1.Regulatory Effect of Xiaoyaosan Combined with Pirfenidone on Idiopathic Pulmonary Fibrosis and Depression in Rats Based on p38 MAPK/NF-κB Inflammatory Pathway
Zilong CUI ; Bitao ZHANG ; Peijian FAN ; Yuanyuan LI ; Shaoxian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):1-11
ObjectiveTo observe the mechanism of chronic psychological stress aggravating idiopathic pulmonary fibrosis (IPF) in rats and the regulatory effect of Xiaoyaosan. MethodSixty SD rats were acclimatized for one week and then randomly divided into five groups: sham operation group, IPF group, IPF and depression model group, pirfenidone group, and pirfenidone + Xiaoyaosan group, with 12 rats in each group. The IPF group was induced by intratracheal instillation of bleomycin (5 mg·kg-1) and administered 0.9% sodium chloride solution intragastrically. The model group was induced with bleomycin (5 mg·kg-1) combined with chronic unpredictable mild stress to establish a rat model of IPF and depression and administered 0.9% sodium chloride solution intragastrically. Concurrently, the pirfenidone group was administered pirfenidone aqueous solution (50 mg·kg-1) intragastrically, and the pirfenidone + Xiaoyaosan group was administered pirfenidone aqueous solution (50 mg·kg-1) and Xiaoyaosan decoction (19.27 g·kg-1) intragastrically. The experiment lasted for four weeks. Various parameters, including body weight, food intake, sucrose consumption rate, open field behavior, lung function, lung coefficient, pathological changes in lung tissue, and hydroxyproline (HYP) content were compared among the groups. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum cortisol (CORT), corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) levels, and serotonin (5-HT) levels in serum and hippocampus. The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum and lung tissue were also measured. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA expression of IL-1β, TNF-α, IL-6, p38 mitogen-activated protein kinase (p38 MAPK), and nuclear transcription factor-κB p65 (NF-κB p65) in lung tissue. Western blot was used to detect the expression of proteins related to the p38 MAPK/NF-κB signaling pathway. ResultCompared with the normal group, IPF and depression model group showed slow weight gain, reduced food intake, decreased sucrose consumption rate, reduced total distance and average speed of movement in the open field test, weakened lung function, increased lung coefficient (P<0.01), significant inflammatory cell infiltration in lung tissue by hematoxylin-eosin (HE) staining, collagen fiber deposition by Masson staining, and increased HYP content (P<0.01). There were elevated levels of serum CORT, CRH, and ACTH (P<0.05, P<0.01), increased protein and mRNA levels of IL-1β, IL-6, and TNF-α in serum and lung tissue, decreased 5-HT levels in serum and hippocampus, and increased relative expression of p-p38 MAPK and p-NF-κB p65 proteins in lung tissue (P<0.01). Compared with the IPF and depression model group, the depression and IPF of rats in the pirfenidone + Xiaoyaosan group were effectively ameliorated, as evidenced by faster weight gain, increased food intake and sucrose consumption rate, increased total distance and average speed of movement in the open field test, enhanced lung function, reduced lung coefficient (P<0.01), decreased inflammatory cell infiltration by HE staining, reduced collagen fiber deposition by Masson staining in lung tissue, and decreased HYP content (P<0.01). Decreased serum CORT, CRH, and ACTH levels (P<0.05, P<0.01), decreased protein and mRNA levels of IL-1β, IL-6, and TNF-α in serum and lung tissue (P<0.05, P<0.01), increased 5-HT levels in serum and hippocampus (P<0.05, P<0.01), and decreased relative expression of p-p38 MAPK and p-NF-κB p65 proteins in lung tissue were also noted (P<0.05, P<0.01), with the effects of Xiaoyaosan + pirfenidone being more significant. ConclusionChronic unpredictable stress exacerbates the progression of IPF in rats. The combination of Xiaoyaosan and pirfenidone not only improves depressive-like behavior but also alleviates pulmonary fibrosis, potentially through the regulation of the p38 MAPK/NF-κB signaling pathway and inhibition of excessive expression of inflammatory factors.
2.A Survey of the Current Status of Surgical Treatment of Hemophilic Osteoarthropathy in China Mainland 17 Grade A General Hospitals
Yiming XU ; Huiming PENG ; Shuaijie LYU ; Peijian TONG ; Hu LI ; Fenyong CHEN ; Haibin WANG ; Qi YANG ; Bin CHEN ; Zhen YUAN ; Rongxiu BI ; Jianmin FENG ; Wenxue JIANG ; Zongke ZHOU ; Meng FAN ; Xiang LI ; Guanghua LEI ; Xisheng WENG
JOURNAL OF RARE DISEASES 2023;2(4):516-522
3.Intra-articular injection of autologous adipose-derived stem cells for knee osteoarthritis: a randomized controlled trial
Shengyang ZHANG ; Shuaijie LYU ; Quanwei DING ; Mengqiang FAN ; Peijian TONG
Chinese Journal of Orthopaedics 2018;38(23):1426-1434
Objective To evaluate the clinical effects of intra-articular injection of autologous adipose derived stem cells (ADSCs) or ADSCs combined with hyaluronate acid (HA) for knee osteoarthritis.Methods From May 2013 to May 2015,a total of 108 patients with knee osteoarthritis (Kellgren-Lawrence grades:1-3) were recruited in the present study.The patients were randomly divided into three groups:ADSCs,HA and ADSCs+HA.All patients (36 cases in each group) were injected with the drug in the joint cavity once a week for three weeks.The methods used for evaluating the clinical manifestations and joint damage on MRI included visual analogue scale (VAS),Western Ontario and McMaster University (WOMAC) osteoarthritis index and whole-organ magnetic resonance imaging score (WORMS).Evaluations were conducted before injection and at 3,6,12,24 and 36 months after injection.Results All patients were followed up for 36 months without any dissociation.No adverse reaction was observed during the treatment and at the follow-up duration.The VAS score and WOMAC total score of the ADSCs group and the ADSCs+HA group were better than those in the HA group at each time point after injection (P<0.05).The average VAS of the ADSCs group decreased from 4.14±1.42 at pre-injection to 2.39±1.74 at 36 months after injection.The WOMAC total score decreased from 42.86± 31.24 to 27.17±27.99.The average VAS in the ADSCs+HA group decreased from 4.25±1.13 to 2.31±1.74,and the WOMAC total score decreased from 34.92±22.62 to 21.33±21.38.However,the average VAS and WOMAC total score of the HA group at 36 months after injection were higher than those before the injection.In terms of the VAS at 3 months after injection,the ADSCs+HA group scored better than that of the ADSCs group (P<0.05).There was no significant difference in WOMAC scores between the ADSCs and ADSCs+HA groups at each time point after injection (P>0.05).The WORMS cartilage injury score improved in 10 patients with ADSCs after injection (P<0.05).The subchondral bone wear score improved as well (P<0.05).The difference of WORMS cartilage injury scores before and after injection was correlated with the difference of the WOMAC total score (r=0.790,P=0.007) and that of VAS score difference (r=0.800,P=0.005).Conclusion Autologous ADSCs and ADSCs combined with HA intra-articular injections can effectively relieve pain and improve function of patients with knee osteoarthritis for 36 months.In addition,ADSCs combined with HA injections can relieve pain more effectively within a short duration.Cartilage repair is associated with joint function improvement.

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