1.Sex Differences in Pain Contagion Determined by the Balance of Oxytocin and Corticosterone in the Anterior Cingulate Cortex in Rodents.
Zhiyuan XIE ; Wenxi YUAN ; Lingbo ZHOU ; Jie XIAO ; Huabao LIAO ; Jiang-Jian HU ; Xue-Jun SONG
Neuroscience Bulletin 2025;41(12):2167-2183
Empathy is crucial for communication and survival for individuals. Whether empathy in pain contagion shows sex differences and its underlying mechanisms remain unclear. Here, we report that pain contagion can occur in stranger female rats, but not in stranger males. Blocking oxytocin receptors in the anterior cingulate cortex (ACC) suppressed pain contagion in female strangers, while oxytocin administration induced pain contagion in male strangers. In vitro, corticosterone reduces neuronal activation by oxytocin. During male stranger interactions, higher corticosterone decreased oxytocin receptor-positive neuronal activity in the ACC, suppressing pain contagion. These findings highlight the role of oxytocin in pain contagion and suggest that sex differences in empathy may be determined by the balance of oxytocin and corticosterone in the ACC. This study suggests an approach for the treatment of certain mental disorders associated with abnormal empathy, such as autism and depression.
Animals
;
Oxytocin/pharmacology*
;
Gyrus Cinguli/drug effects*
;
Male
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Female
;
Corticosterone/pharmacology*
;
Empathy/drug effects*
;
Sex Characteristics
;
Receptors, Oxytocin/antagonists & inhibitors*
;
Pain/psychology*
;
Rats
;
Rats, Sprague-Dawley
;
Neurons/metabolism*
2.Effects of Split Formulas of Biyuan Heji on Paranasal Sinus Mucosal Inflammation in ARS Rats Based on the Pathogenesis of"Wind-Cold Transforming into Lung-Heat"
Huixia ZHOU ; Shanshan XUE ; Lu BAI ; Yang FANG ; Xinchen SUN ; Zhiyuan ZHU ; Yongjun WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(5):689-695
OBJECTIVE To investigate the effects of the split formulas of Biyuan Heji(BYHJ)on paranasal sinus mucosal in-flammation in rats with acute rhinosinusitis(ARS)based on the pathogenesis of"wind-cold transforming into lung-heat".METHODS Unilateral nasal cavity occlusion combined with nasal dripping of Staphylococcus aureus were performed to establish a rat model of ARS.SD rats were randomly divided into blank,model,BYHJ(wind-cold removal+lung-heat removal),lung-heat removal,wind-cold removal,and positive drug groups,with 6 rats in each group.The rats were treated with the corresponding drugs for 7 d and then the samples were collected.HE staining was used to observe the pathological changes of rat paranasal sinus mucosa tissues,ELISA was employed to determine the levels of interleukin-1β(IL-1β),IL-6,IL-8,IL-9,IL-10,and IL-12 in serum,immunohistochemis-try(IHC)was adopted to measure the protein expression of tumor necrosis factor-α(TNF-α)and intercellular adhesion molecule(ICAM-1)in paranasal sinus mucosa tissues,and Western blot was used to detect the protein expression of phosphorylated p38 mito-gen-activated protein kinase(p38 MAPK),nuclear transcription factor-κB p50(NF-κB p50),and NF-κB p65 in paranasal sinus mucosa tissues.RESULTS The acute sinusitis rat inflammation model was successfully established.Compared with the model group,the water drinking,diet eating,and body weight of rats in the BYHJ group,wind-cold removal,lung-heat removal,and positive drug groups were significantly improved,the aggregation of inflammatory cells in the paranasal sinus mucosal tissue was reduced,and the levels of IL-1β,IL-6,IL-8,IL-9,and IL-12 in the serum were significantly reduced(P<0.01),IL-10 content significantly in-creased(P<0.01),the protein expression of TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 in the paranasal sinus mucosa was significantly decreased(P<0.01).The comparison between various traditional Chinese medicine groups showed that the decrease of IL-1β,IL-6,IL-8,IL-9,IL-12,TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 and the increase of IL-10 in the BYHJ group were better than those in the split formula groups(P<0.01),and the lung-heat removal group was better than the wind-cold removal group(P<0.01).CONCLUSION BYHJ and its split formulas can effectively inhibit the inflammatory response in rats with ARS.
