Objective: The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism. Methods: We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test. Results: Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness). Conclusion This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.

Objective: The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism. Methods: We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test. Results: Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness). Conclusion This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.

Objective: The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism. Methods: We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test. Results: Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness). Conclusion This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.

Objective: The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism. Methods: We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test. Results: Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness). Conclusion This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.

Objective: The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism. Methods: We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test. Results: Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness). Conclusion This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

OBJECTIVE: To explore the early clinical efficacy of a three-stage external treatment with traditional Chinese medicine (TCM) in the treatment of talar bone contusion caused by acute ankle sprain. METHODS: A retrospective analysis was performed on 360 patients with primary lateral ankle sprain admitted from September 2021 to July 2024. Patients with talar bone contusion were selected based on MRI examination, and 73 cases were finally included. According to different treatment methods, they were divided into the observation group and the control group. The observation group consisted of 35 cases, including 16 males and 19 females, aged 24 to 37 years old with an average of (30.34±2.68) years old, and received the three-stage external TCM treatment combined with the "POLICE" protocol. The control group included 38 cases, including 18 males and 20 females, aged 24 to 35 years old with an average of (29.87±2.57) years old, and was treated with the "POLICE" protocol alone. The volume of bone marrow edema (BME) area shown by MRI before treatment and 6 weeks after treatment was measured using 3D Slicer software, and the BME improvement rate was calculated. The "Figure of 8" measurement method was used to assess ankle swelling before treatment and at 1 and 3 weeks after treatment. The visual analogue scale (VAS) was used to evaluate ankle pain before treatment and at 1 and 6 weeks after treatment. At 6 weeks after treatment, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Karlsson ankle function score system were used to evaluate the improvement of ankle function. RESULTS: A total of 73 patients with talar bone contusion caused by ankle sprain completed the 6-week follow-up. At 6 weeks after treatment, the BME improvement rate in the observation group was (39.18±0.06)%, which was higher than (26.75±0.03)% in the control group, with a statistically significant difference (P<0.05). After 1 week of treatment, the VAS score in the observation group was (2.89±0.72) points, lower than (3.37±0.79) points in the control group, and the difference was statistically significant (P<0.05). The ankle swelling degree in the observation group was (50.20±3.19) cm, lower than (52.00±3.60) cm in the control group, with a statistically significant difference (P<0.05). After 3 weeks of treatment, there was no statistically significant difference in ankle swelling between the two groups. At 6 weeks after treatment, there was no statistically significant difference in VAS scores between the two groups. At 6 weeks after treatment, the AOFAS ankle-hindfoot score and Karlsson score in the observation group were (87.43±4.18) and (82.77±5.93) points, respectively, which were higher than (82.92±4.87) and (76.45±6.85) points in the control group, with statistically significant differences (P<0.05). According to the AOFAS ankle-hindfoot score, 8 cases were excellent and 27 cases were good in the observation group;2 cases were excellent, 33 cases were good, and 3 cases were fair in the control group. The difference between the two groups was statistically significant (χ²=7.089, P=0.029). CONCLUSION The three-stage external TCM treatment combined with the "POLICE" protocol has a significant early clinical efficacy. It can significantly reduce ankle pain and swelling in patients with bone contusion caused by acute lateral ankle sprain, promote the absorption of bone marrow edema, and accelerate the recovery of ankle function.
Ankle Injuries/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Talus/injuries* ; Retrospective Studies ; Administration, Cutaneous ; Magnetic Resonance Imaging ; Humans ; Male ; Female ; Young Adult ; Adult ; Contusions/etiology* ; Visual Analog Scale ; Musculoskeletal Pain/etiology* ; Recovery of Function/drug effects* ; Treatment Outcome ; Follow-Up Studies

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.