1.Modified Xiehuangsan Regulates Microglial Polarization and TLR4/MyD88/NF-κB Pathway to Treat Tic Disorders in Rats
Mengjie ZHAO ; Qiong ZHAO ; Cuiling YANG ; Hongyun ZHOU ; Xiangjuan SUN ; Xinyi GUO ; Sajiyue HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):10-18
ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders (TD) based on microglial polarization and the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor (NF)-κB pathway. MethodsSeventy-two Sprague-Dawley (SD) rats were randomly assigned into six groups: control, model, tiapride (0.025 g·kg-1), and low-, medium-, and high-dose (12, 24, 48 g·kg-1, respectively) modified Xiehuangsan, with 12 rats in each group. Except the control group, the other groups received intraperitoneal injection of 3,3'-iminodipropionitrile (IDPN) for 7 consecutive days for the modeling of TD. After successful modeling, the control and model groups were given normal saline via gavage, and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention, rat behaviors were observed, and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-4, TLR4, MyD88, and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 (Iba1), Fc receptor family for immunoglobulin (Ig)G type Ⅲ (CD16), mannose receptor (CD206), TLR4, MyD88, and NF-κB p65 in the striatum. ResultsCompared with the control group, the model group showed increased stereotyped behaviors, locomotor activity, total movement distance, and movement speed, shortened resting time (P<0.01), and noticeable pathological changes in the striatum. Compared with the model group, the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior, locomotor activity, total movement distance, and movement speed, prolonged resting time (P<0.05, P<0.01), and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups, the high-dose group had the best intervention effect and the mildest pathological changes. Therefore, the high-dose group was selected for further research. Compared with the control group, the modeling of TD increased Iba1 and CD16 expression (P<0.05, P<0.01), up-regulated the mRNA levels of IL-1β and TNF-α (P<0.05, P<0.01), down-regulated the mRNA level of IL-4 (P<0.05), up-regulated the mRNA and protein levels of TLR4 and MyD88 (P<0.05, P<0.01), and up-regulated the protein level of NF-κB p65 (P<0.01). Compared with the model group, modified Xiehuangsan reduced Iba1 and CD16 expression (P<0.05, P<0.01), up-regulated the protein level of CD206 (P<0.05, P<0.01), down-regulated the mRNA levels of IL-1β and TNF-α (P<0.05), up-regulated the mRNA level of IL-4 (P<0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, and NF-κB p65 (P<0.05, P<0.01). ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.
2.Exploring the Traditional Chinese Medicine Diagnosis and Treatment of Psoriasis from the Perspective of Blood Turbidity Theory and Its Correlation with Oxidative Stress
Zeju DI ; Suqing YANG ; Qiong ZHANG ; Songyan WANG
Journal of Traditional Chinese Medicine 2025;66(7):690-694
Oxidative stress can activate multiple inflammatory pathways, triggering and exacerbating psoriasis lesions. In traditional Chinese medicine (TCM), blood turbidity refers to a pathological condition in which harmful stimuli or unhealthy lifestyle habits lead to an accumulation of impurities in the blood, resulting in increased viscosity and impaired circulation. Based on the correlation between blood turbidity theory in TCM and the pathological changes of oxidative stress in modern medicine, this paper explored the TCM diagnosis and treatment of psoriasis, proposing that spleen deficiency with latent turbidity is the fundamental cause of the disease. The pathological progression of psoriasis was outlined as follows, spleen deficiency with latent turbidity→phlegm and blood stasis intertwining→internal generation of toxic pathogens. Targeting oxidative stress, the study suggests syndrome differentiation and treatment with angle medicine (角药, means three medicinals combination). The treatment strategy divided into three stages. For early stage, strengthening the spleen and directing the turbid downward, emphasizing prevention before onset, with angle medicine of Huangqi (Astragali Radix) - Fuling (Poria) - Baizhu (Atractylodis macrocephalae rhizoma) to treat; for middle stage, resolving phlegm and dispersing blood stasis, preventing disease progression, if patient with more phlegm syndrome treated with angle medicine of Banxia (Pinelliae rhizoma) - Chenpi (Citri reticulatae pericarpium) - Zhexie (Alismatis rhizoma), and if patient with more stasis syndrome treated with Zicao (Arnebiae Radix) - Jixueteng (Spatholobi caulis) - Shouwuteng (Polygonum multiflorum Thunb); for late stage, resolving toxins and dispelling pathogens, balancing both attack and supplementation, with Quanxie (Scorpio) - Tufuling (Smilacis glabrae rhizoma) - Shudihuang (Rehmanniae radix praeparata) to treat.
