1.Mechanism of Shoutaiwan in Treatment of Recurrent Spontaneous Abortion: A Review
Xue DANG ; Feixiang LIU ; Yanchen FENG ; Zhiying CHE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):283-291
Recurrent spontaneous abortion (RSA) is a common gynecological disease during pregnancy, clinically characterized by repeated spontaneous abortions, yet its pathological mechanism remains incompletely understood. Traditional Chinese medicine attributes the pathogenesis of RSA to the deficiency of Chong Ren and the lack of fetal solidity. It has amassed experience in treating RSA, with Shoutaiwan being widely utilized for addressing miscarriage symptoms such as habitual abortion due to kidney deficiency, bleeding during pregnancy, and fetal movement. In recent years, there has been a gradual increase in experimental studies on the application of Shoutaiwan in treating RSA and on related experiments. These studies have demonstrated that Shoutaiwan preserves the fetus mainly by modulating hormone balance, alleviating immune inflammation, and enhancing blood coagulation equilibrium during pregnancy. Besides, through the modulation of key signaling pathways such as nuclear factor, erythroid 2 like 2 (Nrf2)/heme oxygenase-1 (HO-1) and Janus kinase 1 (JAK1)/signal transducer and activator of transcription (STAT), as well as mitogen-activated protein kinase (MAPK), Shoutaiwan has improved cellular antioxidant capacity, adjusted the phenotype of trophoblast and metaphase cells, and inhibited immune rejection, thus improving the pregnancy success rate. These findings not only elucidate the diverse biological foundations underlying Shoutaiwan's efficacy in treating RSA but also offer a scientific rationale for its clinical application and further mechanism research. Nonetheless, there remains a dearth of systematic reviews on RSA treatment with Shoutaiwan. Therefore, this review summarizes and synthesizes existing research findings to systematically analyze existing literature and studies, delving deeply into the principal pharmacological effects and associated signaling pathways of Shoutaiwan in regulating RSA. It aims to establish crucial reference points for its clinical application in RSA treatment and future experiments and research.
2.Treatment of Cerebral Ischemia-reperfusion Injury by Traditional Chinese Medicine Based on PI3K/Akt Signaling Pathway: A Review
Jing GAO ; Feixiang LIU ; Yunke ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):253-261
Cerebral ischemia/reperfusion injury (CIRI) is a complex cascade reaction process in which the blood flow and oxygen supply of brain tissue in the infarcted area recover after cerebral ischemia, resulting in secondary injury of ischemic brain tissue. At present, thrombolysis as soon as possible and restoration of cerebral blood supply are still the only strategies for the treatment of stroke, but a considerable number of patients' symptoms will be more serious after reperfusion, making patients face adverse outcomes such as neurological function injury and even death and seriously affecting the quality of life and safety of patients. Therefore, an in-depth exploration of the mechanism and treatment strategy of CIRI has important clinical significance. The phosphatidylinositol 3- kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the classic anti-apoptosis/reproductive-promoting signal transduction pathways, which is responsible for cell proliferation, growth, and differentiation. It is the key cascade signaling pathway of CIRI, located at the core site in many mechanisms such as mitochondrial disorder, apoptosis, autophagy, oxidative stress, and inflammation. It is closely related to the occurrence and development of CIRI. Traditional Chinese medicine has been used in the clinical treatment of stroke and its complications for thousands of years, and the clinical effect of traditional Chinese medicine in the prevention and treatment of CIRI has been affirmed by a large number of research results in recent years. It is further clarified that the monomers, active components, and their compound prescriptions of traditional Chinese medicine can directly or indirectly regulate the PI3K/Akt signaling pathway by virtue of the biological advantages of multi-targets, multi-components, and multi-pathways and play an overall protective role in CIRI. By analyzing the related research progress of traditional Chinese medicine in China and abroad in recent years, the authors summarized the role and mechanism of regulating the PI3K/Akt signaling pathway in the prevention and treatment of CIRI, so as to provide further theoretical basis for the study of the mechanism of clinical prevention and treatment of CIRI.
