1.Neuroprotective effect and mechanism of eleutheroside B on Parkinson’s disease model mice by regulating the IKKβ/NF-κB signaling pathway
Xiaoli WANG ; Hua RONG ; Siwen PAN ; Chunlei YU ; Tianjiao XU ; Yu SUN ; Huan CONG ; Yu PANG ; Gang CHEN ; Xiaoming LI
China Pharmacy 2026;37(8):998-1002
OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B (ELB) on Parkinson’s disease (PD) model mice by regulating the IκB kinase β (IKKβ)/nuclear factor-κB (NF-κB) signaling pathway. METHODS Fifty mice were randomly divided into normal control group, model group, positive control group (selegiline hydrochloride, 10 mg/kg), and ELB low-dose and high-dose groups (80, 160 mg/kg), with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration, the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 30 mg/kg, for five consecutive days to establish the chronic PD model. After the last administration for 24 h, six mice were randomly selected from each group to test their behavioral abilities; detect the levels of interleukin-1β (IL-1β), IL-10, tumor necrosis factor-α (TNF-α) in brain tissue and their mRNA expressions were measured, and positive expression of tyrosine hydroxylase (TH), protein expressions of TH, α -synuclein ( α -syn), ionized calcium-binding adaptor molecule 1 (Iba-1), as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group, rotarod endurance time and climbing score of each administration group (except for the ELB low-dose group) were increased significantly ( P <0.05), while the levels and mRNA expressions of IL-1β, TNF-α, α -syn, and Iba-1, as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly (except for TNF-α in the ELB low-dose group). Conversely, the level and mRNA expression of IL-10 (except for the ELB low-dose group), TH positive expression and protein expressions were significantly increased ( P <0.05). Typical neurodegenerative pathological changes, such as neuronal karyopyknosis, mitochondrial swelling and vacuolization, and endoplasmic reticulum dilation, all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway, alleviating inflammatory responses, reducing abnormal α -syn aggregation and neuronal loss, and further improving motor dysfunction in PD mice.
3.Factors influencing home-based rehabilitation exercise and digital intervention needs among patients with spinal muscular atrophy: a qualitative study
Jiayin ZHENG ; Zihan XU ; Qingyu LI ; Yuhang ZHANG ; Siwen HUANG ; Xiaohu FU ; Guangyu ZHANG ; Wenzhu LI ; Qiao CHEN ; Qiqi WANG ; Sitong LUO
Chinese Journal of Rehabilitation Theory and Practice 2026;32(10):1194-1203
ObjectiveTo explore the factors influencing home-based rehabilitation exercise and the needs for digital interventions among patients with spinal muscular atrophy (SMA), based on the behavior change wheel (BCW), and to provide evidence for the development of digital home-based rehabilitation interventions. MethodsA two-phase qualitative study was conducted from December, 2024 to March, 2025. Using convenience sampling, 14 participants were recruited, including patients with SMA, primary caregivers, rehabilitation professionals, clinicians, a patient organization representative and a health policy expert. In phase 1, semi-structured individual interviews were conducted with seven participants, including patients, caregivers and a patient organization representative, to identify factors influencing home-based rehabilitation exercise and unmet needs. In phase 2, a focus group involving 12 stakeholders was conducted, including five participants who had participated in phase 1, to explore requirements for the functions, knowledge content and interface design of a digital intervention, five of them had participated in phase 1. Overall, the two phases involved 14 individual participants, accounting for 19 participant-instances. Thematic analysis was performed using both deductive and inductive approaches, guided by the capability-opportunity-motivation-behavior (COM-B) model. ResultsSix themes were identified. phase 1 showed that patients with SMA experienced inadequate continuity of rehabilitation services and limited access to professional rehabilitation resources, with interruptions in institution-based rehabilitation coexisting with declining adherence to home-based exercise. Home-based rehabilitation exercise was jointly influenced by capability-, opportunity- and motivation-related factors, including limited capabilities of patients and caregivers, constraints in time and supportive conditions and insufficient goals, feedback, and incentives. Individualized rehabilitation plans and professional guidance were the major unmet needs. phase 2 showed that the core functions of a digital intervention should include individualized exercise plans, professional guidance and feedback, reminders and incentives, safety monitoring, remote assessment, and privacy and permission management. Core knowledge content should include stratified exercise guidance, caregiving skills, recognition of abnormal conditions, and information on when and how to seek help. The interface should be simple, impose a low user burden and accommodate different types of users. ConclusionHome-based rehabilitation exercise among patients with SMA is jointly influenced by multiple capability-, opportunity- and motivation-related factors. Digital interventions should prioritize individualized rehabilitation plans, professional guidance and sustained behavioral support. These findings may inform the development of a digital home-based rehabilitation intervention prototype for patients with SMA; its feasibility, safety, clinical effectiveness and economic value require further evaluation.
