Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1α signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction.

Objective: To investigate the effects of Linggui Zhugan Decoction on mitochondrial and oxidative damage in rats with chronic heart failure after myocardial infarction and the related mechanisms. Methods: Chronic heart failure after myocardial infarction was established by coronary artery ligation. Heart failure rats were randomly divided into three groups: Model group (n = 11), Linggui Zhugan Decoction group (n = 12), and captopril group (n = 11). Rats whose coronary arteries were only threaded and not ligated were sham group (n = 11). Cardiac function, superoxide dismutase (SOD), malondialdehyde (MDA) contents, soluble growth-stimulating expression factor (ST2), and N-terminal B-type brain natriuretic peptide precursor (NTproBNP) levels were analyzed after treatment. Moreover, the level of mitochondrial membrane potential was detected by JC-1 staining, the ultrastructural of myocardial mitochondria were observed by transmission electron microscopy. The related signal pathway of silent information regulator factor 2-related enzyme 1 (SIRT1), adenylate activated protein kinase (AMPK), phosphorylated adenylate activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is an important pathway to regulate mitochondrial energy metabolism, and to initiate mitochondrial biogenesis. The expression level was detected by Western blot and reverse transcription to explore the mechanism of the decoction. Results: Compared with the model rats, Linggui Zhugan Decoction significantly improved cardiac function (p < 0.05), reduced MDA production (p < 0.01), increased SOD activity (p < 0.05), reduced ST-2(p < 0.01), and NT-proBNP(p < 0.05) levels, increased mitochondrial membrane potential, and improved mitochondria function. In addition, Linggui Zhugan Decoction upregulated the expression of SIRT1, p-AMPK, PGC-1α protein, and mRNA in cardiac myocytes. Conclusion: Linggui Zhugan Decoction can improve the cardiac function of heart failure rats by enhancing myocardial antioxidant capacity and protecting the mitochondrial function, the mechanism is related to activating SIRT1/AMPK/PGC-1α signaling pathway.

Analysis of the Efficacy of Multidrug Combination Chemotherapy Regimens for Osteosarcoma and the Management of Chemotherapeutic Reactions.

Purpose: To analyse the efficacy of high-dose methotrexate + adriamycin + cisplatin (HD-MTX + ADR + PDD, MAP) regimens applied to osteosarcoma and the pretreatment and resolution of chemotherapeutic reactions. Methods: The clinical data of 21 patients with osteosarcoma in our hospital from January 2015 to January 2018 were retrospectively analysed. All patients were treated with the MAP protocol, 21 days for 1 cycle, and treated with artificial joint replacement or amputation after 3∼4 cycles of treatment. The tumour tissue necrosis rate, limb preservation success rate after treatment, and chemotherapy response during chemotherapy were counted and analysed for all patients. A local recurrence rate, a distant metastasis rate, and an overall survival rate were recorded during the 3-year follow-up period. Results: After treatment, the percentage of tumour tissue necrosis ≥90% was 85.71% (18/21) and the percentage of successful limb preservation was 57.14% (12/21) in 21 patients with osteosarcoma. During chemotherapy, all 21 patients with osteosarcoma experienced various degrees of chemotherapy reactions, mainly bone marrow suppression of 100% (21/21), gastrointestinal reactions of 100% (21/21), liver function impairment of 66.67% (14/21), and cardiotoxicity of 52.38% (11/21), all of which improved and completed treatment after treatment. During the 3-year follow-up period, the 21 patients with osteosarcoma had a local recurrence rate of 9.52% (2/21), a distant metastasis rate of 28.57% (6/21), and an overall survival rate of 80.95% (17/21). Conclusion: With stringent protection and relief measures, patients with osteosarcoma treated with the MAP regimen have promising near-term outcomes, with high survival rates over 3 years and tolerable chemotherapy responses. The clinical trial is registered under L2015093.

Acupuncture relieves motion sickness via the IRß-ERK1/2-dependent insulin receptor signalling pathway.

OBJECTIVE: Acupuncture has been widely used for the treatment of motion sickness (MS), but the underlying mechanisms are unclear. The aim of this research was to study the mechanism of acupuncture in the treatment of MS. METHODS: To observe the effects of acupuncture in the treatment of MS, 80 rats were randomised into five groups that were subjected to acceleration and either remained untreated (CTRL), or received restraint (REST), scopolamine (SCOP) or acupuncture at SP4 (sham) or PC6+ST36 (verum) acupuncture points. To study the mechanism underlying the effects of acupuncture in the treatment of MS, 48 rats were randomised into three groups: acupuncture+extracellular regulated protein kinases (ERK) 1/2 inhibitor (ERKinh), acupuncture+insulin receptor (IR) antagonist (IRant), and acupuncture+vehicle (VEH). After acceleration, the MS index (MSI) and spontaneous activity (SA) of the rats were recorded. Serum stress hormones, Fos-positive cells, c-fos mRNA in the vestibular nucleus, and IRß-, p-IRß-, ERK1/2- and p-ERK1/2-positive cells in the dorsal motor nucleus of the vagus nerve (DMV) were detected. RESULTS: After acceleration, MS symptoms in the PC6+ST36 and SCOP groups were reduced compared with the CTRL, REST, and SP4 groups. The number of p-IRß- and p-ERK1/2-positive cells and insulin levels were higher in the PC6+ST36 group than in the CTRL, REST, and SP4 groups. After ERK1/2 inhibitor and IR antagonist treatment, MS symptoms in the VEH group were lower than in the ERKinh and IRant groups. CONCLUSIONS: Our study demonstrates that acupuncture significantly alleviates MS through the IRß-ERK1/2-dependent insulin receptor signalling pathway in the DMV.