1.Erk Signaling Pathway in Striatal D2-MSNs: an Essential Pathway for Exercise-induced Improvement in Parkinson’s Disease
Bo GAO ; Yi-Ning LAI ; Yi-Tong GE ; Wei CHEN
Progress in Biochemistry and Biophysics 2025;52(1):61-71
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D1-dopamine receptor (D1R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D2-dopamine receptor (D2R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D1R and D2R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.
2.Chinese expert consensus on postoperative follow-up for non-small cell lung cancer (version 2025)
Lunxu LIU ; Shugeng GAO ; Jianxing HE ; Jian HU ; Di GE ; Hecheng LI ; Mingqiang KANG ; Fengwei TAN ; Fan YANG ; Qiang PU ; Kaican CAI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(03):281-290
Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.
3.Treatment of Neurological Diseases with Chaihu Guizhi Ganjiangtang: A Review
Ge HAO ; Changyu GAO ; Zexin PAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):313-322
Neurological diseases encompass a wide range of conditions, and their incidence and mortality rates have been increasing year by year, severely endangering the health and lives of patients. Chaihu Guizhi Ganjiangtang is a recognized prescription formulated by ZHANG Zhongjing, which has a wide application in clinical practices. It exerts the effects of harmonizing and releasing Shaoyang, warming the spleen to dispel cold, and producing fluid and astringing Yin. Clinical studies have confirmed that Chaihu Guizhi Ganjiangtang, with modified herbs or in combination with acupuncture, moxibustion, or Western medicine, exhibits remarkable efficacy, minimal adverse reactions, and high safety in the treatment of neurological diseases such as insomnia, depression, anxiety disorders, dizziness, headache, perimenopausal syndrome (PMS), diabetic peripheral neuropathy (DPN), post-stroke restless legs syndrome (RLS), bipolar disorders, and tic disorders in children. Modern pharmacological studies have pointed out that the main active ingredients of single herbs in the whole formula and composition of Chaihu Guizhi Ganjiangtang, such as saikosaponins, estradiol, cinnamaldehyde, baicalin, oroxindin, gingerol, 6-shogaol, glycyrrhizic acid, and liquiritin, can exert multi-target and multi-pathway effects, including reducing oxidative stress, alleviating neuroinflammation, inhibiting ferroptosis, microglial cell activation, and neuroapoptosis, and regulating neurotransmitter levels, estrogen levels, synaptic plasticity, neuronal autophagy level, and gluconeogenic metabolism. By reviewing relevant literature in recent years, this article summarized the clinical research and mechanism of action of Chaihu Guizhi Ganjiangtang in the treatment of neurological diseases and put forward corresponding suggestions, providing references for in-depth research.
4.Research progress in the effect of estrogen on tendinopathy
Qingfeng SUN ; Shuo BAI ; Zhen ZHANG ; Liang SHEN ; Beiyao GAO ; Ruidong GE
Chinese Journal of Tissue Engineering Research 2024;28(32):5231-5237
BACKGROUND:Increasing studies have found that estrogen has a certain correlation with tendinopathy,but for a long time,there are few experiments and summaries of estrogen in tendinopathy,which makes it difficult for specialists and scholars in related fields to fully understand the research status. OBJECTIVE:To summarize the current clinical or preclinical original research,so as to summarize the role of estrogen in tendinosis,and make a certain prospect for the evaluation and management of estrogen in tendinosis in the future. METHODS:Relevant literature in PubMed,Web of Science,CNKI,WanFang,and VIP databases were searched by computer.Search time was from January 2008 to September 2023.The search terms were"oestrogen,estrogen,estrogen receptor,tendinopathy,tendonopathy,sinew,tendon,tendons,myotenositis"in English and"estrogen,estrogen receptor,tendinosis,tendon,tendinitis"in Chinese.According to the selection criteria,the search results were screened and excluded,and finally 60 documents were included for review and analysis. RESULTS AND CONCLUSION:In vivo studies have shown that estrogen can promote tendon anabolism.In vitro experiments have also proved that