[Clinical effect of the warm acupuncture of Mongolian medicine on insomnia in the elderly and its brain-gut peptide mechanism: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect and safety of the warm acupuncture of Mongolian medicine in treatment of insomnia in the elderly, and to explore its underlying brain-gut peptide mechanism. METHODS: Sixty elderly patients with insomnia were randomly divided into a warm acupuncture group and a western medication group, 30 cases in each group. In the warm acupuncture group, the warm acupuncture of Mongolian medicine was operated at Dinghuixue (at the center of the vertex, the crossing site of the anterior midline and the line connected the upper edges of two ear apexes), Heyixue (at the depression of the spinous process of the 7th cervical vertebra) or Xinxue (at the depression of the spinous process of the 6th thoracic vertebra) in each treatment. Only one of the above points was selected and stimulated for 20 min one treatment and the three points were used alternatively. The treatment was given once every day or every other day, 3 times a week, and for a total of 3 weeks. In the western medication group, estazolam tablets were administered orally, once a day, 1 mg before bedtime, consecutively for 3 weeks. Before and after treatment, as well as in 1-month follow-up visit after the treatment completion, the scores of the Pittsburgh sleep quality index (PSQI) and the insomnia severity index (ISI) were observed in the two groups. The serum brain-related peptide markers (substance P [SP], neuropeptide Y [NPY], 5-hydroxytryptamine 1A [5-HT1A] and 5-hydroxytryptamine 2A [5-HT2A]) were measured before and after treatment, and the clinical efficacy and safety was evaluated in the two groups. RESULTS: After treatment and in follow-up, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance and daytime dysfunction, as well as the total scores of PSQI, and ISI scores were all reduced in the two groups (P<0.05, P<0.01); and the scores in the warm acupuncture group were lower than those of the western medication group (P<0.05, P<0.01). After treatment, the levels of serum SP and 5-HT2A were decreased (P<0.01) and the levels of serum NPY and 5-HT1A were increased (P<0.01) when compared with those before treatment in the two groups. The levels of serum SP and 5-HT2A in the warm acupuncture group were lower than those of the western medication group (P<0.05), and the levels of serum NPY and 5-HT1A were higher than those of the western medication group (P<0.05). After treatment, the total effective rate was 93.3% (28/30) in the warm acupuncture group, which was higher than 83.3% (25/30) of the western medication group (P<0.05). No serious adverse reactions were found in the two groups. CONCLUSION: Warm acupuncture of Mongolian medicine can effectively improve the sleep quality of the elderly patients with insomnia, and its mechanism may be related to the regulation of the levels of serum SP, NPY, 5-HT1A and 5-HT2A.

Dracocephalum moldavica L. extract alleviates experimental colitis in rats by modulating gut microbiome and inflammatory pathways.

Several studies have revealed that an imbalance of the intestinal microbiota is involved in intestinal inflammation associated with ulcerative colitis (UC). Therefore, regulating the homeostasis of gut microbiota is critical for treating UC. Dracocephalum moldavica L. (DML) extract, a common traditional Chinese medicine, has been demonstrated to possess numerous pharmacological effects, such as antioxidative, anti­inflammatory, and antibacterial properties. The aim of the present study was to evaluate the beneficial effects of DML extract and the probable mechanism of action in a dextran sulfate sodium­induced chronic colitis model. It was found that DML extract ameliorated UC by improving disease activity index, weight loss, colon length, and histological scoring. DML extract administration also enhanced the count of Lactobacillus and reduced the count of Romboutsia. Furthermore, the results of network pharmacology analysis revealed that the active ingredients (including luteolin, rosmarinic acid, oleanolic acid, ursolic acid, apigenin, acacetin, kaempferol, and isorhamnetin) in the DML extract were closely associated with anti­inflammatory activity via various signaling pathways, including the NF­κB, IL­17, TNF, and Toll­like receptor (TLR) signaling pathways. Western blot analysis further indicated that DML extract downregulated the expression of members of the TLR4/NF­κB signaling pathway, which was associated with colitis. Thus, it was hypothesized that DML extract exerted its anti­colitis effects by modulating the gut microbiota and inflammatory pathways.

