Stress granules are highly dynamic, membrane-free organelles that form in cells under stress conditions through liquid-liquid phase separation.Their main components are RNA and proteins, and they play a role in RNA metabolism, among other functions.The formation, dispersion, and removal of stress granules are regulated by the rapamycin pathway, the eukaryotic translation initiation factor pathway, and modifications of RNA-binding proteins.While physiological stress granules are typically transient, chronic stress associated with aging can lead to homeostatic imbalance and persistence of these granules.This aberrant RNA metabolism can result in the pathological aggregation of RNA-binding proteins, cellular damage, and the formation of pathological stress granules, which may accelerate the progression of aging-related diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and tumors.In this paper, we will summarize the connection between stress granules and aging-related diseases to provide new insights for disease diagnosis and research.

Objective To observe the clinical efficacy of oral use combined with targeted transdermal delivery of Osteoking in treating knee osteoarthritis(KOA)of cold-damp blockage type.Methods A total of 120 patients with KOA of cold-damp blockage type who admitted to Hunan Provincial Hospital of Integrated Traditional Chinese And West Medicine from September 2022 to September 2023 were randomly divided into the control group,oral use group,transdermal delivery group and combination group according to the random number table method,with 30 cases in each group.The control group was treated with Celecoxib Capsule orally,the oral use group was treated with Osteoking orally,the transdermal delivery group was treated with Osteoking by targeted transdermal delivery,and the combination group was treated with oral use combined with targeted transdermal delivery of Osteoking.One course of treatment covered 12 days,and all of the four groups were treated for two continuous courses.Before and after treatment,the scores of traditional Chinese medicine(TCM)syndrome,Visual Analogue Scale(VAS)for pain,Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)for joint function,36-Item Short Form Health Survey(SF-36)for quality of life(QOL),as well as the levels of serum interleukin 1β(IL-1β),interleukin 6(IL-6),and tumor necrosis factor α(TNF-α)were observed in the patients of each group.After treatment,the clinical efficacy and safety of patients in each group were evaluated.Results(1)After two courses of treatment,the total effective rate of the combination group was 96.67%(29/30),which was higher than those of the control group[73.33%(22/30)],oral use group and transdermal delivery group[both being 70.00%(21/30)],and the difference was statistically significant(P<0.05).However,no statistically significant difference of the total effective rate was presented among the control group,oral use group,and transdermal delivery group(P>0.05).(2)After treatment,the scores of TCM syndrome,VAS for pain and WOMAC for joint function in the four groups were decreased compared with those before treatment(P<0.01).The intergroup comparison showed that the scores of TCM syndrome,VAS for pain and WOMAC in the combination group were lower than those in the other three groups(P<0.05),while no statistically significant difference of the scores of TCM syndrome,VAS for pain and WOMAC were presented among the control group,oral use group,and transdermal delivery group(P>0.05).(3)After treatment,the QOL scores of the eight dimensions of SF-36 such as physical functioning(PF),bodily pain(BP),general health(GH),vitality(VT),role-physical(RP),social functioning(SF),role-emotional(RE),and mental health(MH)in the four groups were significantly increased compared with those before treatment(P<0.01).The intergroup comparison showed that the scores of each dimension of SF-36 in the combination group were significantly higher than those in the other three groups(P<0.05),while no statistically significant difference of the dimension score of SF-36 was presented among the control group,oral use group,and transdermal delivery group(P>0.05).(4)After treatment,the levels of serum inflammatory factors of IL-1β,IL-6,and TNF-α in the four groups were decreased compared with those before treatment(P<0.01).The intergroup comparison showed that the decrease of serum levels of inflammatory factors in the combination group were significantly superior to those in the other three groups(P<0.05),and the decrease in the control group and oral use group were all superior to those in the transdermal delivery group(P<0.05),while the difference between the control group and oral use group was not statistically significant(P>0.05).(5)During the trial,no serious adverse reactions were found in the patients of four groups,which is of high safety.Conclusion Oral use combined with targeted transdermal delivery of Osteoking is effective on improving the joint pain,joint function and QOL of patients with KOA of cold-damp blockage type,and can speed up the rehabilitation of patients.Its therapeutic mechanism may be related to the decrease of the expression level of inflammatory factors.

