.

Inhibition of alanine-serine-cysteine transporter 2-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between V-9302 and photosensitizer.

The efficiency of reactive oxygen species (ROS)-based photodynamic therapy (PDT) is far from satisfactory, because cancer cells can adapt to PDT by upregulating glutathione (GSH) levels. The GSH levels in tumor cells are determined based on glutamine availability via alanine-serine-cysteine transporter 2 (ASCT2)-mediated entry into cells. Herein, we develop co-assembled nanoparticles (PPa/V-9302 NPs) of the photosensitizer pyropheophorbide a (PPa) and V-9302 (a known inhibitor of ASCT2) in a 1:1 M ratio using a one-step precipitation method to auto-enhance photodynamic therapy. The computational simulations revealed that PPa and V-9302 could self-assemble through different driving forces, such as π-π stacking, hydrophobic interactions, and ionic bonds. Such PPa/V-9302 NPs could disrupt the intracellular redox homeostasis due to enhanced ROS production via PPa-induced PDT and reduced GSH synthesis via inhibition of the ASCT2-mediated glutamine flux by V-9302. The in vivo assays reveal that PPa/V-9302 NPs could increase the drug accumulation in tumor sites and suppress tumor growth in BALB/c mice bearing mouse breast carcinoma (4 T1) tumor. Our findings provide a new paradigm for the rational design of the PDT-based combinational cancer therapy.

Changes in inflammatory balance correlates with conversion to psychosis among individuals at clinical high-risk: A prospective cohort study.

Previous studies have revealed that the imbalance between Th1 cytokines and Th2 cytokines plays a role in disturbance of cellular responses in the brain during psychosis. Cross-sectional studies have implied that inflammatory cytokine changes emerge in early psychosis, even at the at-risk stage. This study aimed to test the hypothesis that inflammatory imbalance in clinical high-risk (CHR) individuals is associated with an increased risk of future psychosis. A prospective case-control study was performed to assess the Th1(interleukin (IL)-1ß)/Th2(IL-6) balance in 84 CHR individuals and 65 age- and sex-matched healthy controls (HC). Serum IL-1ß and IL-6 levels were measured by enzyme-linked immunosorbent assay at baseline and 1-year after the completion of the clinical assessment. Sixteen (19.0%) CHR participants converted to full psychosis during the 1-year follow-up period. At baseline, serum IL-1ß level was significantly lower in the CHR-converter group - resulting in decreased IL-1ß/IL-6 ratios - compared to those of the CHR-non-converter and HC groups. At the 1-year follow-up, IL-1ß level had decreased, and IL-1ß/IL-6 ratios had decreased in the CHR-non-converter group, such that these were comparable to values in the CHR-converter at this time point. Analysis of the changes in IL-1ß/IL-6 ratio between the baseline and 1-year follow-up measurements identified different trajectories in the CHR-converter and CHR-non-converter groups. Our findings demonstrate that a specific pattern of Th1/Th2 imbalance (decreased IL-1ß/IL-6 ratios with lower serum IL-1ß level) is associated with an increased risk of developing psychosis. Such specific pattern has potential for predicting conversion outcomes and selecting a distinct subgroup of CHR with immune-imbalanced-phenotype, that relevance in precise prevention.

GPX4-independent ferroptosis-a new strategy in disease's therapy.

Ferroptosis is a form of programmed cell death characterized by intracellular iron accumulation and lipid peroxidation, and earlier studies identified glutathione peroxidase 4 (GPX4) as an essential regulator of this process. Ferroptosis plays an essential role in tumors, degenerative diseases, and ischemia-reperfusion injury. However, researchers have found that inhibition of GPX4 does not entirely suppress ferroptosis in certain diseases, or cells express resistance to ferroptosis agonists that inhibit GPX4. As research progresses, it has been discovered that there are multiple regulatory pathways for ferroptosis that are independent of GPX4. The study of GPX4-independent ferroptosis pathways can better target ferroptosis to prevent and treat various diseases. Here, the currently inhibited pulmonary GPX4-dependent ferroptosis pathways will be reviewed.