Study on the clinical efficacy of Mongolian medicine in the treatment of osteoarthritis.

OBJECTIVE: The object of this paper was to evaluate the clinical efficacy and safety of Mongolian medicine in the treatment of osteoarthritis (OA). This was completed by offering evidence to provide a clinical basis for the treatment of OA. We explored the mechanism of the sticking application of Mongolian medicine. METHOD: A total of 123 patients with OA diagnosed in the Affiliated Hospital of Inner Mongolia Medical University from January 2017 to December 2017 were enrolled. The clinical data of the patients were retrospectively analyzed. Patients were divided into three groups according to the medication they were using at the time: The strapping group, the glucosamine hydrochloride group, and the Mongolian medicine group, with 41 patients in each group. The treatment indicators of the included patients 2 weeks after the treatment and 4 weeks after the treatment were fully recorded in our hospital. The levels of CGRP, TNF-α, MMP-3, VEGF, and IL-10 before and after treatment were measured by ELISA. The auxiliary diagnostic index was X-ray film. RESULTS: Compared with the control group, the Mongolian medicine group improved the symptoms of pain, swelling, limited movement, and daily life quality of patients to different degrees. There was a significant decrease in the VAS score at each time point of the Mongolian medicine group (P < 0.05). tThe scores of bodily pain in SF-36 QOL were significantly higher in the Mongolian medicine group at different time points (P < 0.05). After treatment, the levels of MMP-3, TNF-α, VEGF, and CGRP in the Mongolian medicine group were significantly lower than those before the treatment (P < 0.05). CONCLUSION: Mongolian medicine can inhibit the expression of MMP-3, TNF-α, VEGF, and CGRP in serum, and up-regulate the trend of IL-10, alleviating the inflammatory reaction. It has a good curative effect in the treatment of OA patients. It is better than western medicine in pain, swelling, and improving bone and joint function index.

[Analysis on formula of Mongolian medicine for prevention of COVID-19].

The epidemic situation of coronavirus disease 2019(COVID-19) is developing rapidly in the world, and the influence is serious. In this study, the prescription of Mongolian medicine to prevent new type of COVID-19 was investigated. Based on the second edition and the third edition of COVID-19 Mongolian Medicine Prevention and Treatment Guidance Program issued by the Inner Mongolia Autonomous Region Health Commission, using Excel 2007, SPSS Modeler 18, SPSS Statistics 25, Cytoscape 3.7.1 statistical software as a tool, the association rules analysis and cluster analysis of Mongolian medicine included in the standard were carried out. Among the 45 prophylactic prescriptions included in the standard, a total of 34 high-frequency drugs using frequency ≥5 were used, of which Carthami Flos(21 times, 4.46%), Chebulae Fructus(20 times, 4.26%), Moschus(13 times, 2.77%), Myristicae Semen(12 times, 2.55%), Santali Albi Lignum(12 times, 2.55%), and Bovis Calculus(12 times, 2.55%) were the most common. The main drugs for the prevention of COVID-19 were Liang(13 times, 38.23%), Wen(9 times, 26.47%), the flavor was Ku(20 times, 34.48%), Xin(13 times, 22.41%), Gan(11 times, 18.97%), the most used drugs treating hot evil(99 times, 32.46%), treatment of "Heyi" drugs(51 times, 16.72%), treatment of "Badagan" drugs(40 times, 13.11%), treatment of "sticky" drugs(37 times, 12.13%), and a cough, eliminating phlegm and antiasthmatic(31 times, 10.16%), the association rule analysis found that the highest association intensity of the drug pair combination of 11. Clustering analysis using the cluster analysis of inter-group join method found a total of 8 categories. In this study, 45 prescriptions of Mongolian medicine for the prevention of COVID-19 were collec-ted and further analyzed, hoping to provide new ideas for clinical diagnosis and treatment.

iTRAQ-based proteomics analysis on insomnia rats treated with Mongolian medical warm acupuncture.