Major depressive disorder in adolescents is a serious psychiatric condition characterized by profound impairment in psychosocial functioning. Its primary symptoms include low mood, irritability, and anhedonia. Although pharmacological treatments and psychotherapy are currently recommended as first-line treatments, their effectiveness is limited, and pharmacological treatments may carry the risk of increased suicidal ideation. Therefore, exploring new, effective, and safe treatment options is an urgent priority. In recent years, intermittent theta burst stimulation (iTBS), a novel form of transcranial magnetic stimulation, has shown promising results in treating treatment-resistant depression in adults, drawing growing interest in its potential use in adolescents. iTBS modulates neural activity through magnetic stimulation of the cerebral cortex and has been shown to alleviate depressive symptoms, particularly when targeting the left dorsolateral prefrontal cortex (DLPFC). Given the high neuroplasticity of the adolescent brain during this critical developmental stage, adolescents may exhibit heightened sensitivity to iTBS, resulting in more enduring neuroregulatory effects. Research highlights the importance of precise targeting and individualized adjustment of stimulation intensity for optimal therapeutic outcomes. Additionally, accelerated iTBS (aiTBS) protocols have demonstrated faster clinical effects in treating acute or severe depression in adolescents, improving treatment adherence and partially mitigating suicidal tendencies. This review summarizes recent progress in the application of iTBS in adolescent depression, with a focus on its mechanisms, treatment parameters, and related research. The goal is to provide theoretical support and practical guidance for the clinical application of iTBS in adolescent depression care.

Stress granules are highly dynamic, membrane-free organelles that form in cells under stress conditions through liquid-liquid phase separation.Their main components are RNA and proteins, and they play a role in RNA metabolism, among other functions.The formation, dispersion, and removal of stress granules are regulated by the rapamycin pathway, the eukaryotic translation initiation factor pathway, and modifications of RNA-binding proteins.While physiological stress granules are typically transient, chronic stress associated with aging can lead to homeostatic imbalance and persistence of these granules.This aberrant RNA metabolism can result in the pathological aggregation of RNA-binding proteins, cellular damage, and the formation of pathological stress granules, which may accelerate the progression of aging-related diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and tumors.In this paper, we will summarize the connection between stress granules and aging-related diseases to provide new insights for disease diagnosis and research.

Major depressive disorder in adolescents is a serious psychiatric condition characterized by profound impairment in psychosocial functioning. Its primary symptoms include low mood, irritability, and anhedonia. Although pharmacological treatments and psychotherapy are currently recommended as first-line treatments, their effectiveness is limited, and pharmacological treatments may carry the risk of increased suicidal ideation. Therefore, exploring new, effective, and safe treatment options is an urgent priority. In recent years, intermittent theta burst stimulation (iTBS), a novel form of transcranial magnetic stimulation, has shown promising results in treating treatment-resistant depression in adults, drawing growing interest in its potential use in adolescents. iTBS modulates neural activity through magnetic stimulation of the cerebral cortex and has been shown to alleviate depressive symptoms, particularly when targeting the left dorsolateral prefrontal cortex (DLPFC). Given the high neuroplasticity of the adolescent brain during this critical developmental stage, adolescents may exhibit heightened sensitivity to iTBS, resulting in more enduring neuroregulatory effects. Research highlights the importance of precise targeting and individualized adjustment of stimulation intensity for optimal therapeutic outcomes. Additionally, accelerated iTBS (aiTBS) protocols have demonstrated faster clinical effects in treating acute or severe depression in adolescents, improving treatment adherence and partially mitigating suicidal tendencies. This review summarizes recent progress in the application of iTBS in adolescent depression, with a focus on its mechanisms, treatment parameters, and related research. The goal is to provide theoretical support and practical guidance for the clinical application of iTBS in adolescent depression care.