3.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
4.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
5.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
6.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
7.Causal association of obesity and chronic pain mediated by educational attainment and smoking: a mediation Mendelian randomization study
Yunshu LYU ; Qingxing LU ; Yane LIU ; Mengtong XIE ; Lintong JIANG ; Junnan LI ; Ning WANG ; Xianglong DAI ; Yuqi YANG ; Peiming JIANG ; Qiong YU
The Korean Journal of Pain 2025;38(2):177-186
Background:
Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.
Methods:
This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.
Results:
The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.
Conclusions
The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.
8.Analysis of the incidence and relevant factors of visual acuity abnormalities in preschool children undergoing kindergarten entrance physical examinations in Shannan City, Xizang, 2022
Sangzhu LABA ; Zhuoma QIONG ; Fei YANG ; Zhuoga SUOLANG ; Ruiqi ZHANG ; Jun CHEN ; Hui YIN ; Hong ZHOU
Shanghai Journal of Preventive Medicine 2025;37(6):535-539
ObjectiveTo investigate the incidence and relevant factors of visual acuity abnormalities in preschool children undergoing kindergarten entrance physical examinations in Shannan City, Xizang, in 2022, so as to formulate policies for protecting children’s visual acuity and provide a basis for optimizing the children’s health service system in this region. MethodsA cross sectional study was conducted among the children undergoing kindergarten entrance physical examinations in Shannan City in 2022. A diopter examination was performed for these children, and a questionnaire survey was administered to their caregivers. Additionally, factors affecting children’s visual acuity abnormalities were analyzed using the χ² test and binary logistic regression analysis. ResultsA total of 759 children were included in the analysis, with an incidence rate for visual acuity abnormalities of 11.20%. Univariate analysis showed that statistically significant differences were observed in the incidence rate for visual acuity abnormalities among preschool children in terms of different family monthly income (χ²=17.395, P<0.001), father’s education level (χ²=5.133, P=0.023), postnatal vitamin A and D supplementation (χ²=9.575, P=0.008), and feeding method within the first 6 months after birth (χ²=9.330, P=0.009). Multivariate analysis results indicated that family monthly income <5 000 yuan (OR=2.599, P=0.003), insufficient postnatal vitamin A and D supplementation (OR=1.912, P=0.011), and formula feeding (OR=2.131, P=0.010) were relevant factors for abnormal visual development in children. ConclusionThe incidence of visual acuity abnormalities in preschool children in Shannan City is slightly higher than that previously reported in other regions of Xizang. The occurrence of visual acuity abnormalities in children is related to factors such as family monthly income, postnatal vitamin A and D supplementation, and feeding method within the first 6 months after birth. Future interventions should be strengthened on the promotion and dissemination of knowledge related to eye use, such as improve parental awareness of eye care, promote timely vitamin A and D supplementation and encourage breast feeding for children after birth, more specifically, attentions need to be focused on the visual acuity problems of children from low-income families to safeguard the visual health in preschool children in Shannan City, Xizang.
9.Clinical trial of dydrogesterone combined with granulocyte colony-stimulating factor in the treatment of patients with thin endometrial infertility
Qiong ZHOU ; Wei-Hui YANG ; Xiao-Hong LU ; Lin-Ling WANG
The Chinese Journal of Clinical Pharmacology 2024;40(10):1419-1423
Objective To explore the effects of dydrogesterone combined with granulocyte colony-stimulating factor(G-CSF)on blood flow parameters and sex hormone levels in patients with thin endometrial(TE)infertility.Methods TE infertility patients were randomly divided into control group and treatment group.All patients were treated with freezing-thawing embryo transfer.The control group was treated with desdrogesterone after ovulation monitoring by vaginal ultrasound,10 mg each time,bid,and stopped until the 14th day after ovulation.In treatment group,G-CSF was given on the basis of control group,and the endometrial thickness and hemodynamic parameters were monitored by vaginal ultrasound 3 days later,and then embryo transfer was performed.Blood flow parameters,ultrasound parameters,endometrial morphology,sex hormone levels[follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),progesterone(P)]and pregnancy status were compared between the two groups.Results There were 49 cases in treatment group and 49 cases in control group.After treatment,endometrial thickness in treatment group and control group were(9.59±1.35)and(7.89±1.14)mm;follicle diameter were(19.35±1.58)and(17.75±1.42)mm;uterine volume were(92.68±7.85)and(85.69±6.74)cm3;PI were 1.29±0.27 and 1.74±0.32;RI were 0.32±0.09 and 0.50±0.11;peak systolic/end-diastolic velocity(S/D)were 2.03±0.28 and 2.21±0.25;P were(45.98±5.75)and(39.15±5.78)nmol·L-1;E2 were(462.58±58.42)and(339.45±45.97)pg·mL-1;FSH were(12.18±2.58)and(9.42±1.42)U·L-1;LH were(29.42±4.18)and(22.25±3.40)U·L-1;there were statistically significant differences between the two groups(all P<0.05).The clinical pregnancy rate(51.02%)and implantation rate(57.14%)in treatment group were higher than those in control group(30.61%and 36.73%),and the differences were statistically significant(all P<0.05).Conclusion Dydrogesterone combined with G-CSF can improve blood flow parameters,endometrial thickness and sex hormone levels in TE infertility patients,and help to increase the embryo implantation rate.
