OBJECTIVES: Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression. METHODS: Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression. RESULTS: Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania. CONCLUSIONS This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans ; Bipolar Disorder/drug therapy* ; Vortioxetine/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Valproic Acid/administration & dosage* ; Lurasidone Hydrochloride/administration & dosage* ; Prospective Studies ; Treatment Outcome ; Pilot Projects ; Drug Therapy, Combination ; Sulfides/therapeutic use* ; Antidepressive Agents/therapeutic use*

Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic (ANT) application and affect gene expression. In this study, we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate (GLY), two ANTs, and one anticoccidial drug (AD). A total of 260 Ross 308 broilers aged 1‍-‍40 d were divided into the following four groups of 65 birds each: control group, which was fed the main diet (MD), and three experimental groups, which were fed MD supplemented with GLY, GLY+ANTs (enrofloxacin and colistin methanesulfonate), and GLY+AD (ammonium maduramicin), respectively. The results showed that the addition of GLY, GLY+ANTs, and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance. In particular, genes related to inflammation and apoptosis (interleukin 6 (IL6), prostaglandin-endoperoxide synthase 2 (PTGS2), and caspase 6 (CASP6)) were downregulated by up to 99.1%, and those related to antioxidant protection (catalase (CAT), superoxide dismutase 1 (SOD1) and peroxiredoxin 6 (PRDX6)) by up to 98.6%, compared to controls. There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups, and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood. The changes revealed in gene expression and blood indices in response to GLY, ANTs, and AD provide insights into the possible mechanisms of action of these agents at the molecular level. Specifically, these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY, GLY+ANTs, and GLY+AD in broilers.
Animals ; Glyphosate ; Glycine/administration & dosage* ; Chickens/blood* ; Pancreas/metabolism* ; Anti-Bacterial Agents/pharmacology* ; Animal Feed ; Gene Expression/drug effects* ; Herbicides

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol abundant in green tea, has garnered significant attention for its diverse therapeutic applications, ranging from antioxidant and anti-inflammatory effects to potential anticancer properties. Despite its immense promise, the practical utilization of EGCG in therapeutic settings as a medication has been hampered by inherent limitations of this drug, including poor bioavailability, instability, and rapid degradation. This review comprehensively explores the current challenges associated with the application of EGCG and evaluates the potential of nanoparticle-based formulations in addressing these limitations. Nanoparticles, with their unique physicochemical properties, offer a platform for the enhanced stability, bioavailability, and targeted delivery of EGCG. Various nanoparticle strategies, including polymeric nanoparticle, micelle, lipid-based nanocarrier, metal nanoparticle, and silica nanoparticle, are currently employed to enhance EGCG stability and pharmacological activity. This review concludes that the particle sizes of most of these formulated nanocarriers fall within 300 nm and their encapsulation efficiency ranges from 51% to 97%. Notably, the pharmacological activities of EGCG-loaded nanoparticles, such as antioxidative, anti-inflammatory, anticancer, and antimicrobial effects, are significantly enhanced compared to those of free EGCG. By critically analyzing the existing literature and highlighting recent advancements, this article provides valuable insights into the promising prospects of nanoparticle-mediated EGCG formulations, paving the way for the development of more effective and clinically viable therapeutic strategies.
Animals ; Humans ; Anti-Inflammatory Agents/administration & dosage* ; Antineoplastic Agents/administration & dosage* ; Antioxidants/administration & dosage* ; Biological Availability ; Catechin/analogs & derivatives* ; Micelles ; Particle Size ; Nanoparticle Drug Delivery System/chemistry*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Head and neck tumors are one of the major diseases that threaten human health. Targeted chemotherapy is an important treatment for head and neck tumors. However, many anti-cancer drugs are difficult to reach effective concentrations in tumors and can cause damage to normal tissues. Therefore, the efficient delivery of anti-tumor drugs, improvement of their therapeutic effects, and reduction of their adverse effects on the whole body and locally are urgent issues in targeted drug research. Liposomes have been widely studied due to their unique characteristics, including amphiphilicity, biocompatibility, biodegradability, and low toxicity. This article outlines the current applications and prospects of liposome drug delivery systems in different treatment modalities for head and neck tumors in recent years, aiming to provide more options for the treatment of head and neck tumors.
Humans ; Liposomes ; Head and Neck Neoplasms/drug therapy* ; Drug Delivery Systems ; Antineoplastic Agents/administration & dosage*

Objective:This study aimed to evaluate the therapeutic effect of intratympanic injection of ganglioside in patients with refractory sudden deafness. Methods:A total of 120 patients with sudden deafness, aged 18-65 years, whose onset was within 11-42 days, failed to respond to conventional treatment, and had an average hearing threshold（500-4 000 Hz）>60 dB were selected. They were prospectively and randomly divided into a control group of 61 cases and an experimental group of 59 cases. The control group was treated according to the recommended protocol of the Chinese Medical Association（postauricular injection of methylprednisolone）, while the experimental group was treated with intratympanic injection of monosialotetrahexosylganglioside sodium+postauricular injection of methylprednisolone. Both groups were simultaneously administered oral ginkgo biloba extract and citicoline tablets. Hearing was re-examined two weeks after the completion of treatment, and the therapeutic effects of the two different treatment methods were compared and analyzed. Results:The effective rate was 29.51% in the control group and 54.24% in the experimental group（P<0.01）. The average hearing threshold improved by 11.57 dB HL in the control group and 22.50 dB HL in the experimental group（P<0.05）. Conclusion:The combination of postauricular injection of methylprednisolone and intratympanic injection of ganglioside is more effective than postauricular injection of methylprednisolone alone in the treatment of refractory sudden deafness. The earlier the treatment, the better the therapeutic effect.
Humans ; Middle Aged ; Hearing Loss, Sudden/drug therapy* ; Adult ; Prospective Studies ; Young Adult ; Aged ; Adolescent ; Male ; Female ; Injection, Intratympanic ; Gangliosides/administration & dosage* ; Methylprednisolone/therapeutic use* ; Treatment Outcome