3.Nuclear translocation of NRF2 activates SLC7A11 and inhibits SAS-in-duced ferroptosis of AML cells
Yanfeng LIN ; Zhiyuan ZHENG ; Ying CHEN ; Wei WU ; Donghong LIN ; Yan XUE
Chinese Journal of Pathophysiology 2025;41(7):1289-1299
AIM:This study investigated the role of solute carrier family 7 member 11(SLC7A11)in sul-fasalazine(SAS)-induced ferroptosis in acute myeloid leukemia(AML)cells,focusing on the inhibitory effect of nuclear factor E2-related factor 2(NRF2)nuclear translocation-mediated activation of SLC7A11 on ferroptosis and its underlying mechanisms.METHODS:SAS-induced proliferation in AML cell lines,Kasumi-1 and THP-1,was assessed using the MTS assay.Cell death inhibitors were employed to determine the mode of cell death.Lipid reactive oxygen species(ROS)levels were measured by flow cytometry;Fe2+,malonodialdehyde(MDA),glutathione(GSH)levels,and glutathione per-oxidase 4(GPX4)activity were assessed using micromethods.Quantitative PCR(qPCR)was performed to evaluate changes in SLC7A11 mRNA during SAS-induced ferroptosis,while Western blot measured SLC7A11 and GPX4 protein levels.Moreover,Western blot assessed NRF2 nuclear translocation post-SAS treatment.The NRF2 inhibitor ML385 was used to validate these effects.SLC7A11 mRNA and protein levels were then measured following combined SAS and ML385 treatment via qPCR and Western blot.Cell viability and ferroptosis-related indices were evaluated under the same treatment conditions.Furthermore,a shRNA vector targeting SLC7A11 was constructed to assess changes in cell viability and ferroptosis markers after SLC7A11 knockdown with SAS.GPX4 protein levels were examined following SLC7A11 knockdown.RESULTS:SAS significantly inhibited the proliferation of Kasumi-1 and THP-1 cells at 200 μmol/L and 300 μmol/L,respectively(P<0.05).Only ferroptosis inhibitors(Fer-1 and DFO)significantly reversed SAS-induced cy-totoxicity(P<0.01).SAS increased lipid ROS,Fe2+,and MDA levels(P<0.01),while reducing GSH and GPX4 activity(P<0.01).The mRNA and protein expressions of SLC7A11 increased during SAS-induced ferroptosis(P<0.01),where-as GPX4 protein decreased significantly(P<0.01).SAS significantly increased the nuclear-to-cytoplasmic NRF2 ratio(P<0.01),which decreased upon co-treatment with ML385(P<0.05).Following SAS and ML385 co-treatment,both SLC7A11 mRNA and protein levels were downregulated(P<0.01).This combination treatment further reduced AML cell viability(P<0.01),an effect reversed by Fer-1 and DFO(P<0.01).Compared with SAS alone,the combination of SAS and ML385 significantly increased lipid ROS,Fe2+,and MDA while reducing GSH levels and GPX4 activity(P<0.01).SLC7A11 knockdown was successfully achieved.Compared with the NC shRNA group,SLC7A11 knockdown cells showed significantly decreased viability after SAS treatment,which was reversed by Fer-1 and DFO(P<0.01).Lipid ROS,Fe2+,and MDA content were significantly increased(P<0.01),and GSH and GPX4 were substantially decreased(P<0.05).Moreover,GPX4 protein expression was considerably reduced after SLC7A11 knockdown(P<0.01).CONCLUSION:SAS induces ferroptosis in AML cells.It promotes the nuclear translocation of NRF2 protein,which activates SLC7A11 ex-pression.Inhibition of NRF2 or downregulation of SLC7A11 sensitizes AML cells to SAS-induced ferroptosis.