4.Zishen Tiaogan Prescription Treats Diminished Ovarian Reserve in Rats via Keap1/Nrf2/HO-1 Signaling Pathway
Zhongtong LI ; Yaping ZHANG ; Chen YOU ; Qingqing LI ; Yingjie WANG ; Siwen OU ; Taomei XUE ; Chuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):72-80
ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve (DOR) and explore the role of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group (n=12) and a modeling group (n=36). The rats in the modeling group received subcutaneous injection of galactose (350 mg·kg-1) combined with immobilization stress daily. After 28 days of modeling, 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model, estradiol valerate (0.09 mg·kg-1), and low-, medium-, and high-dose (6.39, 12.78, 25.56 g·kg-1, respectively) Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels, respectively, of Nrf2, Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 (SOD2) in the ovarian tissue was detected by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed reduced follicles in the ovary, loose arrangement of the follicle granule layer, declined levels of anti-Mullerian hormone (AMH) and estradiol (E2) in the serum, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P<0.01), lowered levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.01), and increased accumulation of malondialdehyde (MDA) (P<0.01). In addition, the modeling led to up-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 and HO-1 protein was significantly decreased (P<0.01), the mRNA expression of Nrf2 was significantly decreased (P<0.05), the mRNA expression of HO-1 was significantly decreased (P<0.01), in the ovarian tissue. Compared with model group, the estradiol valerate and low-, medium-, and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index (P<0.01) and serum E2 and AMH levels (P<0.01), declined levels of FSH and LH (P<0.01), increased follicles in the ovary, elevated levels of SOD, CAT, and GSH, and reduced accumulation of MDA (P<0.05, P<0.01). Furthermore, these groups showcased down-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 protein was significantly increased (P<0.01), the expression level of HO-1 protein was increased (P<0.05,P<0.01), and increased positive expression of SOD2 (P<0.01). ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones, down-regulate the expression of Keap1, up-regulate the expression of Nrf2, HO-1, and SOD2, enhance the antioxidant capacity, and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.
5.Zishen Tiaogan Prescription Treats Diminished Ovarian Reserve in Rats via Keap1/Nrf2/HO-1 Signaling Pathway
Zhongtong LI ; Yaping ZHANG ; Chen YOU ; Qingqing LI ; Yingjie WANG ; Siwen OU ; Taomei XUE ; Chuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):72-80
ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve (DOR) and explore the role of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group (n=12) and a modeling group (n=36). The rats in the modeling group received subcutaneous injection of galactose (350 mg·kg-1) combined with immobilization stress daily. After 28 days of modeling, 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model, estradiol valerate (0.09 mg·kg-1), and low-, medium-, and high-dose (6.39, 12.78, 25.56 g·kg-1, respectively) Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels, respectively, of Nrf2, Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 (SOD2) in the ovarian tissue was detected by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed reduced follicles in the ovary, loose arrangement of the follicle granule layer, declined levels of anti-Mullerian hormone (AMH) and estradiol (E2) in the serum, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P<0.01), lowered levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.01), and increased accumulation of malondialdehyde (MDA) (P<0.01). In addition, the modeling led to up-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 and HO-1 protein was significantly decreased (P<0.01), the mRNA expression of Nrf2 was significantly decreased (P<0.05), the mRNA expression of HO-1 was significantly decreased (P<0.01), in the ovarian tissue. Compared with model group, the estradiol valerate and low-, medium-, and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index (P<0.01) and serum E2 and AMH levels (P<0.01), declined levels of FSH and LH (P<0.01), increased follicles in the ovary, elevated levels of SOD, CAT, and GSH, and reduced accumulation of MDA (P<0.05, P<0.01). Furthermore, these groups showcased down-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 protein was significantly increased (P<0.01), the expression level of HO-1 protein was increased (P<0.05,P<0.01), and increased positive expression of SOD2 (P<0.01). ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones, down-regulate the expression of Keap1, up-regulate the expression of Nrf2, HO-1, and SOD2, enhance the antioxidant capacity, and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.