OBJECTIVE: To explore the proteomic changes in the hypothalamus of rats treated with Mongolian medical warm acupuncture for insomnia therapy based proteomics. METHOD: We used an iTRAQ-based quantitative proteomic approach to identify proteins that potential molecular mechanisms involved in the treatment of insomnia by Mongolian medical warm acupuncture. RESULT: In total, 7477 proteins were identified, of which 36 proteins showed increased levels and 45 proteins showed decreased levels in insomnia model group (M) compared with healthy control group (C), 72 proteins showed increased levels and 44 proteins showed decreased levels from the warm acupuncture treated insomnia group (W) compared with healthy controls (C), 28 proteins showed increased levels and 17 proteins showed decreased levels from the warm acupuncture-treated insomnia group (W) compared with insomnia model group (M). Compared with healthy control groups, warm acupuncture-treated insomnia group showed obvious recovered. Bioinformatics analysis indicated that up-regulation of neuroactive ligand-receptor interaction and oxytocin signaling was the most significantly elevated regulate process of Mongolian medical warm acupuncture treatment for insomnia. Proteins showed that increased/decreased expression in the warm acupuncture-treated insomnia group included Prolargin (PRELP), NMDA receptor synaptonuclear-signaling and neuronal migration factor (NSMF), Transmembrane protein 41B (TMEM41B) and Microtubule-associated protein 1B (MAP1B) to adjust insomnia. CONCLUSION: A combination of findings in the present study suggest that warm acupuncture treatment is efficacious in improving sleep by regulating the protein expression process in an experimental rat model and may be of potential benefit in treating insomnia patients with the added advantage with no adverse effects.

Effect of Mongolian warm acupuncture on the gene expression profile of rats with insomnia.

BACKGROUND: The mechanism of Mongolian warm acupuncture (MWA) for the treatment of insomnia has not been previously reported. OBJECTIVE: To investigate the effect of MWA on gene expression profile in the p-chlorophenylalanine (PCPA)-induced rat model of insomnia. METHODS: A rat model of insomnia was established and the animals were divided into five groups: control, PCPA (untreated), PCPA+estazolam, PCPA+MA (manual acupuncture), and PCPA+MWA. The rats were euthanased at 7 days after treatment, and hypothalamic tissue was harvested to extract total RNA for the analysis of gene expression profile. Micro-array and Partek Genomics Suite analysis system were used to analyse differential expression of genes between groups. Furthermore, ingenuity pathways analysis was used to analyse the main regulators. RESULTS: After treatment, in rats with improved sleep, micro-array data from the follow-up phase compared with baseline showed that MWA down-regulated 11 genes compared with the control group and 16 genes compared with the PCPA group. Six genes were selected following the micro-array detection to perform quantitative polymerase chain reaction (qPCR) verification, and the results showed that the coincidence rate was up to 90%, which verified the reliability of the microarray results. Compared with the PCPA group, transcription levels of Egr 1, Btg2 and BDNF in the PCPA+MWA group were up-regulated (P<0.05). CONCLUSION: In combination, the findings of this study suggests that MWA is efficacious at improving sleep in an experimental rat model of insomnia.

Effects of Mongolian Warm Acupuncture on iNOS/NO and Inflammatory Cytokines in the Hippocampus of Chronic Fatigue Rats.