4.Clinical Study on the Classic Prescription Xinyi Powder in Treating Allergic Rhinitis with Lung Deficiency Related Cold
Shanshan XUE ; Bingruo ZHENG ; Xinchen SUN ; Rongjin LU ; Zhiyuan ZHU ; Yongjun WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(2):257-262
OBJECTIVE To explore the clinical efficacy and possible mechanism of the classic prescription Xinyi Powder in the treatment of allergic rhinitis with lung deficiency related cold.METHODS A total of 189 patients who met the inclusion criteria of al-lergic rhinitis with lung deficiency related cold in the otolaryngology clinic of Jiangsu Province Hospital of Chinese Medicine from Janu-ary 2023 to July 2024 were selected and randomly divided into the experimental group(n=126)and the control group(n=63).The control group was treated with oral loratadine,and the experimental group took Xinyi Powder.Before and after treatment,the TNSS,TNNSS scores and TCM syndrome scores of the two groups of patients were compared to comprehensively evaluate the clinical efficacy.The changes in the patients'quality of life were evaluated in multiple dimensions using nasal VAS and RQLQ scores.The changes in serum IL-4,IL-5,IgE,SP and CGRP expression levels were detected by ELISA.RESULTS After 14 days of treatment,the TNSS,TNNSS,VAS,RQLQ scores and TCM syndrome scores of the two groups of patients were reduced(P<0.01);the experi-mental group was better than the control group in improving the concomitant symptoms such as nasal congestion,runny nose,postnasal drip,and itchy eyes(P<0.05,P<0.01),and it could also significantly improve the symptoms of fear of wind and cold,spontaneous sweating,shortness of breath,and cough with thin sputum(P<0.01),and the total RQLQ score was significantly better than the con-trol group(P<0.01).After treatment,the serum IL-4,IL-5,IgE,SP,and CGRP levels of the two groups of patients were signifi-cantly reduced(P<0.01),and there was no statistical difference between the two groups.CONCLUSION Xinyi Powder can signifi-cantly alleviate the nasal symptoms and systemic concomitant symptoms of patients with allergic rhinitis of lung deficiency and cold type,and significantly improve the quality of life of patients.It may play a therapeutic role by inhibiting the expression of inflammatory factors and neuropeptides and regulating neuroimmunity.
5.A Case of Severe Drug-induced Liver Injury and Systemic Rash Caused by Diclofenac Sodium Sustained-release Tablets Combined with Paishi Granules
Mengya JIN ; Ying GONG ; Yuanyuan GU ; Yanli ZHANG ; Tiantian LIU ; Xue ZHAO ; Wenya LIU ; Zhiyuan LI
Herald of Medicine 2025;44(10):1681-1683
One patient with kidney stones was prescribed Paishi granules and diclofenac sodium sustained-release tablets for pain relief in the outpatient setting.That evening,the patient took 1 sachet of Paishi granules and 1 diclofenac sodium sustained-release tablet together.The patient subsequently developed a generalized rash with itching.Liver function indexes of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(T-BiL),direct bilirubin(D-BiL),and alkaline phosphatase(ALP)were all 2 to 6 times higher than the upper limit of normal.After symptomatico treatment,the patients systemic rash had subsided,and the liver function indicators have returned to normal.