Objective:This study aims to explore the clinical effectiveness of a novel treatment method for refractory laryngeal contact granuloma, involving CO2 laser excision with local pedicled mucosal flap transfer combined with type A botulinum toxin injection. Methods:A retrospective analysis was conducted on 18 patients with refractory laryngeal contact granuloma who visited Department of Otolaryngology Head and Neck Surgery, Nanjing Tongren Hospital, School of Medicine, Southeast University from January 2021 to June 2023. These patients underwent CO2 laser excision of the granuloma with local pedicled mucosal flap transfer combined with type A botulinum toxin injection. During follow-up, electronic laryngoscopy were performed at 1, 3, 6, and 12 months postoperatively, and local laryngeal mucosa, voice quality, and pharyngeal discomfort symptoms were evaluated. Results:Postoperative electronic laryngoscopy revealed the disappearance of granulomas in all 18 patients. Symptoms such as hoarseness, foreign body sensation in the throat, and cough were significantly improved. No complications were observed systemically or locally. No recurrence was observed during one-year follow-up. Conclusion:CO2 laser excision of granuloma with local pedicled mucosal flap transfer combined with type A botulinum toxin injection could eliminate the lesion, restore the integrity of the vocal fold lining, preserve the perichondrium, and provide a time window for mucosal flap recovery. This approach adheres to the principle of preserving normal mucosa, achieves a high cure rate, and is therefore worthy of widespread promotion and application in clinical practice.
Humans ; Retrospective Studies ; Surgical Flaps ; Botulinum Toxins, Type A/administration & dosage* ; Male ; Female ; Granuloma/therapy* ; Adult ; Middle Aged ; Granuloma, Laryngeal/therapy* ; Laryngeal Diseases/therapy* ; Lasers, Gas/therapeutic use* ; Laryngoscopy ; Laser Therapy ; Treatment Outcome

Upper airway allergic disease in children refers to chronic non-infectious inflammatory diseases of the upper airway caused by allergic inflammation. These diseases have high prevalences and great harm. Attentions should be paid to the treatment of these diseases. Oral antihistamines play an important role in the treatment of allergic diseases. However, there are many types of antihistamines. How to select appropriate antihistamines according to the age and characteristics of children to treat upper airway allergic diseases is a concern of pediatricians. Therefore, the Pediatric Otorhinolaryngology and Head and Neck Surgery Committee of the Chinese Association for the Promotion of Human Health Science and Technology organized relevant experts to form this consensus, in order to guide the use of oral antihistamines in children with upper airway allergic diseases.
Humans ; Child ; Histamine Antagonists/administration & dosage* ; Administration, Oral ; Consensus ; Hypersensitivity/drug therapy*

Objective:To evaluate the clinical efficacy of single-dose arterial infusion chemotherapy（using cisplatin+5-fluorouracil（5-FU）） as a preoperative treatment for locally advanced head and neck malignant tumors, and to reassess tumor burden and lesion extent to guide the development of individualized treatment strategies. Methods:A total of 23 patients with locally advanced head and neck malignant tumors underwent preoperative assessments to determine the extent of the tumor and TNM staging. Treatment options were discussed with the patients and their families. Patients with significant tumor burden and a strong preference for preserving organ function received single-dose arterial infusion chemotherapy, followed by the formulation of an individualized treatment plan. A catheter was inserted through the femoral artery and selectively cannulated into the tumor-supplying artery via the external carotid artery, allowing direct infusion of chemotherapy drugs into the tumor core. Four weeks post-procedure, tumor burden was re-evaluated, and postoperative TNM staging was confirmed, leading to the development of an individualized treatment plan. Results:Among the 23 patients with head and neck malignant tumors, 4 achieved a complete respones（tumor reduction>75%）, 17 achieved a partial response（tumor reduction>50%）. One patient with recurrent oropharyngeal cancer received chemotherapy combined with immunotherapy after the T stage was reduced through treatment. In 113patients with hypopharyngeal cancer and 7 with oropharyngeal cancer, the surgical approach was optimized following treatment. Tow patient with hypopharyngeal cancer showed a stable disease response（tumor reduction>25% or no new lesions）, and after further assessment, a total laryngectomy was deemed appropriate. Conclusion:Among 23 patients with arterial infusion chemotherapy, the T stage of the 21 patients with head and neck malignant tumors decreased, and the local tumor burden was significantly reduced. Additionally, changes were observed in the size, shape, and boundaries of the cervical lymph nodes relative to surrounding tissues.
Humans ; Head and Neck Neoplasms/drug therapy* ; Infusions, Intra-Arterial ; Cisplatin/administration & dosage* ; Fluorouracil/administration & dosage* ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage* ; Aged ; Adult ; Treatment Outcome ; Neoplasm Staging