3.Shugan Jianpi Yangxin Prescription Regulates Orexin-A and Its Receptors in Mouse Model of Insomnia
Zhen WANG ; Jie ZHANG ; Feixiang LIU ; Jiangyan SUN ; Yahui GAO ; Yuxin ZHENG ; Min ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):54-61
ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A (OXA), orexin-1 receptor (OX1R), and orexin-2 receptor (OX2R) in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine (PCPA). Fifty BALB/c mice were randomized into a blank group, a model group, an eszopiclone (0.13 mg·kg-1) group, and low- and high-dose (8.4 and 33.6 g·kg-1, respectively) Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored, and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry (IHC) was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine (5-HT) in the hypothalamus, serum, and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA, OX1R, and OX2R in the hypothalamus. ResultCompared with the blank group, the model group had decreased body weight (P<0.01), increased escape latency (P<0.01), increased sleep latency (P<0.01), shortened sleep duration (P<0.01), elevated OXA level and lowered 5-HT level in the hypothalamus, serum, and spleen (P<0.05), and up-regulated mRNA levels of OXA, OX1R, and OX2R in the hypothalamus (P<0.01). Compared with the model group, the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight (P<0.05, P<0.01), shortened escape latency (P<0.05), shortened sleep latency and prolonged sleep duration (P<0.01), and lowered OXA level and elevated 5-HT level in the hypothalamus, serum, and spleen (P<0.05, P<0.01). Moreover, the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA, OX1R, and OX2R in the hypothalamus (P<0.01). ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.
4.Traditional Chinese Medicine in Treatment of Parkinson's Disease by Regulating TLR4/NF-κB Signaling Pathway: A Review
Qingge WANG ; Feixiang LIU ; Yunke ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):225-235
Parkinson's disease (PD) is a common neurological degenerative disease in the middle-aged and elderly, characterized by pathological changes of progressive degeneration of dopaminergic neurons in the substantia nigra and Lewy body formation, with high prevalence and long course of disease. The drug is mainly used to treat PD in western medicine, and the early curative effect is remarkable. However, with the progression of the disease and the long-term use of the drug, the efficacy will be significantly reduced, or there may be sports complications, and the long-term efficacy is not good. As a traditional medical system, traditional Chinese medicine has a unique understanding of PD. Traditional Chinese medicine plays an important role in the treatment of PD, which is natural, mild, safe, and effective, and it can cooperate with western medicine to enhance its efficacy and reduce the adverse reactions of western medicine. The pathogenesis of PD is complex, involving multiple levels such as mitochondrial dysfunction and apoptosis. Neuroinflammation is also involved in the progressive degeneration of dopaminergic neurons in PD. The Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway is a classic inflammatory pathway, and its expression changes play an important role in the occurrence and development of inflammatory response in the body. In recent years, the research on this pathway in TCM is increasing. This paper summarized the literature of traditional Chinese and western medicine in the past 10 years and reviewed the relevant mechanism of TCM regulation of TLR4/NF-κB pathway in the treatment of PD from the aspects of TCM monomer, compound, and other TCM therapies, so as to provide some references for the search for new targets of drug therapy and gene therapy and the in-depth study of TCM prevention and treatment of PD.
5.Effect of traditional Chinese medicine and compounds for supplementing qi and activating blood circulation and inducing resuscitation on regulating stem cells to promote nerve repair of acute ischemic stroke
Chunmiao YING ; Xiaolong PAN ; Feixiang LIU ; Na CHEN ; Feiyan FAN ; Yunke ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(1):121-130
BACKGROUND:Endogenous neurogenesis and exogenous stem cell transplantation in the brain show great therapeutic potential for neurological diseases including ischemic stroke,repairing and replacing lost neurons,promoting synaptic remodeling,and inhibiting apoptosis.Traditional Chinese medicine and compound therapy for supplementing qi,activating blood circulation and inducing resuscitation for the treatment of neurological dysfunction after ischemia have certain advantages,targeting nerve repair through a variety of ways,including promoting endogenous neurogenesis and exogenous stem cell survival,proliferation,homing,and inducing neuronal differentiation. OBJECTIVE:To summarize the mechanism of traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke,in order to provide a reference for the research and treatment of new drugs in ischemic stroke. METHODS:The articles from CNKI and PubMed databases about traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation in promotion of nerve repair in the acute phase of ischemic stroke from 2010 to 2022 were searched,with"supplementing qi and activating blood circulation;inducing resuscitation;traditional Chinese medicine(TCM);compounds;ischemic stroke;nerve repair;stem cells"as Chinese and English search terms.After excluding old and duplicate views,the retrieved literature was analyzed and collated,and a total of 124 articles were included for analysis. RESULTS AND CONCLUSION:(1)The definition of stem cells,ischemic stroke and the nerve repair pathway in the acute phase of ischemic stroke were sorted out.(2)The mechanism of action of traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke was summarized,mainly including promoting stem cell proliferation,improving stem cell viability and survival rate,promoting nerve cell homing,inducing stem cell differentiation to neurons,inhibiting apoptosis of nerve cells,promoting axon regeneration,regulating angiogenesis and remodeling,improving the level of neurotrophic factors and repairing the integrity of the blood-brain barrier.(3)Through the existing research,the relevant factors and signaling pathways of traditional Chinese medicines and compounds for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke were summarized,such as Nestin protein expression,DCX protein expression,brain-derived neurotrophic factor,vascular endothelial growth factor and Wnt/β-catenin signaling pathway,Notch signaling pathway,PI3k/Akt signaling pathway,BDNF/TrkB signaling pathway and ERK/MAPK signaling pathway.It provides a relevant reference for future research on ischemic stroke-specific drugs and new clinical treatment methods.