6.Effects of Split Formulas of Biyuan Heji on Paranasal Sinus Mucosal Inflammation in ARS Rats Based on the Pathogenesis of"Wind-Cold Transforming into Lung-Heat"
Huixia ZHOU ; Shanshan XUE ; Lu BAI ; Yang FANG ; Xinchen SUN ; Zhiyuan ZHU ; Yongjun WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(5):689-695
OBJECTIVE To investigate the effects of the split formulas of Biyuan Heji(BYHJ)on paranasal sinus mucosal in-flammation in rats with acute rhinosinusitis(ARS)based on the pathogenesis of"wind-cold transforming into lung-heat".METHODS Unilateral nasal cavity occlusion combined with nasal dripping of Staphylococcus aureus were performed to establish a rat model of ARS.SD rats were randomly divided into blank,model,BYHJ(wind-cold removal+lung-heat removal),lung-heat removal,wind-cold removal,and positive drug groups,with 6 rats in each group.The rats were treated with the corresponding drugs for 7 d and then the samples were collected.HE staining was used to observe the pathological changes of rat paranasal sinus mucosa tissues,ELISA was employed to determine the levels of interleukin-1β(IL-1β),IL-6,IL-8,IL-9,IL-10,and IL-12 in serum,immunohistochemis-try(IHC)was adopted to measure the protein expression of tumor necrosis factor-α(TNF-α)and intercellular adhesion molecule(ICAM-1)in paranasal sinus mucosa tissues,and Western blot was used to detect the protein expression of phosphorylated p38 mito-gen-activated protein kinase(p38 MAPK),nuclear transcription factor-κB p50(NF-κB p50),and NF-κB p65 in paranasal sinus mucosa tissues.RESULTS The acute sinusitis rat inflammation model was successfully established.Compared with the model group,the water drinking,diet eating,and body weight of rats in the BYHJ group,wind-cold removal,lung-heat removal,and positive drug groups were significantly improved,the aggregation of inflammatory cells in the paranasal sinus mucosal tissue was reduced,and the levels of IL-1β,IL-6,IL-8,IL-9,and IL-12 in the serum were significantly reduced(P<0.01),IL-10 content significantly in-creased(P<0.01),the protein expression of TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 in the paranasal sinus mucosa was significantly decreased(P<0.01).The comparison between various traditional Chinese medicine groups showed that the decrease of IL-1β,IL-6,IL-8,IL-9,IL-12,TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 and the increase of IL-10 in the BYHJ group were better than those in the split formula groups(P<0.01),and the lung-heat removal group was better than the wind-cold removal group(P<0.01).CONCLUSION BYHJ and its split formulas can effectively inhibit the inflammatory response in rats with ARS.
7.Nuclear translocation of NRF2 activates SLC7A11 and inhibits SAS-in-duced ferroptosis of AML cells
Yanfeng LIN ; Zhiyuan ZHENG ; Ying CHEN ; Wei WU ; Donghong LIN ; Yan XUE
Chinese Journal of Pathophysiology 2025;41(7):1289-1299
AIM:This study investigated the role of solute carrier family 7 member 11(SLC7A11)in sul-fasalazine(SAS)-induced ferroptosis in acute myeloid leukemia(AML)cells,focusing on the inhibitory effect of nuclear factor E2-related factor 2(NRF2)nuclear translocation-mediated activation of SLC7A11 on ferroptosis and its underlying mechanisms.METHODS:SAS-induced proliferation in AML cell lines,Kasumi-1 and THP-1,was assessed using the MTS assay.Cell death inhibitors were employed to determine the mode of cell death.Lipid reactive oxygen species(ROS)levels were measured by flow cytometry;Fe2+,malonodialdehyde(MDA),glutathione(GSH)levels,and glutathione per-oxidase 4(GPX4)activity were assessed using micromethods.Quantitative PCR(qPCR)was performed to evaluate changes in SLC7A11 mRNA during SAS-induced ferroptosis,while Western blot measured SLC7A11 and GPX4 protein levels.Moreover,Western blot assessed NRF2 nuclear translocation post-SAS treatment.The NRF2 inhibitor ML385 was used to validate these effects.SLC7A11 mRNA and protein levels were then measured following combined SAS and ML385 treatment via qPCR and Western blot.Cell viability and ferroptosis-related indices were evaluated under the same treatment conditions.Furthermore,a shRNA