various estrogens can promote the proliferation of tendon cells and reduce inflammation and apoptosis,but most of the experiments are limited to animal models.Estrogen receptor β acts more in tendon injury and repair processes,but estrogen receptor α has not been found to have a major impact on tendon injury.The expression of estrogen receptor β can repair the tendon by affecting the formation of fat,the deposition of type I collagen and reducing the apoptosis of tendon cells,while its over-expression may promote inflammation and angiogenesis,thus promoting the inflammatory process and playing a role in tendon injury.Animal studies have shown that estrogen deficiency may reduce the synthesis efficiency of collagen in the tendon,decrease the elasticity of tendon,inhibit the synthesis and metabolism of the tendon,which is not conducive to the repair of tendon injury,while normal level of estrogen may stimulate the synthesis of type I collagen in tendon and promote the proliferation and metabolism of tendon cells.At present,the molecular mechanism of estrogen in tendon injury has not been fully explained.More experiments focus on tendon collagen synthesis,cell proliferation and apoptosis.Only a few documents have studied the molecular mechanisms of estrogen receptor β deficiency regulating interferon regulatory factor 5-chemokine ligand 3 axis,E2 regulating estrogen receptor α and PI-3K-Akt signaling pathways,and high levels of estradiol reducing the level of free-circulating insulin-like growth factor.Various estrogens,including endogenous estrogens and phytoestrogens,are beneficial to the repair of tendinopathy at normal levels,and estrogen receptor β mainly affects the formation of fat,the deposition of type I collagen and the reduction of apoptosis of tendon cells through,which lays a foundation for the future treatment of tendinopathy with different subtypes of estrogens in vivo and the influence of estrogen membrane receptors on tendinopathy.
5.Energy metabolism, immune function, and intestinal flora in rats with kidney-yin deficiency treated with raw or saltwater-processed Phellodendron chinense Schneid
Wenjing Ren ; Jiahui Zhao ; Li Li ; Xiutong Ge ; Yue Zhou ; Yang Chen ; Shiru Jiang ; Tianzhu Jia ; Hui Gao ; Fan Zhang
Journal of Traditional Chinese Medical Sciences 2024;11(4):488-499
Objective:
To clarify the specific mechanisms of action of raw Phellodendron chinense Schneid. (RPC) and saltwater-processed PC (SPC) in the treatment of rats with a kidney-yin deficiency pattern (KYDP).
Methods:
Healthy rats were administered hydrocortisone to establish a KYDP model. The rats were divided into seven groups: blank control, model, positive control (Liuwei Dihuang pills), high-dose RPC, low-dose RPC, high-dose SPC, and low-dose SPC. Enzyme-linked immunosorbent assay was used to measure the levels of cAMP, cGMP, TRH, TSH, T3, T4, IFN-γ, TNF-α, and testosterone in the serum and the levels of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in the liver. TRH mRNA expression in the rat hypothalamus was measured using RT-PCR. THRα1+2 protein expression in the hypothalamus of rats was measured using Western blot. Immunohistochemistry was performed to determine the expression levels of FAS, FasL, and TSHR. Flow cytometry was used to determine CD4+ and CD8+ T lymphocyte levels. Illumina MiSeq sequencing technology was used to evaluate the diversity of intestinal flora in KYDP rats.
Results:
The cAMP/cGMP ratio was significantly higher in the model group than in the blank control group (P = .048). Compared with the model group, after administration, the levels of the above-mentioned serum and liver indexes decreased, except that of testosterone. The CD4+/CD8+ ratio also decreased. Compared with the RPC group, the levels of T3, IFN-γ, FAS, FasL, and TSHR in the SPC group decreased whereas that of testosterone increased. Additionally, immune function and intestinal flora diversity improved in the SPC group. SPC proved to be more effective in improving liver energy metabolism in KYDP rats than RPC.
Conclusion
SPC had a better therapeutic effect on KYDP than RPC. The underlying mechanism of action may be related to improvements in liver energy metabolism, immune function, and intestinal flora diversity.