6.Effect and mechanism of traditional Chinese medicine on inhibiting the aging of mesenchymal stem cells
Xiaolong PAN ; Feiyan FAN ; Chunmiao YING ; Feixiang LIU ; Yunke ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(7):1091-1098
BACKGROUND:The aging of mesenchymal stem cells is one of the main causes of aging-related diseases,and seriously affects its clinical application.Traditional Chinese medicine has a good anti-aging effect,and it can inhibit the aging of mesenchymal stem cells to promote its application in tissue engineering and prevent and treat aging-related diseases. OBJECTIVE:To review the effect and mechanism of traditional Chinese medicine on inhibiting the aging of mesenchymal stem cells. METHODS:We searched CNKI and PubMed for the literature on inhibiting mesenchymal stem cell aging with traditional Chinese medicine from 2012 to 2022.The keywords were"traditional Chinese medicine,mesenchymal stem cells(MSCs),aging"in Chinese and English,respectively.Finally,92 articles were included for further review. RESULTS AND CONCLUSION:(1)We summarized five main mechanisms of the aging of mesenchymal stem cells:DNA damage,telomere shortening,oxidative stress,autophagy disorder and mitochondrial dysfunction.(2)This paper reviewed the phenotypic characteristics of senescent mesenchymal stem cells,including increases in cell volume,decreases in proliferation and multi-directional differentiation,increases in β-galactosidase activity,and activation of p21 and p16 pathways,and so on.(3)We summarized the main mechanisms of Chinese medicine inhibiting the senescence of mesenchymal stem cells at present,including inhibiting the activation of the Wnt pathway,inhibiting the production of mitochondrial reactive oxygen species,promoting the silencing of information regulator factor 2 homolog 1,phosphatidylinositol 3-kinase/protein kinase B,adenosine 5'-monophosphate-activated protein kinase and nuclear factor E2 related factor 2 pathway activation,and promoting the expression of telomerase reverse transcriptase.(4)At present,bone marrow mesenchymal stem cells are the most widely studied in the research of traditional Chinese medicine to inhibit the aging of bone marrow mesenchymal stem cells,and the effect is better.(5)Zuogui Wan,Bushen Tiaogan Formula,resveratrol,Astragalus membranaceus and other traditional Chinese medicines can prevent and treat osteoporosis by promoting the proliferation and osteogenic differentiation of aging mesenchymal stem cells.However,the mechanism of Chinese medicine in improving the paracrine function of mesenchymal stem cells and preventing other aging-related diseases by inhibiting the aging of mesenchymal stem cells needs to be further explored.
