Ischemic stroke （IS） is an acute cerebrovascular disease caused by insufficient blood supply to the brain， resulting in brain tissue necrosis and neurological dysfunction. It is characterized by impaired motor， language， sensory， cognitive， and other functions. The pathogenesis involves inflammatory responses， excitotoxicity of excitatory amino acids， and mitochondrial dysfunction. IS with a high incidence， high mortality， high disability， and a high recurrence rate is the leading cause of death in China. At present， Western medical therapies mainly focus on vascular recanalization， including thrombolysis and mechanical thrombectomy. However， due to the possibility of cerebral hemorrhage and edema， narrow time windows， and contraindications associated with intravascular therapy， only a few patients can benefit from these therapies， which greatly limit their clinical application. IS belongs to the categories such as stroke， hem iplegia， and major syncope in traditional Chinese medicine （TCM）. It is mainly caused caused by wind， fire， phlegm， and stasis， which lead to imbalance of Yin and Yang， disorder of Qi and blood， and invasion of clear orifices. The common treatment methods include calming the liver and dispelling wind， resolving phlegm and unblocking meridians， and activating blood and resolving stasis. TCM acting on multiple pathways and targets with low toxicity and side effects has definite effects in improving the prognosis and reducing the recurrence rate， being worthy of promotion and research. Brain-derived neurotrophic factor （BDNF） plays a key role in promoting neurogenesis and increasing synaptic plasticity. During the progression of IS， BDNF binds to tyrosine kinase receptor B （TrkB） to initiate intracellular signaling cascades， thus exerting neuroprotective effects. Studies have shown that TCM can regulate the BDNF/TrkB signaling pathway， treating IS by regulating synaptic plasticity and promoting neural repair. This paper summarizes and generalizes the mechanisms of active components， single herbs， and compound prescriptions of TCM in regulating the BDNF/TrkB signaling pathway in the treatment of IS through the review of domestic and foreign literature in recent years， aiming to provide a theoretical basis and treatment reference for the treatment of IS with TCM.

OBJECTIVES: To exple the mechanism of Qixiong Zuogui Granules (QXZG) for enhancing synaptic plasticity in aging rats. METHODS: Forty SD rats were randomized into control group, aging model group, donepezil treatment group, and QXZG treatment group (n=10). Except for the control rats, all the rats were subjected to daily intraperitoneal injection of D-galactose for 8 consecutive weeks to induce brain aging, and donepezil hydrochloride and QXZG suspension were administered by gavage during modeling. After the interventions, the rats were evaluated for general conditions, behavioral changes, oxidative stress indicators, hippocampal pathologies, and expressions of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, p16, and synaptic plasticity-associated proteins. RESULTS: The rats in the model group exhibited obvious aging phenotypes such as yellowing of the teeth and hair, body weight loss, and impaired learning and memory abilities, with decreased serum SOD and GSH-Px activities and increased serum MDA level. The rat models also showed obvious pathological changes, reduced Nissl bodies, and elevated p16 protein expression in the hippocampal CA1 region, with significantly decreased expression levels of BDNF, TrkB, CREB and synaptic plasticity proteins SYN, GAP43, and PSD95. Treatment with QXZG alleviated the aging phenotypes in the rat models, improved their learning and memory abilities and pathological changes in the hippocampal CA1 region, reduced oxidative stress and p16 protein expression, and promoted the expressions of the BDNF/TrkB pathway proteins and synaptic plasticity proteins. CONCLUSIONS QXZG enhances synaptic plasticity and reduces oxidative stress in aging rats possibly by upregulating the BDNF/TrkB signaling pathway proteins, thereby delaying brain aging and improving learning and memory abilities of the rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Neuronal Plasticity/drug effects* ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Receptor, trkB/metabolism* ; Rats ; Aging ; Drugs, Chinese Herbal/pharmacology* ; Male ; Oxidative Stress ; Hippocampus/metabolism*

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.

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.

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.

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.

