1.Potassium channel Kv1.3 mediates neurodysfunction and neuroin-flammation after traumatic brain injury
Xingxing CHEN ; Zhengxun CHEN ; Die ZHANG ; Haopeng JIANG ; Jie TAO ; Lele TANG ; Yi YUAN
Chinese Journal of Pharmacology and Toxicology 2025;39(6):401-411
OBJECTIVE To investigate the effects of potassium channel Kv1.3knockout(Kv1.3 KO)on neurological dysfunction and neuroinflammation in C57BL/6 mice following traumatic brain injury(TBI).METHODS C57BL/6 mice and homozygous Kv1.3 KO C57BL/6 mice were subjected to the classic controlled cortical impact model to establish a TBI model.The experimental groups included the sham surgery group,C57BL/6 TBI model group(TBI group),and a Kv1.3 KO C57BL/6 TBI model group(TBI+Kv1.3 KO group).At 1,2,and 3 weeks post-modeling,real-time quantitative PCR was used to measure the mRNA expression levels of Kv1.3,interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and IL-10 in hippocampal tissues.At 1 and 3 weeks post-modeling,Western blotting was performed to detect Kv1.3 protein expressions in the hippocampus.At 3 weeks post-modeling,Western blotting was used to assess the protein levels of IL-1β,IL-6,TNF-α,and IL-10 in hippocampal tissues.Additionally,immunofluorescence was employed to quantify cells co-labeled with the microglial marker ionized calcium-binding adapter molecule 1(IBA1)and Kv1.3,IL-1β,or TNF-α in the hippocampus.Patch-clamp recordings were conducted to measure Kv1.3 channel currents in primary microglia at 3 weeks post-modeling.Neurological function was evaluated at 1 and 3 weeks post-modeling using the neurological severity score(NSS),pole climbing,and rotarod tests.Cognitive function was assessed at 3 weeks post-modeling via open field,Morris water maze,and Y-maze tests.RESULTS Compared with the sham group,the TBI group exhibited significantly elevated mRNA expression levels of Kv1.3 and IL-1β in the hippocampus at 1,2 and 3 weeks post-modeling,while IL-6 and IL-10 mRNA levels showed no significant changes.Notably,TNF-α mRNA expressions demonstrated a significant increase only at 2 and 3 weeks post-modeling.At 1 and 3 weeks post-modeling,Kv1.3 protein expres-sions in the hippocampus were significantly higher in the TBI group.At 3 weeks post-modeling,hippo-campal IL-1β and TNF-α protein levels were markedly increased in the TBI group,whereas IL-6 and IL-10 protein levels did not change significantly.Moreover,Kv1.3 current density in primary microglia was signifi-cantly enhanced in the TBI group at 3 weeks post-modeling.Immunofluorescence analysis revealed that the number of IBA1-positive microglia co-labeled with Kv1.3,IL-1β,or TNF-α in the hippocampus was significantly larger in the TBI group than in the sham group at 3 weeks post-modeling.Behaviorally,the TBI group exhibited significantly higher NSS scores,lower success rates in full turn attempts,and longer times taken to descend the pole at 1 and 3 weeks post-modeling compared with the sham group.At 3 weeks post-modeling,TBI mice also demonstrated reduced total movement distance in the open field,decreased time spent in the central zone,fewer platform crossings,less time in the target quadrant,and lower spontaneous alternation rates.In contrast,the TBI+Kv1.3 KO group showed signifi-cantly improved outcomes compared with the TBI group:lower NSS scores,higher success rates in full turns,and shorter time taken to descend the pole at 1 and 3 weeks post-modeling.At 3 weeks post-modeling,the TBI+Kv1.3 KO group displayed longer rotarod endurance,increased total movement dis-tance in the open field,more time spent in the central zone,higher platform crossings,greater target quadrant exploration time,and improved spontaneous alternation rates.Furthermore,at 1 and 3 weeks post-modeling,the TBI+Kv1.3 KO group exhibited significantly reduced mRNA expression levels of the inflammatory cytokines IL-1β and TNF-α in the hippocampus compared with the TBI group.CONCLU-SION Potassium channel Kv1.3 knockout mitigates neurological dysfunction and neuroinflammation in C57BL/6 mice following TBI.
2.Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex.