vector targeting SLC7A11 was constructed to assess changes in cell viability and ferroptosis markers after SLC7A11 knockdown with SAS.GPX4 protein levels were examined following SLC7A11 knockdown.RESULTS:SAS significantly inhibited the proliferation of Kasumi-1 and THP-1 cells at 200 μmol/L and 300 μmol/L,respectively(P<0.05).Only ferroptosis inhibitors(Fer-1 and DFO)significantly reversed SAS-induced cy-totoxicity(P<0.01).SAS increased lipid ROS,Fe2+,and MDA levels(P<0.01),while reducing GSH and GPX4 activity(P<0.01).The mRNA and protein expressions of SLC7A11 increased during SAS-induced ferroptosis(P<0.01),where-as GPX4 protein decreased significantly(P<0.01).SAS significantly increased the nuclear-to-cytoplasmic NRF2 ratio(P<0.01),which decreased upon co-treatment with ML385(P<0.05).Following SAS and ML385 co-treatment,both SLC7A11 mRNA and protein levels were downregulated(P<0.01).This combination treatment further reduced AML cell viability(P<0.01),an effect reversed by Fer-1 and DFO(P<0.01).Compared with SAS alone,the combination of SAS and ML385 significantly increased lipid ROS,Fe2+,and MDA while reducing GSH levels and GPX4 activity(P<0.01).SLC7A11 knockdown was successfully achieved.Compared with the NC shRNA group,SLC7A11 knockdown cells showed significantly decreased viability after SAS treatment,which was reversed by Fer-1 and DFO(P<0.01).Lipid ROS,Fe2+,and MDA content were significantly increased(P<0.01),and GSH and GPX4 were substantially decreased(P<0.05).Moreover,GPX4 protein expression was considerably reduced after SLC7A11 knockdown(P<0.01).CONCLUSION:SAS induces ferroptosis in AML cells.It promotes the nuclear translocation of NRF2 protein,which activates SLC7A11 ex-pression.Inhibition of NRF2 or downregulation of SLC7A11 sensitizes AML cells to SAS-induced ferroptosis.
8.Clinical Study on the Classic Prescription Xinyi Powder in Treating Allergic Rhinitis with Lung Deficiency Related Cold
Shanshan XUE ; Bingruo ZHENG ; Xinchen SUN ; Rongjin LU ; Zhiyuan ZHU ; Yongjun WU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(2):257-262
OBJECTIVE To explore the clinical efficacy and possible mechanism of the classic prescription Xinyi Powder in the treatment of allergic rhinitis with lung deficiency related cold.METHODS A total of 189 patients who met the inclusion criteria of al-lergic rhinitis with lung deficiency related cold in the otolaryngology clinic of Jiangsu Province Hospital of Chinese Medicine from Janu-ary 2023 to July 2024 were selected and randomly divided into the experimental group(n=126)and the control group(n=63).The control group was treated with oral loratadine,and the experimental group took Xinyi Powder.Before and after treatment,the TNSS,TNNSS scores and TCM syndrome scores of the two groups of patients were compared to comprehensively evaluate the clinical efficacy.The changes in the patients'quality of life were evaluated in multiple dimensions using nasal VAS and RQLQ scores.The changes in serum IL-4,IL-5,IgE,SP and CGRP expression levels were detected by ELISA.RESULTS After 14 days of treatment,the TNSS,TNNSS,VAS,RQLQ scores and TCM syndrome scores of the two groups of patients were reduced(P<0.01);the experi-mental group was better than the control group in improving the concomitant symptoms such as nasal congestion,runny nose,postnasal drip,and itchy eyes(P<0.05,P<0.01),and it could also significantly improve the symptoms of fear of wind and cold,spontaneous sweating,shortness of breath,and cough with thin sputum(P<0.01),and the total RQLQ score was significantly better than the con-trol group(P<0.01).After treatment,the serum IL-4,IL-5,IgE,SP,and CGRP levels of the two groups of patients were signifi-cantly reduced(P<0.01),and there was no statistical difference between the two groups.CONCLUSION Xinyi Powder can signifi-cantly alleviate the nasal symptoms and systemic concomitant symptoms of patients with allergic rhinitis of lung deficiency and cold type,and significantly improve the quality of life of patients.It may play a therapeutic role by inhibiting the expression of inflammatory factors and neuropeptides and regulating neuroimmunity.