6.Safety and strategy of intravascular intervention in ruptured intracranial vertebral artery dissecting aneurysm
Hao ZHU ; Yingang WU ; Hao CUI ; Jian YU ; Yu CHEN ; Daqun GU ; Yang ZHANG ; Chaoshi NIU ; Ge GAO
Chinese Journal of Neuromedicine 2024;23(2):164-168
Objective:To investigate the safety and efficacy of intravascular intervention in ruptured intracranial vertebral artery dissecting aneurysm (IVADA).Methods:A retrospective analysis was performed; 25 patients with ruptured IVADA (25 aneurysms) admitted to Department of Neurosurgery, First Affiliated Hospital of University of Science and Technology of China from January 2020 to June 2023, were chosen. Aneurysm and parent artery occlusion or stent-assisted spring coil embolization were performed according to location of the aneurysms, degrees of aneurysm immediate embolization were evaluated by Raymond grading, and perioperative adverse events were recorded. The patients were followed up for 6-48 months, and aneurysm recurrence was determined according to DSA results; prognoses were assessed by modified Rankin Scale (mRS), with scores of 0-2 as good prognosis and scores of 3-6 as poor prognosis.Results:All 25 patients had unilateral ruptured IVADA, 10 (40%) received aneurysm and parent artery occlusion (occlusion of dissection segment) and 15 (60%) received stent-assisted embolization. Immediately after surgery, 19 patients (76%) had grading I embolization, 4 (16%) grading II embolization, and 2 (8%) grading III embolization. No aneurysm rupture or stent related thrombosis was observed during procedure; 3 patients (12%) died after procedure, with postoperative rebleeding in 1, postoperative cerebellar infarction with respiratory failure in 1, and severe pneumonia in 1. In the 22 survivals, 18 had good prognosis and 4 had poor prognosis. In the 5 relapsed patients (all accepted stent-assisted embolization), 4 underwent re-intervention, and one with visualization at aneurysm neck was relatively stable on re-examination and accepted regular follow up.Conclusion:Aneurysm and parent artery occlusion can be used for non-dominant vertebral artery aneurysms not involving posterior inferior cerebellar artery, whose recurrence rate is lower than that of stent-assisted coil embolization.
7.Correlation between remnant cholesterol and anterior ischemic optic neuropathy
Qinglin FAN ; Yingjun LUN ; Renqing TAI ; Yao GE ; Hongcheng GAO ; Chen CHEN
International Eye Science 2024;24(8):1328-1331
AIM: To explore the correlation between remnant cholesterol(RC)and anterior ischemic optic neuropathy(AION).METHODS: A total of 80 cases of AION patients hospitalized in the department of ophthalmology of Linyi People's Hospital from January 2020 to December 2023 were selected as the observation group, and 80 cases of those who had completed health checkups in Linyi People's Hospital during the same period(without ischemic optic neuropathy and other fundus vasculopathies)were selected as the control group. The general data and biochemical indexes of the two groups were compared to evaluate the correlation between RC and AION.RESULTS: Compared with the control group, the levels of RC, fasting blood glucose(FBG), triglyceride(TG), total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C)in patients with AION were significantly higher than those in the control group(all P<0.01). Spearman correlation analysis showed that RC was positively correlated with TG, TC, and LDL-C(all P<0.01). Logistic regression analysis showed that RC and FBG were risk factors for the development of AION. The analysis of receiver operating characteristic(ROC)curves showed that the level of RC had a better predictive value for the development of AION compared with FBG.CONCLUSION: RC is associated with the development of AION and is a risk factor for the development of AION. Clinical standardization of the management of people with high RC values can reduce the risk of the development of AION, which is of clinical significance.
8.Phosphatidylinositol 3-kinases Play a Suppressive Role in Electrotaxis of Dictyostelium Cells Through Akt and ERK
Xiao-Xue GE ; Rui-Da JIANG ; Xiao-Yan WANG ; Jing GAO ; Run-Chi GAO
Progress in Biochemistry and Biophysics 2024;51(3):685-695
ObjectivePhosphatidylinositol 3 kinases (PI3Ks) play an important role in cell directional movement by regulating F-actin. However, the structure and function of PI3Ks are complex. The role of PI3Ks in cell electrotaxis is not fully understood. Therefore, in this study, the model organism Dictyostelium discoideum cells were used as experimental materials to explore the role of PI3K1 and PI3K2 in electrotaxis. MethodsFirstly, PI3K1 coding gene pikA knockout mutant and PI3K2 coding gene pikB knockout mutant were constructed by CRISPR/Cas9 system. Secondly, two mutants were placed in a DC electric field with a strength of 12 V/cm and the electrotaxis were analyzed. ResultsData analysis showed that the direction index of wild-type cells in DC electric field was (0.86±0.03), while the direction index of pikA- and pikB- mutants in DC electric field was (0.95±0.02) and (0.94±0.03), respectively. In addition, the average trajectory speed of wild-type cells in the electric field was (3.34±0.08) μm/min, while the average trajectory speed of pikA- and pikB- mutants were (4.85±0.20) μm/min and (5.48±0.15) μm/min, respectively. The t test showed that there were significant differences in the directedness index and speed between the mutant and wild type. Western blot results showed that both phosphorylated Akt and phosphorylated ERK were significantly increased in pikA- and pikB- mutants. ConclusionPI3K1 and PI3K2 may inhibit the electrotaxis of Dictyostelium discoideum cells by increasing the activity of Akt and ERK.