Yu-Die YANG ; Wen ZHONG ; Ming CHEN ; Qing-Chen TANG ; Yan LI ; Lu-Lu YAO ; Mei-Qi ZHOU ; Neng-Gui XU ; Shuai CUI
Journal of Integrative Medicine 2025;23(5):537-547
OBJECTIVE:
To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2).
METHODS:
The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.
RESULTS:
Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors.
CONCLUSION
EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture
;
Stress Disorders, Post-Traumatic/metabolism*
;
Animals
;
Lipocalin-2/metabolism*
;
Prefrontal Cortex/physiopathology*
;
Male
;
Mice
;
Neurons/physiology*
;
Disease Models, Animal
;
Fear
;
Behavior, Animal
;
Mice, Inbred C57BL
;
Neuroinflammatory Diseases/metabolism*
;
Anxiety/therapy*
;
Acupuncture Points
3.Effect of preoperative intestinal prehabilitation on the recovery of delayed postoperative ileus in sarcopenic gastric cancer patients
Jian-Jun WU ; Guo-Zhong YAO ; Chu-Ming ZHU ; Jiang YAN ; Yu SHEN ; Shai-Di TANG ; Die WU
Parenteral & Enteral Nutrition 2025;32(5):283-287,292
Objective:To evaluate the effects and underlying mechanisms of preoperative intestinal microbiota modulation on the recovery of prolonged postoperative ileus(PPOI)in gastric cancer patients with sarcopenia Methods:Skeletal muscle mass(SMM)was assessed using bioelectrical impedance analysis(BIA),and the skeletal muscle index(SMI)was calculated.A total of 156 gastric cancer patients with sarcopenia who underwent surgery at the Department of Gastrointestinal Surgery,Liyang People's Hospital,from January 2022 to December 2024 were randomly assigned to either the control group or the experimental group.The control group received conventional prehabilitation interventions,including nutritional support,respiratory function training,and physical exercise.The experimental group received probiotic-based intestinal microbiota modulation in addition to conventional prehabilitation interventions.Postoperative recovery indicators,including time to first flatus,incidence of postoperative complications,length of hospital stay,and hospitalization costs,were compared between the two groups.Results:Among the 156 sarcopenic gastric cancer patients,121 were male,and 35 were female.Statistically significant differences were observed between the two groups in terms of time to first flatus,incidence of postoperative complications,and length of hospital stay(P<0.05).Postoperative complications occurred in 38 patients(24.3%),with 10 cases(6.4%)in the experimental group and 28 cases(17.9%)in the control group.The time to first flatus in the experimental group was significantly shorter than in the control group(48.0 hours vs 72.0 hours,P<0.001).Conclusion:Preoperative intestinal microbiota modulation significantly reduces the incidence of PPOI and postoperative complications in gastric cancer patients with low SMI,thereby promoting postoperative gastrointestinal function recovery.
4.The regulatory role of Dendrobium nobile Lindl alkaloids on the proliferation,migration,and epithelial-mesenchymal transition of human lens epithelial cells induced by TGF-β2
Yinglan SHI ; Zhaoxia HUANG ; Xiaofang TANG ; Die SHI ; Jing CHEN ; Jun LI
The Journal of Practical Medicine 2025;41(20):3165-3174
Objective To investigate the regulatory effect of Dendrobium nobile Lindl alkaloids(DNLA)on the proliferation,migration,and epithelial-mesenchymal transition(EMT)of HLEB3 cells induced by TGF-β2.Methods HLEB3 cells were cultivated in vitro and classified into the control group(DZ),the model group(TGF-β2),and the treatment group(TGF-β2+DNLA).TGF-β2 induced the EMT process of HLEB3 cells.Changes in cell morphology were observed through an inverted microscope.Cell proliferation,apoptosis,and migration were detected by CCK-8 assay,scratch test,and Transwell assay.The total RNAs of the samples were extracted for transcriptome analysis.Bioinformatics processing was employed to obtain relevant information on gene expression differences at the transcriptional level,biological processes,and related signaling pathways.The Western blot(WB)technique was utilized to detect EMT-related proteins to elucidate the mechanism of action of DNLA on lens epithelial cells.Results The study revealed that 10 μg/ml DNLA was suitable for the growth of HLEB3 cells.After 48 hours of the scratch test,the migration rate of the TGF-β2+DNLA group significantly decreased(P<0.01).The Transwell results indicated that the cell migration ability of the TGF-β2+DNLA group was notably weakened(P<0.05).Through bioinformatics,it was discovered that the prevention and treatment of posterior capsular opacification(PCO)by DNLA might be associated with cell junctions,cytoskeleton construction,and fibronectin binding.The pathogenesis of PCO may be related to multiple signaling pathways,including the TGF-β signaling pathway,TNF signaling pathway,and PI3K-Akt signaling pathway.Simultaneously,DNLA could reduce the expression levels of FNI,Smad2/3,and α-SMA proteins and increase the expression of E-cadherin protein.This indicates that DNLA can alleviate abnormal proliferation,migration,and EMT of lens epithelial cells by enhancing intercellular adhesion junctions and weakening cell migration ability,thereby playing a role in preventing and treating posterior capsular opacification.Conclusions DNLA can significantly inhibit the abnormal proliferation and migration of HLEB3 cells,alleviate the EMT process induced by TGF-β2,and prevent and control the occurrence of posterior capsular opacification and other ocular diseases.The mechanism of action might be related to the intervention of the TGF-β/smad signaling pathway and fibrosis proteins such as ZO-1 and E-cadherin.