9.A Case of Severe Drug-induced Liver Injury and Systemic Rash Caused by Diclofenac Sodium Sustained-release Tablets Combined with Paishi Granules
Mengya JIN ; Ying GONG ; Yuanyuan GU ; Yanli ZHANG ; Tiantian LIU ; Xue ZHAO ; Wenya LIU ; Zhiyuan LI
Herald of Medicine 2025;44(10):1681-1683
One patient with kidney stones was prescribed Paishi granules and diclofenac sodium sustained-release tablets for pain relief in the outpatient setting.That evening,the patient took 1 sachet of Paishi granules and 1 diclofenac sodium sustained-release tablet together.The patient subsequently developed a generalized rash with itching.Liver function indexes of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(T-BiL),direct bilirubin(D-BiL),and alkaline phosphatase(ALP)were all 2 to 6 times higher than the upper limit of normal.After symptomatico treatment,the patients systemic rash had subsided,and the liver function indicators have returned to normal.
10.Association between internal pentachlorophenol exposure characteristics and thyroid hormone indices in a community population in Shanghai, China
Yajiao TAN ; Zhiyuan DU ; Jiefeng QIAN ; Lingyi LU ; Xue BAI ; Zhou LI ; Weiwei ZHENG ; Sifei SUN ; Lanxia LIU
Shanghai Journal of Preventive Medicine 2024;36(8):746-752
ObjectiveTo assess the level of internal exposure to PCP in a community population in Shanghai, to investigate the factors affecting the level of PCP, and to analyze the correlation between the exposure and thyroid hormone levels. MethodsA total of 464 residents of a community in Shanghai were selected as the study subjects. A questionnaire survey was conducted to obtain the demographic information, dietary situation, lifestyle and behavioral habits, and disease history of the individuals, and blood samples were collected. Gas chromatography-electron trap was applied to determine the PCP levels in serum. Multicategorical logistic regression analysis was used to analyze the possible influencing factors of PCP exposure in humans. Thyroid hormone levels were used as the dependent variable and serum PCP as the independent variable. Multiple linear regression analysis was used to assess the association between PCP and thyroid hormones in the community population after controlling the confounding factors such as age, gender, literacy, annual personal income, and chronic diseases. ResultsThe detection rate of serum PCP in 464 subjects was 90.3%, and the median serum PCP level was 0.43 μg·L-1. The differences in PCP levels among different age groups were statistically significant. There were no significant differences in PCP levels among different gender and BMI groups. The study of PCP exposure factors showed that age, frequency of using plastic products, consumption of freshwater fish, type of occupation, annual income, and consumption of tea or coffee were the potential influencing factors for PCP exposure. Among them, age, frequency of using plastic products, consumption of tea or coffee, and consumption of freshwater fish were positively associated with PCP levels, and annual personal income was negatively associated with it. The results of multiple linear regression analysis showed that among men, PCP levels were positively correlated with TSH (b=0.105, 95%CI:0.017‒0.313) and negatively correlated with FT4 (b=-0.026, 95%CI:-0.057‒0.004), and among women, PCP levels were positively correlated with TSH (b=0.092, 95%CI:-0.211‒0.904) and FT3 (b=0.017, 95%CI:-0.058‒0.230) and negatively correlated with FT4 (b=-0.013, 95%CI:-0.011‒0.037). ConclusionSerum PCP detection is common among community residents in Shanghai. Different demographic characteristics or behavioral habits may increase or decrease PCP exposure. PCP exposure then affects human thyroid hormone levels.

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