7.Modified Tongqiao Huoxuetang Down-regulates PI3K/Akt Pathway to Treat Basilar Artery Dolichoectasia
Feixiang LIU ; Daopei ZHANG ; Zhaoxin WU ; Huailiang ZHANG ; Yunke ZHANG ; Jinxin MIAO ; Zhenqiang ZHANG ; Ruiqin SUN ; Lixiang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):87-94
ObjectiveTo establish a mouse model of basilar artery dolichoectasia (BAD) and explore the mechanism of modified Tongqiao Huoxuetang (JTQHX) in regulating BAD via phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. MethodSixty C57/BL6 female mice were randomized into sham operation (injected with 10 U·mL-1 inactivate elastase), model, atorvastatin calcium tablets (2.6 mg·kg·d-1), and low- and high-dose (crude drug 3.4, 17 g·kg-1·d-1, respectively) JTQHX groups. The mouse model of BAD was established by injection with 10 U·mL-1 elastase. After 14 days of modeling, the sham operation group and model group were administrated with equal volumes of pure water by gavage, and other groups with corresponding drugs for 2 months. The levels of interleukin-6 (IL-6) and calpain (LpA) in the serum were measured by enzyme-linked immunosorbent assay (ELISA). Verhoeff 's Van Gieson (EVG) staining was employed to observe the pathological changes of blood vessels. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was employed to examine the apoptosis rate of vascular smooth muscle cells (VSMCs). Image Pro Plus was used to observe and calculate the curvature index, elongation length, percentage increase in vessel diameter, and curvature angle of the basilar artery vessels in mice. Western blot was employed to determine the expression levels of PI3K and Akt in the vascular tissue. ResultCompared with the sham operation group, the model group showed lowered IL-6 level (P<0.01), no significant change in LpA level, increased apoptosis of VSMCs (P<0.01), and increased curvature index, elongation length, percentage increase in vessel diameter, and curvature angle (P<0.01). Furthermore, the modeling up-regulated the protein levels of PI3K and Akt in blood vessels (P<0.01) and aggravated the destruction of the inner elastic layer, atrophy of the muscular layer, and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. Compared with the model group, 2 months of treatment with JTQHX elevated the IL-6 level (P<0.01), reduced the apoptosis of VSMCs (P<0.01), decreased the curvature index, elongation length, percentage increase in vessel diameter, and curvature angle (P<0.05, P<0.01), and down-regulated the protein levels of PI3K and Akt in blood vessels (P<0.01). In addition, the treatment alleviated the destruction of the inner elastic layer, atrophy of the muscular layer, and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. ConclusionJTQHX inhibits the elongation, expansion, and curvature of basilar artery vessels and alleviates the pathological changes by reducing the apoptosis of VSMCs and down-regulating the expression of PI3K/Akt pathway.
8.Action mechanism of traditional Chinese medicine and mesenchymal stem cells regulating immune response in treatment of amyotrophic lateral sclerosis
Shaona WANG ; Chen GAO ; Feiyan FAN ; Feixiang LIU ; Yunke ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(25):4087-4093
BACKGROUND:Amyotrophic lateral sclerosis is a progressive neurodegenerative disease,which often leads to the death of neurons in the brain and spinal cord.The pathogenesis of amyotrophic lateral sclerosis is extremely complex,with high refractory rate and mortality rate.There are only two kinds of drugs for its treatment,so it is urgent to develop new treatment methods to improve the prognosis of patients. OBJECTIVE:To review the mechanism of Chinese medicine and mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis. METHODS:"Traditional Chinese medicine,medical stem cells,ALS,immune response"were Chinese and English search terms.Articles were retrieved from WanFang,CNKI,PubMed,Web of Science and other databases from 2010 to 2023.Finally,69 articles were included for review. RESULTS AND CONCLUSION:(1)The article summarizes in detail the five mechanisms of traditional Chinese medicine regulating the immune response in the treatment of amyotrophic lateral sclerosis:mainly including the promotion of expression of closed zone protein-1 and closed protein-5 by traditional Chinese medicine such as borneol and astragaloside IV to rebuild the integrity of the blood central nervous system barrier.Fufangteng Mixture can regulate the receptor molecules on the surface of the natural killer cells to inhibit their autotoxicity.The complement system factors such as Scutellaria barbata and patchouli can inhibit their abnormal activation.Tripterygium wilfordii and Uncaria rhynchophylla inhibit the activation of microglia by mediating the production of extracellular signal-regulated kinase 1/2 attenuated inducible nitric oxide synthase.Zuogui Pill and Trichosanthes kirilowii Root promote the expression of interleukin-10 and regulate T cells to improve the immune environment.(2)Through existing research,five mechanisms of mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis have been summarized,mainly including reducing the expression of aquaporin 4 and reducing endothelial nitric oxide synthase signal transduction to repair the integrity of the immune barrier;releasing indoleamine 2,3-dioxygenase,prostaglandin E2 and other factors to resist natural killer cell toxicity;secretion factor H interferes with the activity of invertase and inhibits abnormal activation of the complement system;regulating the CX3CL1/CX3CR1 system axis or secreting transforming growth factors β,which can change the phenotype of microglia and inhibit its activity by other ways;increasing the expression of interleukin-10 or activating the STATS phosphorylation pathway to restore T cell function.(3)At present,there are few studies on the combination of traditional Chinese medicine and mesenchymal stem cells in the treatment of amyotrophic lateral sclerosis.Relevant research reports have shown that Jiweiling Injection can promote stem cell proliferation and differentiation and that Buyang Huanwu decoction combined with bone marrow mesenchymal stem cells can significantly improve the integrity of the blood-brain barrier.In the future,further exploration is needed to explore the synergistic treatment effect of both on refractory amyotrophic lateral sclerosis.