6.Knowledge and behaviors about hepatitis B prevention and control among carriers of hepatitis B surface antigen
LI Siwen ; ZHOU Tiantian ; ZHANG Chao ; ZHANG Dan ; HU Weijun
Journal of Preventive Medicine 2025;37(3):253-256,261
Objective:
To investigate the knowledge and behaviors related to hepatitis B prevention and control among carriers of hepatitis B surface antigen (HBsAg), so as to provide the basis for conducting health education and interventions for HBsAg carriers.
Methods:
Based on the seroepidemiological survey of hepatitis B among individuals aged 1 to 69 years in Shaanxi Province, HBsAg carriers were selected as the study subjects. Basic information, knowledge and behaviors about hepatitis B prevention and control were collected through questionnaire surveys. The awareness of hepatitis B prevention and control knowledge and related behaviors among HBsAg carriers were analyzed.
Results:
A total of 107 HBsAg carriers were enrolled, including 52 males (48.60%) and 55 females (51.40%), and had a median age of 47.04 (interquartile range, 19.78) years. The awareness of hepatitis B prevention and control knowledge ranged from 56.07% to 87.85% among HBsAg carriers, with the highest awareness for "hepatitis B vaccination can effectively prevent hepatitis B "(87.85%), and the lowest awareness for "sharing meals with HBsAg carriers or hepatitis B patients will not lead to infection" (56.07%) and "hepatitis B can be treated with antiviral drugs" (61.68%). The proportions of those who did not seek medical consultation, undergo regular check-ups, or receive treatment were relatively high, at 65.42%, 72.90% and 77.57%, respectively.
Conclusions
The awareness of hepatitis B transmission routes and treatment-related knowledge among HBsAg carriers is relatively low, and their medical-seeking behaviors are relatively passive. There is a need to enhance the dissemination of hepatitis B prevention and control knowledge, improve medical-seeking behaviors, and reduce the risk of hepatitis B virus transmission.
7.GLP-1RAs attenuated obesity and reversed leptin resistance partly via activating the microbiome-derived inosine/A2A pathway.
Chunyan DONG ; Bailing ZHOU ; Binyan ZHAO ; Ke LIN ; Yaomei TIAN ; Rui ZHANG ; Daoyuan XIE ; Siwen WU ; Li YANG
Acta Pharmaceutica Sinica B 2025;15(2):1023-1038
Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)2-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)2-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)2-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)2-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)2-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.
8.Gas signaling molecules activate cGAS-STING signaling pathway in tumor immunotherapy
Siwen WANG ; Weiwei LIN ; Yuanyuan CHENG ; Shaobo DUAN ; Yan ZHANG ; Youmei PENG ; Zhuangli ZHANG ; Jinglu SHI ; Na LI ; Longjun MA
Immunological Journal 2025;41(2):110-116
Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.