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg^-1·d^-1）， and celecoxib group （10.9 mg·kg^-1·d^-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Objective:The aim of this study was to explore the molecular mechanisms of sulforaphane in the treatment of autism spectrum disorders (ASD), identify metabolomic biomarkers associated with efficacy and construct efficacy prediction models.Methods:Forty children with ASD who were treated in Second Xiangya Hospital of Central South University and Guangzhou Huiai Hospital were recruited from August 2016 to May 2019. The patients were randomly allocated into sulforaphane treatment group ( n=26) and placebo group ( n=14). The OSU Autism Rating Scale-DSM-Ⅳ (OARS-4) was used to assess the change in clinical symptoms of children with ASD at baseline, week 4, week 8 and week 12 of treatment. A generalized linear mixed model was used to compare the differences in OARS-4 scale scores between groups and time. Plasma samples were collected from patients before and after treatment for untargeted metabolomic detection using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Differential metabolites were screened using ANOVA-component analysis, and metabolic pathway analysis was performed. Then, spearman correlation analysis was performed to find differential metabolites significantly associated with the efficacy of sulforaphane treatment, and finally Fisher′s discriminant analysis was used to screen for efficacy predictors. Result:After 12 weeks of treatment, the clinical symptoms improvement was significantly better in the sulforaphane group than in the placebo group ( F=14.11, P<0.001). There were differences in a total of 201 metabolites between the two groups, which were mainly significantly enriched in glycerophospholipid metabolism and primary bile acid biosynthesis pathways. Spearman′s correlation analysis showed that taurine, phosphatidylserine and lysophosphatidylserine were significantly positively associated with symptom changes in patients with ASD ( r=0.643, 0.401, 0.414, P<0.05 or 0.001), while lysophosphatidylethanolamine, sphingomyelin and triglyceride metabolites were significantly negatively associated with symptom changes ( r=-0.481--0.392, all P<0.05). Among them, sphingomyelin (d35∶1) and taurine entered the Fisher′s discriminant analysis model, which the accuracy of efficacy prediction was 84.6%(22/26). Conclusions:The molecular mechanism of sulforaphane in improving ASD related clinical symptoms may be related to cell membrane phospholipid metabolism. Sphingomyelin (d35∶1) and taurine may be possible predictors on the efficacy of sulforaphane in the treatment of ASD.

Objective:The aim of this study was to explore the molecular mechanisms of sulforaphane in the treatment of autism spectrum disorders (ASD), identify metabolomic biomarkers associated with efficacy and construct efficacy prediction models.Methods:Forty children with ASD who were treated in Second Xiangya Hospital of Central South University and Guangzhou Huiai Hospital were recruited from August 2016 to May 2019. The patients were randomly allocated into sulforaphane treatment group ( n=26) and placebo group ( n=14). The OSU Autism Rating Scale-DSM-Ⅳ (OARS-4) was used to assess the change in clinical symptoms of children with ASD at baseline, week 4, week 8 and week 12 of treatment. A generalized linear mixed model was used to compare the differences in OARS-4 scale scores between groups and time. Plasma samples were collected from patients before and after treatment for untargeted metabolomic detection using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Differential metabolites were screened using ANOVA-component analysis, and metabolic pathway analysis was performed. Then, spearman correlation analysis was performed to find differential metabolites significantly associated with the efficacy of sulforaphane treatment, and finally Fisher′s discriminant analysis was used to screen for efficacy predictors. Result:After 12 weeks of treatment, the clinical symptoms improvement was significantly better in the sulforaphane group than in the placebo group ( F=14.11, P<0.001). There were differences in a total of 201 metabolites between the two groups, which were mainly significantly enriched in glycerophospholipid metabolism and primary bile acid biosynthesis pathways. Spearman′s correlation analysis showed that taurine, phosphatidylserine and lysophosphatidylserine were significantly positively associated with symptom changes in patients with ASD ( r=0.643, 0.401, 0.414, P<0.05 or 0.001), while lysophosphatidylethanolamine, sphingomyelin and triglyceride metabolites were significantly negatively associated with symptom changes ( r=-0.481--0.392, all P<0.05). Among them, sphingomyelin (d35∶1) and taurine entered the Fisher′s discriminant analysis model, which the accuracy of efficacy prediction was 84.6%(22/26). Conclusions:The molecular mechanism of sulforaphane in improving ASD related clinical symptoms may be related to cell membrane phospholipid metabolism. Sphingomyelin (d35∶1) and taurine may be possible predictors on the efficacy of sulforaphane in the treatment of ASD.

