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Min-Jie Wang,1– 3 Jiayu Wang,4 Houdi Zhang,2,3 Fang-Bin Hao,1– 3 Gan Gao,1– 3 Si-Meng Liu,1– 3 Xiao-Peng Wang,1– 3 Jing-Jie Li,1– 3 Zheng-Xing Zou,2,3 Qing-Bao Guo,1– 3 He-Guan Fu,2,3 Yi-Qin Han,2,3 Cong Han,2,3 Lian Duan2,3 1Chinese PLA Medical School, Beijing, People’s Republic of China; 2Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Neurosurgery, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lian Duan; Cong Han, Department of Neurosurgery, Department of Neurosurgery, the Fifth Medical Centre (South Campus), Chinese PLA General Hospital, No. 8 Dong-Da Street, Fengtai District, Beijing, 100071, People’s Republic of China, Tel +86-10-66947389 ; +86-13466346163 ; +86-10-66947388, Fax +86-10-62177976, Email duanlian307@sina.com; hc82225@126.comBackground: The immune system plays an important role in the onset and development of moyamoya disease (MMD), but the specific mechanisms remain unclear. This study aimed to explore the relationship between the expression of complements and immunoglobulin in serum and progression of MMD.Methods: A total of 84 patients with MMD and 70 healthy individuals were enrolled. Serum immunoglobulin and complement C3 and C4 expression were compared between healthy individuals and MMD patients. Follow-up was performed at least 6 months post-operation. Univariate and multivariate analysis after adjusting different covariates were performed to explore predictive factors associated with vasculopathy progression. A nomogram basing on the results of multivariate analysis was established to predict vasculopathy progression.Results: Compared to healthy individuals, MMD patients had significantly lower expression of serum complements C3 (P = 0.003*). Among MMD patients, C3 was significantly lower in those with late-stage disease (P = 0.001*). Of 84 patients, 27/84 (32.1%) patients presented with vasculopathy progression within a median follow-up time of 13.0 months. Age (P=0.006*), diastolic blood pressure (P=0.004*) and serum complement C3 expression (P=0.015*) were associated with vasculopathy progression after adjusting different covariables.Conclusion: Complement C3 is downregulated in moyamoya disease and decreases even further in late–Suzuki stage disease. Age, diastolic blood pressure and serum complement C3 expression are associated with vasculopathy progression, suggesting that the complement might be involved in the development of moyamoya disease.Keywords: moyamoya disease, complement, Suzuki stage, nomogram

Li Chen,1 Wang-Yang Xu,2 Hao Chen,1 Yan-Quan Han,1 Yu-Ting Zhang1 1The First Affiliated Hospital, Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of China; 2The College of Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of ChinaCorrespondence: Hao Chen; Yanquan Han, The First Affiliated Hospital, Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of China, Email chenhao071522@163.com; hyquan2003@163.comPurpose: Gandouling Tablets (GDL), a proprietary Chinese medicine, have shown a preventive effect against Wilson’s disease (WD)-induced neuronal damage in previous studies. However, the potential mechanisms need additional investigation. Combining metabonomics and network pharmacology revealed the GDL pathway against WD-induced neuronal damage.Methods: The WD rat model with a high copper load was developed, and nerve damage was assessed. Total metabonomics was used to identify distinct hippocampus metabolites and enriched metabolic pathways in MetaboAnalyst. The GDL’s possible targets against WD neuron damage were then determined by network pharmacology. Cytoscape constructed compound metabonomics and pharmacology networks. Moreover, molecular docking and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) validated key targets.Results: GDL reduced WD-induced neuronal injury. Twenty-nine GDL-induced metabolites may protect against WD neuron injury. According to network pharmacology, we identified three essential gene clusters, of which genes in cluster 2 had the most significant impact on the metabolic pathway. A comprehensive investigation identified six crucial targets, including UGT1A1, CYP3A4, CYP2E1, CYP1A2, PIK3CB, and LPL, and their associated core metabolites and processes. Four targets reacted strongly with GDL active components. GDL therapy improved five targets’ expression.Conclusion: This collaborative effort revealed the mechanisms of GDL against WD neuron damage and a way to investigate the potential pharmacological mechanisms of other Traditional Chinese Medicine (TCM).Graphical Abstract: Keywords: GDL, metabonomics, network pharmacology, mechanisms

LingYu Pan,1,* YanQuan Han,1,* YongZhong Wang,1 QianQian Chen,2 Ying Wu,2 Yuan Sun2 1Grade 3 Preparation Laboratory of State Administration of TCM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; 2Anhui University of Chinese Medicine, Hefei, Anhui 230031, China *These authors contributed equally to this work Purpose: Yanghe Pingchuan granules (YPG), a hospital preparation developed by The First Affiliated Hospital, Anhui University of Chinese Medicine, has been used for the clinical treatment of bronchial asthma (BA) for several decades. This study aimed to explore the mechanism of action of YPG in the treatment of BA. Materials and methods: Male Sprague Dawley rats (n=60) were randomly divided into six groups (n=10 per group): control, a BA model, positive drug control (Guilong Kechuanning capsules; a proven effective treatment for BA), and model rats treated with a high, medium, or low dose of YPG. H&E staining was used to detect pathological changes in the bronchial tubes. The mRNA expression levels of PI3K, PKB, PCNA, and AR were determined by real-time PCR, and the protein levels of phospho- (p-)PI3K, p-PKB, p-PCNA, and p-AR were detected by Western blotting. ELISAs were used to detect the expression of PIP2, PIP3 IL-6, IL-8, IL-1β, and epinephrine (EPI). Results: H&E staining demonstrated that BA can be ameliorated using YPG. Real-time PCR, Western blotting, and ELISA indicated that use of YPG decreased expression of the phosphoinositide 3-kinase (PI3K) signaling pathway and PCNA, and can also ameliorate the condition kidney Yang deficiency, which is associated with BA in Chinese traditional medicine. Conclusion: YPG can attenuate BA therapeutically in a dose-dependent manner. The mechanism underlying its therapeutic effect comprises influences on three features that contribute to BA: the PI3K signaling pathway, cell proliferation, and “kidney-Yang deficiency”. Keywords: bronchial asthma, YPG, PI3K/PKB signaling pathway, cell proliferation, kidney Yang deficiency