10.Effect of Ginkgo biloba extract in post-stroke depression model rats
Si-Min XIE ; You-Qiong WANG ; Miao-Miao MO ; Dong-Yi WANG ; Hai-Lan CHEN ; Bin YANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1933-1937
Objective To observe the effect of Ginkgo biloba extract(GBE)on depression like behavior in post stroke depression(PSD)model rats,and explore the mechanism of regulating Toll like receptor 4/nuclear factor-κ B(TLR4/NF-κB)pathway to inhibit neuroinflammation.Methods Rats were randomly divided into 6 groups,sham,cerebral ischemia,PSD,paroxetine,low-dose Ginkgo biloba extract(GBE-L)and high-dose Ginkgo biloba extract(GBE-H)groups,10 rats in each group.Except for the sham group,middle cerebral artery occlusion(MCAO)was performed to prepare a left focal cerebral ischemia model.Except for the sham group and cerebral ischemia group,other groups were subjected to chronic unpredictable mild stress(CUMS)to establish PSD rat model for 8 weeks.After 4 weeks of CUMS,the paroxetine group,GBE-L,and GBE-H were treated with paroxetine 5 mg·kg-1,GBE 50 mg·kg-1,and GBE 100 mg·kg-1,respectively.The sham group,cerebral ischemia group,and PSD group were treated with the same volume of 0.9%NaCl and continuously administered by gavage for 28 d.After 4 weeks and 8 weeks of CUMS,the body weight and sugar preference test were measured.Levels of serum tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β)and levels of norepinephrine(NE),serotonin(5-HT),and dopamine(DA)in the cerebral cortex were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of Tlr4,Nfkb1,and nuclear factor κ B-kinase subunit β inhibitory factor(Ikbkb)in the hippocampus of rats were detected by polymerase chain reaction.The protein levels of NF-κB,nuclear factor κB inhibitory protein α(IKBα)and phosphorylation nuclear factor κB inhibitory protein α(p-IKB)in hippocampal tissue were detected by Western blot.Results The body weights of rats in the sham group,cerebral ischemia group,PSD group,paroxetine group,GBE-L group and GBE-H group were(427.10±6.36),(403.10±7.37),(310.10±9.71),(355.00±4.03),(347.90±9.88)and(391.90±5.07)g;sugar preference rate were(93.93±1.78)%,(91.57±1.03)%,(54.72±7.34)%,(88.35±4.36)%,(63.55±12.73)%and(81.04±4.31)%;the levels of NE in the cerebral cortex were(1 951.14±52.86),(1 827.27±23.63),(1 662.12±35.92),(2 033.58±72.28),(1 887.31±33.07)and(2 175.00±42.54)pg·mL-1;the levels of 5-HT in the cerebral cortex were(237.07±8.86),(226.15±10.27),(214.51±3.46),(297.13±5.79),(274.14±7.63)and(285.34±8.72)ng·mL-1;the levels of DA in the cerebral cortex were(1 531.11±47.26),(1 209.89±58.09),(1 143.15±36.31),(1 812.67±51.28),(1 651.56±31.82)and(1 853.33±20.42)pg·mL-1.Compared with the PSD group,GBE significantly increased the body weight of rats(P<0.01)and increased the preference rate of sugar water in rats,showing the antidepressant like behavioral.GBE significantly reduced the levels of serum TNF-α,IL-1 β(all P<0.01),increased the levels of NE,5-HT,and DA in the cerebral cortex(all P<0.01),down regulate the mRNA levels of Tlr4,Nfkb1 and Ikbkb(P<0.05,P<0.01),reduced the expression of NF-κB(P<0.01),and reduced the phosphorylation of IKBα(P<0.01).Conclusion Ginkgo biloba extract can improve depression-like behavior in PSD model rats,and has antidepressant effect.Its mechanism is related to the inhibition of TLR4/NF-κB pathway,thus reducing neuroinflammation.

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