5.Design and application of a special bra for vest-type breast dressing
Dan LIU ; Lu ZHENG ; Shuhua YE ; Die TANG ; Li LUO ; Milin LAI ; Jingyan ZHANG
Chinese Journal of Practical Nursing 2025;41(13):987-992
Objective:To design a vest-type breast dressing bra and explore its application effect in the external application of traditional Chinese medicine therapy for patients with granulomatous lobular mastitis(GLM).Methods:A randomized controlled study was conducted, utilizing convenience sampling to select female patients with 122 GLM who underwent their first topical medication treatment in the Breast Department of Guangdong Provincial Hospital of Traditional Chinese Medicine between January and May 2023. The patients were divided into a control group and an observation group, with 61 patients in each, using a random number table. Following medication application, patients in the control group used a regular sports bra to secure the medication, while patients in the observation group used a custom-designed vest-style breast medication bra for the same purpose. Three hours after the intervention, comparisons were made between the two groups in terms of the incidence of medication detachment, medication displacement, clothing contamination, patient satisfaction, and safety.Results:Both groups of patients completed the study. The age of the observation group was (32.18 ± 5.50) years old, while the age of the control group was (33.66 ± 5.20) years old. Three hours after the intervention, the incidence of medication detachment, medication displacement, clothing contamination in the observation group were 3.28% (2/61), 6.56% (4/61), and 8.20% (5/61), which were lower than those in the control group with 18.03% (11/61), 26.23% (16/61), and 67.21% (41/61), respectively. The differences were statistically significant ( χ2=6.97, 8.61, 45.23; all P<0.05). The satisfaction level of patients towards the bra in the observation group was (4.43 ± 0.85) points, higher than that of the control group (3.85 ± 1.08) points, with a statistically significant difference ( t=3.30, P<0.05). The incidence rates of skin allergic reactions were 3.28%(2/61) and 4.92%(3/61) in the observation group and the control group, respectively, with no statistically significant difference ( P>0.05). Conclusions:The vest-type breast dressing bra designed in this study can properly secure the medicinal paste, reduce the rate of medication detachment, medication displacement, clothing contamination, and enhance patient satisfaction. It facilitates the external application of traditional Chinese medicine for patients with GLM and is worthy of clinical promotion.
6.Association of school bullying and psychological resilience with suicide attempts in children and adolescents with major depressive disorder
Kewen YAN ; Caiying ZHANG ; Ziyang HUANG ; Li XU ; Rushuang ZENG ; Die ZHANG ; Chengxia TANG ; Tong LI ; Yiling XIE ; Yaru CAO ; Linling JIANG ; Runxu YANG ; Yusan CHE ; Jin LU ; Yuanyuan XIAO
Chinese Mental Health Journal 2025;39(5):416-422
Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95%CI:1.14-3.02)and indirect bullying(OR=1.48,95%CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95%CI:0.45-0.85)and positive cognition(OR=0.62,95%CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.