Objective:This study aims to investigate the impact of individual and family factors on non-suicidal self-injury (NSSI) behaviors in adolescents with mood disorders.Methods:Adolescents with mood disorders were included according to the ICD-10 diagnostic criteria, while the NSSI behaviors were assessed according to the DSM-5. The patients were divided into mood disorders with ( n=147) and without NSSI group ( n=56). Healthy adolescents were included as the control group ( n=107). The General Information Questionnaire, the Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, the Emotion Regulation Difficulties Scale, the Childhood Trauma Questionnaire, and the Parenting Style Scale were assessed. The three groups were compared using the χ 2 test and the analysis of variance, while the difference between two groups was compared using the t-test. Multiple logistic regression was used to explore the influence of various factors on NSSI behaviors. Results:Patients in the mood disorder with NSSI group scored significantly higher on depression, difficulties in emotion regulation, emotional abuse, and parental control than those in the mood disorder without NSSI group and the healthy control group. The multiple logistic regression analysis revealed that NSSI behaviors were positively correlated with depression ( OR=1.407, P<0.001), emotional abuse ( OR=1.186, P=0.03), and maternal encourage autonomy ( OR=1.302, P=0.035), and negatively correlated with paternal encourage autonomy ( OR=0.805, P=0.038), maternal care ( OR=0.731, P=0.025), and adolescent′s age (OR=0.656, P<0.001); adolescent′s age ( OR=0.851, P=0.042), paternal age ( OR=0.891, P=0.049) and male gender ( OR=0.435, P=0.040) were negatively correlated with NSSI behaviors. Conclusions:Gender, age, depression level, emotion regulation ability, personality traits, and parenting style had significant effects on adolescents′ NSSI behaviors.

Objective:This study aims to investigate the impact of individual and family factors on non-suicidal self-injury (NSSI) behaviors in adolescents with mood disorders.Methods:Adolescents with mood disorders were included according to the ICD-10 diagnostic criteria, while the NSSI behaviors were assessed according to the DSM-5. The patients were divided into mood disorders with ( n=147) and without NSSI group ( n=56). Healthy adolescents were included as the control group ( n=107). The General Information Questionnaire, the Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, the Emotion Regulation Difficulties Scale, the Childhood Trauma Questionnaire, and the Parenting Style Scale were assessed. The three groups were compared using the χ 2 test and the analysis of variance, while the difference between two groups was compared using the t-test. Multiple logistic regression was used to explore the influence of various factors on NSSI behaviors. Results:Patients in the mood disorder with NSSI group scored significantly higher on depression, difficulties in emotion regulation, emotional abuse, and parental control than those in the mood disorder without NSSI group and the healthy control group. The multiple logistic regression analysis revealed that NSSI behaviors were positively correlated with depression ( OR=1.407, P<0.001), emotional abuse ( OR=1.186, P=0.03), and maternal encourage autonomy ( OR=1.302, P=0.035), and negatively correlated with paternal encourage autonomy ( OR=0.805, P=0.038), maternal care ( OR=0.731, P=0.025), and adolescent′s age (OR=0.656, P<0.001); adolescent′s age ( OR=0.851, P=0.042), paternal age ( OR=0.891, P=0.049) and male gender ( OR=0.435, P=0.040) were negatively correlated with NSSI behaviors. Conclusions:Gender, age, depression level, emotion regulation ability, personality traits, and parenting style had significant effects on adolescents′ NSSI behaviors.