9.The Association between Screen Time Behavior in Early Childhood,Outdoor Activities and their Interaction with Hyperactive Behavior in Preschool Children
Huiting CHEN ; Yulan WU ; Feixiang ZENG ; Dongyan WEN ; Weiying LIU ; Ruoqing CHEN ; Lvping LI ; Yu JIN
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(6):891-901
[Objective]To investigate the association between screen content and the frequency of screen exposure at the age of one and a half years and hyperactive behavior in preschool,and to explore how the association is affected by the interaction between outdoor activities and screen behaviors,which could provide theoretical basis and feasible solutions for the prevention and intervention of behavioral problems in childhoood.[Methods]The survey was conducted from June 2022 to June 2023 in Huicheng District,Huizhou (China) stratified by whole cluster sampling methods. Parents and teachers of 5648 children in 61 kindergartens were sampled for questionnaire surveys. The Conners Teacher Rating Scale (TRS) was used to investigate hyperactive behavior. A self-administered questionnaire was used to investigate basic demographic information of children,screen content,frequency of screen exposure and outdoor activities at the age of one and a half years. Multivariate logistic regression was used to explore the association between video screen behavior and hyperactive behavior and its interaction with outdoor activities by controlling for covariates such as children's age,gender,and parental education.[Results]Result showed the overall prevalence of 3.2% for hyperactive behavior,2.1% for conduct problems,2.1% for hyperactivity problems,1.3% for inattention-passivity problems,and 0.9% for hyperactivity index. After adjusting for confounding factors,multiple logistic regression analysis showed that screen exposure of "two to four times a week" at one and a half years old was associated with an increased detection rate of hyperactive behaviors in preschool children,with an estimated ORs (95% CI) of 1.682 (1.141,2.480). Daily screen exposure was associated with increased detection rates of hyperactive behavior,conduct problems,hyperactivity issues,inattention-passivity problems,and hyperactivity index in pre-school age. The estimated ORs (95% CI) were 2.136 (1.218,3.746),2.321 (1.185,4.546),2.300 (1.208,4.380),2.776 (1.267,6.085) and 3.640 (1.525,8.687),respectively. But the above associations were not found in children who were engaged in daily outdoor activities at the age of one and a half years (P value for interaction<0.001). No association was found between screen content and hyperactive behavior (P>0.05).[Conclusions]Frequency of screen exposure in early childhood is significantly associated with hyperactive behavior problems in preschool,and outdoor activities could weaken the correlation between high-frequency screen exposure and hyperactive behavior,suggesting that parents and schools should prioritize scientifically guiding children's video viewing behavior and outdoor activities,ensuring a well-arranged daily life,to lay a good foundation for the healthy development of children's behavior.
10.A Validity Analysis of the Measurement of Depression and Anxiety in Employees
Feixiang ZHOU ; Jing LIU ; Zemin LIU
Chinese Journal of Health Statistics 2024;41(3):349-353
Objective To evaluate the validity of the Patient Health Questionnaire(PHQ-9)and the Generalized Anxiety Disorder Scale(GAD-7)in measuring depression and anxiety among employees.Methods A stratified random sample of 1117 employees from various departments of an enterprise was included in the study.The item analysis was performed using the Grade Response Model in IRT to assess the dimensionality,discrimination,difficulty coefficient and average information of each item.The model fit and differential item functioning were also assessed.Results The study population consisted of 661(59.2%)employees under the age of 45 and 456(40.8%)employees aged 45 and above;802(71.8%)were male and 315(28.2%)were female.The Cronbach's α coefficients for the PHQ-9 and GAD-7 were 0.923 and 0.951,and the split-half reliability coefficients were 0.863 and 0.940.The ratio of the first characteristic root to the second characteristic root of both the PHQ-9 and GAD-7 scales was>3,in line with the hypothesis of unidimensionality.The discrimination of the PHQ-9 items ranged from 2.362 to 3.618,the difficulty coefficient from-0.949 to 2.639,and the average information from 0.772 to 1.935.The discrimination of the GAD-7 items ranged from 3.631 to 5.580,the difficulty coefficient from-0.469 to 2.044,and the average information from 1.880 to 3.547.Differential item functioning indicated that age and gender did not influence the screening of the two scales.Conclusion The PHQ-9 and GAD-7 scales can be used as psychometric tools to assess depression and generalized anxiety disorder in corporate employees.

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