The inducible nitric oxide synthase/nitric oxide (iNOS/NO) signaling pathway and inflammatory cytokines play important roles in the pathogenesis of exercise-induced fatigue. Studies have found that Mongolian warm acupuncture (WA) could alleviate exercise-induced fatigue. However, the exact mechanisms underlying its effects remain unclear. In the present study, we investigated the effects of Mongolian WA on iNOS/NO signaling pathway and proinflammatory cytokines in a chronic exhaustive swimming-induced fatigue rat model. Animals were randomly divided into Control group, Ctrl + WA group, Model group, and Model + WA group. The body weight, exhaustive swimming time test, and Morris water maze test were performed before and after the chronic exhaustive swimming. The serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and iNOS were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-1ß, IL-6, TNF-α, IFN-γ, and iNOS in the hippocampus were measured by real-time polymerase chain reaction (RT-PCR). Moreover, the protein expression of iNOS in the hippocampus was measured by western blot, and the NO productions in the serum and hippocampus were detected by Griess reaction system. Chronic exhaustive exercise significantly reduced the body weight and exhaustive swimming time, and induced impairment in learning and memory, and which were reversed by WA treatment. Chronic exhaustive exercise also increased the expressions of iNOS and proinflammatory cytokines, while WA treatment significantly decreased the level of iNOS and proinflammatory cytokines. However, chronic exhaustive exercise did not affect the NO production. These findings demonstrated that WA could alleviate the chronic exhaustive swimming-induced fatigue and improve the learning and memory ability, and the actions might be related to the reduction of inflammatory response and iNOS expression.

Design and evaluation of biodegradable enteric microcapsules of amifostine for oral delivery.

Amifostine is the first FDA approved cytoprotective and chemoprotective agent in the treatment of cancer. However, it is not used widely because of its ineffectiveness when administered orally. The objective of this study was to prepare and evaluate the radioprotective efficacy of orally active amifostine enteric microcapsules (amifostine mc). The microcapsules were prepared by spray drying technique using Eudragit L100-55, and the yield was more than 80%. The particle size and surface morphology were determined by particle analyzer and scanning electron microscopy. Thermal characterization and infrared spectroscopy were evaluated as well. In vitro release assay found that more than 60% amifostine was released during the first 4h and the cumulative release ratio was up to approximately 90% in 24h at 37°C. The radioprotective efficacy was determined by 30-day survival study in mice acutely exposed to 6 Gy γ-ray irradiation. The results showed that all dose groups of amifostine microcapsules could significantly improve survival animal numbers and time. Furthermore, tissue distribution studies indicated the concentrations of the active metabolite WR-1065 in mice tissues of microcapsule group were higher than that of oral amifostine group at 180 min (p<0.01). These results demonstrated that oral administration of amifostine microcapsules provided effective radioprotection compared to the bulk drug.

[Effects of electric mildly-warmed needle of inner mongolian medicine on liver MDA and GSH content, GSH-Px and SOD activity in fatigue rats].

OBJECTIVE: To investigate the effect of electric mildly-warmed needle of inner Mongolian medicine on changes of free radical metabolism in the liver tissue of rats with fatigue. METHODS: A total of 33 male SD rats were evenly randomized into control, model and electro-mildly-warmed needle (EMWN) groups. Fatigue model was established by forcing the rat to swim in a water pool till exhaustion, once daily, continuously for 21 days. "Dinghui" (central spot of the bregmatic bone) and "Xinxue" (the center of the depression beneath the 7th thoracic vertebra) were punctured with silver needle which was warmed electrically by using a MLY-I Electrical Needle-warming Apparatus, once every 3 days. 7 sessions altogether. After decapitation, the rat's liver was taken, homogenated and centrifuged for detecting malondialdehyde (MDA) content with thio-barbituric acid, reduced glutathione (GSH) contents, glutathione peroxidase (GSH-Px) activity with chromatometry and superoxide dismutase (SOD) activity with xanthine oxidase method respectively. RESULTS: Compared with control group, liver GSH content, GSH-Px and SOD activity in model group lowered significantly (P < 0.05, 0.01), while in comparison with model group, these 3 indexes of EMWN group increased considerably (P < 0.05, 0.01). No significant differences were found among 3 groups in MDA levels (P > 0.05). The results showed that the effect of mildly-warmed needle treatment could resist fatigue induced decline of activity of antioxidant enzymes. CONCLUSION: Electric mildly-warmed needle therapy of inner Mongolian medicine can raise the activity of antioxidant enzymes in liver tissue of fatigue rats, which may underlie the action of mildly-warmed needle in improving fatigue.