Combination of resveratrol and luteolin ameliorates α-naphthylisothiocyanate-induced cholestasis by regulating the bile acid homeostasis and suppressing oxidative stress.

Cholestasis is a common liver injury without any effective therapeutic drugs so far. Resveratrol (RES) and luteolin (LUT) are natural polyphenols that exert protective effects on multiple liver injuries. Coadministration of RES and LUT could significantly improve the bioavailability of LUT and increase the systemic exposure to RES, and the combined treatment could also benefit from their multi-component and multi-target characteristics. Our current aim is to study the protective effects of coadministration of RES and LUT on α-naphthylisothiocyanate (ANIT)-induced cholestasis. Serum biochemical indices and liver histopathology in rats indicated that coadministration of RES and LUT could improve liver function by suppressing oxidative stress. Dysregulated bile acid (BA) homeostasis is a significant pathological feature of cholestasis, which was determined to explore the potential biomarkers and to clarify the protection mechanism of coadministration of RES and LUT. The levels of cholic acid, chenodeoxycholic acid, taurine conjugates and glycine conjugates, and the ratios of taurine conjugates to their free forms could be used as diagnosis indicators for cholestasis in rats. Furthermore, the coadministration of RES and LUT could restore the BA levels and exert better protective effects than administration alone. This study suggested that the coadministration of RES and LUT could protect against ANIT-induced cholestasis and the mechanism was closely related to regulating BA homeostasis and suppressing oxidative stress.

A rapid HPLC-MS/MS method for the simultaneous determination of luteolin, resveratrol and their metabolites in rat plasma and its application to pharmacokinetic interaction studies.

Both luteolin (LUT) and resveratrol (RES) are natural polyphenols that exert therapeutic effects on liver injuries. Extensive glucuronidation by uridine diphosphate-glucuronosyltransferases 1As (UGT1As) results in poor bioavailability of LUT, which limits its clinical application. As an inhibitor of UGT1A1 and UGT1A9, RES may affect the bioavailability of LUT. The purpose of this study was to develop and validate an HPLC-MS/MS method for the simultaneous determination of LUT, luteolin-3'-O-glucuronide (LUT-3'-G), RES and resveratrol-3-O-glucuronide (RES-3-G) in rat plasma to investigate the effects of RES on the bioavailability and metabolism of LUT after coadministration. The samples were extracted by protein precipitation with methanol using daidzein and naringenin as the internal standards. Separation was achieved on an XBridgeTM C18 column by isocratic elution using 88% methanol-12% water with 2 mM ammonium acetate and 0.01% formic acid. Multiple reaction monitoring mode with a negative electrospray ionization interface was used for quantification of the analytes. The calibration curves were linear over the concentration ranges of 1-1000 (r > 0.995), 2-2000 (r > 0.999), 5-5000 (r > 0.998) and 10-40000 ng/mL (r > 0.996) for LUT, LUT-3'-G, RES and RES-3-G, respectively. The method was fully validated in terms of accuracy, precision, matrix effect, recovery and stability. The validated data met the acceptance criteria in FDA guidelines. The method was successfully applied in a pharmacokinetic interaction study of LUT and RES. The results indicated that RES had a significant effect on the enhanced bioavailability of LUT by reducing the major glucuronidation metabolite in rats, which provides a reference for the combination of LUT and RES in liver diseases.

A Rare Case of Primary Neuroendocrine Carcinomas in the Ear and Throat and Review of Literatures.

The neuroendocrine carcinomas (NECs) of the head and neck are rare. The purpose of this article is to explore the diagnosis and treatment of NECs in the ear and larynx. We report a case of a patient with NECs found in the ear and throat simultaneously, and the relevant literatures are reviewed. It is difficult to identify which is the original site. There is no specific clinical manifestation of NECs in the ear and throat, and carcinoid syndrome is a rare situation. Surgery is still the preferred treatment for this disease. For patients with metastasis, radiotherapy and/or chemotherapy are required.