7.Current status and influencing factors of self-disgust in female breast cancer patients
Dan LIU ; Shuhua YE ; Youyuan FU ; Die TANG ; Lifang XIANG ; Jiahua WU
Chinese Journal of Modern Nursing 2025;31(15):2053-2058
Objective:To explore the current status of self-disgust in female breast cancer patients and analyze its influencing factors, so as to provide reference for clinical intervention.Methods:Convenience sampling was used to select 283 female breast cancer patients who were hospitalized in Guangdong Provincial Hospital of Chinese Medicine from June to July 2024 for the study. A questionnaire survey was conducted using the General Information Questionnaire, Questionnaire for the Assessment of Self-Disgust (QASD), Family Avoidance of Communication about Cancer Scale, Body Image Scale, and the Chinese version of the Female Self-Advocacy in Cancer Survivorship. Factors influencing patients' self-disgust were analyzed using one-way analysis of variance and multiple linear regression.Results:The total score of QASD in female breast cancer patients was (33.77±7.64). Education level, sexual dysfunction after breast cancer, family avoidance of communication about cancer, body image and self-advocacy were influencing factors of self-disgust in female breast cancer patients ( P<0.05) . Conclusions:Self-disgust of female patients with breast cancer is at a medium to high level. It is recommended that nurses pay attention to the psychological status of patients with low level of education and sexual dysfunction after the disease, implement targeted psychological interventions to improve the family avoidance of communication about cancer and body image, and increase the awareness of self-advocacy, thus reducing the risk of self-disgust in female breast cancer patients.
8.The regulatory role of Dendrobium nobile Lindl alkaloids on the proliferation,migration,and epithelial-mesenchymal transition of human lens epithelial cells induced by TGF-β2
Yinglan SHI ; Zhaoxia HUANG ; Xiaofang TANG ; Die SHI ; Jing CHEN ; Jun LI
The Journal of Practical Medicine 2025;41(20):3165-3174
Objective To investigate the regulatory effect of Dendrobium nobile Lindl alkaloids(DNLA)on the proliferation,migration,and epithelial-mesenchymal transition(EMT)of HLEB3 cells induced by TGF-β2.Methods HLEB3 cells were cultivated in vitro and classified into the control group(DZ),the model group(TGF-β2),and the treatment group(TGF-β2+DNLA).TGF-β2 induced the EMT process of HLEB3 cells.Changes in cell morphology were observed through an inverted microscope.Cell proliferation,apoptosis,and migration were detected by CCK-8 assay,scratch test,and Transwell assay.The total RNAs of the samples were extracted for transcriptome analysis.Bioinformatics processing was employed to obtain relevant information on gene expression differences at the transcriptional level,biological processes,and related signaling pathways.The Western blot(WB)technique was utilized to detect EMT-related proteins to elucidate the mechanism of action of DNLA on lens epithelial cells.Results The study revealed that 10 μg/ml DNLA was suitable for the growth of HLEB3 cells.After 48 hours of the scratch test,the migration rate of the TGF-β2+DNLA group significantly decreased(P<0.01).The Transwell results indicated that the cell migration ability of the TGF-β2+DNLA group was notably weakened(P<0.05).Through bioinformatics,it was discovered that the prevention and treatment of posterior capsular opacification(PCO)by DNLA might be associated with cell junctions,cytoskeleton construction,and fibronectin binding.The pathogenesis of PCO may be related to multiple signaling pathways,including the TGF-β signaling pathway,TNF signaling pathway,and PI3K-Akt signaling pathway.Simultaneously,DNLA could reduce the expression levels of FNI,Smad2/3,and α-SMA proteins and increase the expression of E-cadherin protein.This indicates that DNLA can alleviate abnormal proliferation,migration,and EMT of lens epithelial cells by enhancing intercellular adhesion junctions and weakening cell migration ability,thereby playing a role in preventing and treating posterior capsular opacification.Conclusions DNLA can significantly inhibit the abnormal proliferation and migration of HLEB3 cells,alleviate the EMT process induced by TGF-β2,and prevent and control the occurrence of posterior capsular opacification and other ocular diseases.The mechanism of action might be related to the intervention of the TGF-β/smad signaling pathway and fibrosis proteins such as ZO-1 and E-cadherin.
9.Association of school bullying and psychological resilience with suicide attempts in children and adolescents with major depressive disorder
Kewen YAN ; Caiying ZHANG ; Ziyang HUANG ; Li XU ; Rushuang ZENG ; Die ZHANG ; Chengxia TANG ; Tong LI ; Yiling XIE ; Yaru CAO ; Linling JIANG ; Runxu YANG ; Yusan CHE ; Jin LU ; Yuanyuan XIAO
Chinese Mental Health Journal 2025;39(5):416-422
Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95%CI:1.14-3.02)and indirect bullying(OR=1.48,95%CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95%CI:0.45-0.85)and positive cognition(OR=0.62,95%CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.