9.Safety evaluation of tetravalent meningococcal conjugate vaccine in combination with the inactivated poliomyelitis vaccine and diphtheria-tetanus-acellular pertussis vaccine for infants
Siwen LI ; Xiaoyu LIU ; Ruize WANG ; Chao ZHANG ; Yake LYU ; Weijun HU
Chinese Journal of Preventive Medicine 2025;59(3):271-276
Objective:To investigate the safety of the tetravalent meningococcal conjugate vaccine (MPCV-ACYW) in combination with the inactivated poliomyelitis (IPV) vaccine and diphtheria-tetanus-acellular pertussis (DTaP) vaccine for infants aged 3-5 months and provide real-world evidence for the immunization strategy of vaccine combination.Methods:From June to October 2023, a total of 600 3-month-old infants were selected and divided into three groups: control group, mono-vaccination group and combined vaccination group. They were simultaneously or individually vaccinated with MPCV-ACYW, IPV and DTaP vaccines at 3, 4, and 5 months of age, respectively. The incidence rate of adverse reactions within 30 days after each dose was observed.Results:All 600 infants completed at least one vaccination and entered the safety data analysis. The age of the control group (100 infants), the mono-vaccination group (250 infants), and the combination group (250 infants) was (101.20±7.88), (102.26±7.94), and (102.35±7.76) days, respectively. The body lengths were (63.00±3.02), (62.55±3.06), and (63.14±4.02) cm, respectively. The body weights were (6.90±0.77), (6.86±0.94), and (6.99±0.95) kg, respectively. Boys accounted for 49%, 50.4%, and 52.4%, respectively, with no statistically significant differences (all P>0.05). The overall incidence rates of adverse reactions in the control group, mono-vaccination group, and combined vaccination group were 4.00%, 2.80%, and 3.20%, respectively, with systemic adverse reaction rates of 3.00%, 2.40%, and 2.00%. The incidence rates of local adverse reactions were 1.00%, 0.40%, and 1.20%, with no statistically significant differences (all P>0.05). Adverse reactions were mainly grade 1, with incidence rates of grade 1 adverse reactions of 3.00%, 2.00%, and 1.60% in the three groups, and incidence rates of grade 2 adverse reactions of 1.00%, 0.80%, and 1.60%, respectively. No grade 3 or 4 serious adverse reactions occurred, and the differences were not statistically significant (all P>0.05). The adverse reaction symptoms of the three groups were mainly systemic reactions, among which fever and diarrhea symptoms were reported in individual cases in each group, with no statistically significant differences in the incidence rate (all P>0.05). The symptoms of adverse reactions were mostly transient and self-relieved, all of which were cured. Conclusion:The combination of MPCV-ACYW and IPV or DTaP vaccines is safe for infants aged 3-5 months.
10.Attentional processing of verbal emotional information in college students with subclinical depression
Yutong LI ; Siwen ZHENG ; Xueli WANG ; Xin YUE
Chinese Mental Health Journal 2025;39(11):988-993
Objective:To examine the attentional processing of verbal emotional information in college students with subclinical depression.Methods:Fifty college students were recruited(24 with subclinical depression group and 26 in the control group)were recruited from a university in Liaoning Province to investigate the atten-tional bias of subclinically depressed college students towards verbal emotional information(experiment 1).In addi-tion,48 college students(20 with subclinical depression and 28 in the control group)were recruited to investigate the attention disengagement of subclinically depressed college students from verbal emotional information(experi-ment 2).In experiment 1,two groups passively viewed words and recorded the eye movement data of emotional words.In experiment 2,two groups were asked to watch the emotional word-neutral word pair.When color borders were presented around neutral words,the attention disengagement latency that was the time taken by the eye saccade from emotional words to neutral words was recorded.Results:The results of experiment 1 showed that the total fix-ation duration of negative words in the subclinical depression group was longer than that in the control group(P<0.01).The results of experiment 2 showed that attention disengagement latency of negative words in the subclinical depression group was longer than that in the control group(P<0.05).Conclusion:College students with subclini-cal depression exhibit attentional bias towards negative verbal information and difficulties in attentional disengage-ment.

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