9.Research progress on the function of ectopic olfactory receptors and their value as drug targets
Chang LIU ; Yongxin ZHAO ; Beibei GE ; Bin WEI ; Yong GAO
Journal of China Pharmaceutical University 2024;55(3):412-419
Olfactory receptors(ORs)are transmembrane proteins mainly distributed in olfactory sensory neurons of the nasal epithelium,mediating the transmission of real-time sensory signals to the brain to produce smell.Recent studies have reported that ORs can also be expressed in tissues or organs outside the nasal cavity,and are closely related to a variety of biological processes,such as sperm chemotaxis,wound healing,glycolipid metabolism and intestinal secretion.In addition,ORs are closely related to a variety of malignant tumors such as prostate cancer,breast cancer and colorectal cancer,and may affect the occurrence and development of tumors by regulating cell proliferation,apoptosis,migration and invasion.This review provides an overview of the effects of ectopic ORs on the function of various human tissues and organs and assesses their potential value as drug targets for the treatment of human diseases.
10.Curative effect of different types of stents treating vertebrobasilar dissection aneurysms
Yang Wang ; Xiaoyu Sun ; Jiajia Xu ; Yu Jian ; Yingjiu Chao ; Ge Gao
Acta Universitatis Medicinalis Anhui 2024;59(12):2190-2197
Objective:
To analyze the safety and effectiveness of different types of stents with the treatment of vertebraebasilar artery dissection aneurysms(VBADA).
Methods :
The clinical data of 80 patients with VBADA treated by intravascular intervention in the First Hospital of University of Science and Technology of China(Anhui Provincial Hospital) from February 2018 to November 2023 were retrospectively analyzed. Patients were divided into laser engraved stent group(n=34) and braided stent group(n=46) based on the type of stent used. O′Kelly-Marotta(OKM) grade was used to evaluate the embolization effect of aneurysms in DSA images, and a modified Rankin Scale(mRS) score was used to evaluate the clinical prognosis of patients. The baseline data, aneurysm characteristics, intraoperative and perioperative treatment details and postoperative follow-up details between the two groups were compared.
Results :
There was no significant difference in baseline data, mRS score, ischemic and hemorrhage complications and mortality between the two groups(allP>0.05). Compared with the laser engraved stent group, the mean diameter of aneurysms was larger(P<0.000 1) and the proportion of ruptured aneurysm(P<0.01), parent artery stenosis and beaded vascular lesions(P<0.05) and branch artery dissecting aneurysm were higher(P<0.01) in the braided stent group. Conversely, the proportion of coil-assisted embolization(P<0.000 1) and the immediate aneurysm occlusion rate(OKM C and D)(P<0.000 1) were lower. Finally, 21 patients were obtained by controlling for maximum diameter of aneurysms and whether coil-assisted embolization, the aneurysm occlusion rate half a year later in the braided stent group was higher than that in the laser engraved stent group(P<0.05), but the recurrence rate of postoperative aneurysm was lower than that of laser engraved stent group(P<0.05). It was worth noting that the cure rate and vascular remodeling rate of middle-large size VBADA which the maximum diameter being over 15 mm in the braided stent group reached 72.2%, and the whole effect was ideal.
Conclusion
Braided stents are relatively safe and effective in the treatment of VBADA and are significantly better than laser engraved stents in reducing VBADA recurrence and remodeling lesion vessels without increasing postoperative complication.


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