10.Potassium channel Kv1.3 mediates neurodysfunction and neuroin-flammation after traumatic brain injury
Xingxing CHEN ; Zhengxun CHEN ; Die ZHANG ; Haopeng JIANG ; Jie TAO ; Lele TANG ; Yi YUAN
Chinese Journal of Pharmacology and Toxicology 2025;39(6):401-411
OBJECTIVE To investigate the effects of potassium channel Kv1.3knockout(Kv1.3 KO)on neurological dysfunction and neuroinflammation in C57BL/6 mice following traumatic brain injury(TBI).METHODS C57BL/6 mice and homozygous Kv1.3 KO C57BL/6 mice were subjected to the classic controlled cortical impact model to establish a TBI model.The experimental groups included the sham surgery group,C57BL/6 TBI model group(TBI group),and a Kv1.3 KO C57BL/6 TBI model group(TBI+Kv1.3 KO group).At 1,2,and 3 weeks post-modeling,real-time quantitative PCR was used to measure the mRNA expression levels of Kv1.3,interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and IL-10 in hippocampal tissues.At 1 and 3 weeks post-modeling,Western blotting was performed to detect Kv1.3 protein expressions in the hippocampus.At 3 weeks post-modeling,Western blotting was used to assess the protein levels of IL-1β,IL-6,TNF-α,and IL-10 in hippocampal tissues.Additionally,immunofluorescence was employed to quantify cells co-labeled with the microglial marker ionized calcium-binding adapter molecule 1(IBA1)and Kv1.3,IL-1β,or TNF-α in the hippocampus.Patch-clamp recordings were conducted to measure Kv1.3 channel currents in primary microglia at 3 weeks post-modeling.Neurological function was evaluated at 1 and 3 weeks post-modeling using the neurological severity score(NSS),pole climbing,and rotarod tests.Cognitive function was assessed at 3 weeks post-modeling via open field,Morris water maze,and Y-maze tests.RESULTS Compared with the sham group,the TBI group exhibited significantly elevated mRNA expression levels of Kv1.3 and IL-1β in the hippocampus at 1,2 and 3 weeks post-modeling,while IL-6 and IL-10 mRNA levels showed no significant changes.Notably,TNF-α mRNA expressions demonstrated a significant increase only at 2 and 3 weeks post-modeling.At 1 and 3 weeks post-modeling,Kv1.3 protein expres-sions in the hippocampus were significantly higher in the TBI group.At 3 weeks post-modeling,hippo-campal IL-1β and TNF-α protein levels were markedly increased in the TBI group,whereas IL-6 and IL-10 protein levels did not change significantly.Moreover,Kv1.3 current density in primary microglia was signifi-cantly enhanced in the TBI group at 3 weeks post-modeling.Immunofluorescence analysis revealed that the number of IBA1-positive microglia co-labeled with Kv1.3,IL-1β,or TNF-α in the hippocampus was significantly larger in the TBI group than in the sham group at 3 weeks post-modeling.Behaviorally,the TBI group exhibited significantly higher NSS scores,lower success rates in full turn attempts,and longer times taken to descend the pole at 1 and 3 weeks post-modeling compared with the sham group.At 3 weeks post-modeling,TBI mice also demonstrated reduced total movement distance in the open field,decreased time spent in the central zone,fewer platform crossings,less time in the target quadrant,and lower spontaneous alternation rates.In contrast,the TBI+Kv1.3 KO group showed signifi-cantly improved outcomes compared with the TBI group:lower NSS scores,higher success rates in full turns,and shorter time taken to descend the pole at 1 and 3 weeks post-modeling.At 3 weeks post-modeling,the TBI+Kv1.3 KO group displayed longer rotarod endurance,increased total movement dis-tance in the open field,more time spent in the central zone,higher platform crossings,greater target quadrant exploration time,and improved spontaneous alternation rates.Furthermore,at 1 and 3 weeks post-modeling,the TBI+Kv1.3 KO group exhibited significantly reduced mRNA expression levels of the inflammatory cytokines IL-1β and TNF-α in the hippocampus compared with the TBI group.CONCLU-SION Potassium channel Kv1.3 knockout mitigates neurological dysfunction and neuroinflammation in C57BL/6 mice following TBI.

Result Analysis
Print
Save
E-mail