Primary liver cancer is a malignant tumor with high morbidity and mortality. It also ranks in the forefront in the incidence and mortality of malignant tumors in China, which seriously threatens the lives and health of Chinese people. Most patients have already been in the intermediate and late stage when they are diagnosed, thus the chance of surgery is lost, and the prognosis is poor. In recent years, with the advancement of vascular interventional therapy technologies such as hepatic arterial chemoembolization and hepatic arterial infusion chemotherapy, the emergence of new tyrosine kinase inhibitors, immune checkpoint inhibitors, and especially the development of multimodal combination therapy, the treatment effect of unresectable hepatocellular carcinoma has been continuously improved, and it also provides a potential possibility for sequential surgical treatment. This article reviews the research progress of vascular interventional therapy combined with systemic therapy in unresectable hepatocellular carcinoma, in order to provide a reference for the clinical treatment of unresectable hepatocellular carcinoma.

Objective:To observe any effect of low-frequency whole body resonant stimulation on the ba-lance and walking ability of hemiplegic stroke survivors.Methods:Sixty-six stroke survivors with hemiplegia were randomly divided into a low-frequency resonance training group, a high-frequency vibration training group and a control group, each of 22. All received routine exercise training at individualized intensities. All three groups underwent five 1-minute cycles of 7Hz, 15Hz or 1Hz stimulation twice a day, five days a week for eight weeks. Before and after the intervention, balance and walking ability were evaluated using the Berg Balance Scale, the timed up and go test and a 10m walking test. Step length, step frequency and step speed were also measured.Results:There were no significant differences among the three groups before the training. Afterward, significant improvement was observed in all of the groups in terms of all of the measurements. The average results of the low-frequency resonance training group were at that point significantly better than the other two groups′ averages, while the high-frequency vibration training group′s results were superior to those of the control group.Conclusion:Resonance training at 7Hz is the most effective in improving the balance and walking ability of stroke survivors with hemiplegia.

Humans ; Hemangioma, Cavernous/diagnostic imaging* ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging

Objective:To observe the intervention mechanism of phlegm-stasis co-treatment for the JNK signaling pathway in the myocardium of diabetes rats.Methods:Totally 50 male SD rats of SPF grade were selected. Diabetes model was established by single intraperitoneal injection of 55 mg/kg streptozotocin (STZ) solution. After continued feeding for 3 weeks, the rats were divided into normal group, model group, alachloramine group, blood stasis removing group, phlegm removing group and phlegm-blood stasis co-treatment group according to random number table method, with 6 rats in each group. Xiaoxianxiong Decoction (4.05 g/kg), Xuefu Zhuyu Decoction (7.02 g/kg), Didang Xianxiong Decoction (8.10 g/kg) were administered to the stomach respectively in the phlegm removing group, the blood stasis removing group and the phlegm-blood stasis co-treatment group. Alachloramine (3 mg/kg) was administered to the stomach by gavage in the alachloramine group. After 8 weeks, HE staining was used to observe the morphological changes of myocardial tissue in diabetic rats. Masson staining was used to observe the deposition of collagen fibers in the myocardial interstitium in rats. The expression of JNK1 protein was determined by immunohistochemistry. JNK1 mRNA, IRS1 mRNA and NLRP3 expression levels were detected by Real-time PCR. Western blot was used to detect the protein expressions of IRS-1, p-Akt and NLRP3.Results:The myocardial cells in the model group were disorganized, with hypertrophy, blurred texture, inflammatory infiltration of interstitium, increased collagen fibers, and focal necrosis. All treatment groups could improve fibrosis, inflammatory infiltration and reduce myocardial collagen deposition in different degrees. Compared with the model group, the mRNA and protein expressions of JNK1 and NLRP3 bodies decreased ( P<0.01), the IRS-1 mRNA and protein increased ( P<0.01), and p-Akt protein expression increased ( P<0.01). Conclusions:The phlegm and stasis co-treatment can effectively improve the cardiomyopathy of diabetes rats, and the effect is better than the phlegm-resolving method or the stasis resolving method alone. The mechanism may be related to the inhibition of JNK signaling pathway activation, reduce the expressions of JNK1 and NLRP3, and increase the IRS-1 and Akt.