Shashen-Maidong Decoction inhibited cancer growth under intermittent hypoxia conditions by suppressing oxidative stress and inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lung cancer is one of the most common malignant tumours and has become the leading cause of cancer-related deaths worldwide. Abnormal microcirculation during tumour growth leads to intermittent hypoxia (IH), which is responsible for promoting cancer cell proliferation and migration. Patients with advanced lung cancers show deficiency of both Qi and Yin Syndrome (DQYS) in TCM, and studies have confirmed that IH exposure is related to DQYS. Shashen-Maidong Decoction (SMD), has been widely applied clinically targeting DQYS and has a long history for treating lung cancer by nourishing the body's "zheng qi" and resisting "xie qi". However, whether SMD could be beneficial to lung cancer under IH conditions remains unclear. AIM OF THE STUDY: This study aimed to clarify the effects and mechanism of SMD on non-small cell lung cancer (NSCLC) growth under IH conditions. MATERIALS AND METHODS: C57 mice were injected subcutaneously into the right axilla with Lewis lung cancer (LLC) cells and exposed to IH conditions (21%-5% O2, 5 min/cycle, 8 h/day) for 21 days. SMDs were orally treated with different concentrations (2.6, 5.2 or 10.4 g/kg/day) 30 min before IH exposure. Tumour proliferation and migration were assessed by HE and IHC staining, and oxidative stress was assessed by DHE staining and MDA or SOD detection. IL-6, IL-1ß and TNF-α levels were assessed by IHC staining, and the IL-6/JAK2/STAT3 signalling pathway was detected by western blotting. RESULTS: Our results showed that SMD treatment inhibited tumour growth and liver metastasis in LLC-bearing mice exposed to IH, decreased Ki67, CD31, VEGF, and MMP-2, and increased E-cadherin expression in tumourt tissue. SMD reduced ROS production, increased SOD levels and SOD-2 expression, and decreased MDA levels and NOX-2 expression. SMD decreased IL-6, IL-1ß and TNF-α levels, reduced IL-6 expression and inhibited JAK2 and STAT3 phosphorylation. Additionally, SMD treatment improved DQYS and liver and kidney function in LLC-bearing mice under IH conditions. CONCLUSION: Our research suggests that SMD treatment can inhibit tumour growth in mice exposed to IH. The antitumour effect of SMD may be related to attenuated oxidative stress and inflammation through inactivation of the IL-6/JAK2/STAT3 signalling pathway under IH conditions.

Shashen-Maidong Decoction improved chronic intermittent hypoxia-induced cognitive impairment through regulating glutamatergic signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which is associated with cognitive impairment. Previous study suggested CIH exposure could induce similar symptoms and signs to the clinical features of Deficiency of both Qi and Yin Syndrome (DQYS) in Traditional Chinese Medicine (TCM). Shashen-Maidong Decoction (SMD) has been applied clinically for DQYS for hundred years. However, SMD treatment could be beneficial to CIH induced cognitive impairment is still unclear. AIM OF THE STUDY: Therefore, the aim of this study was to investigate the effect of SMD treatment on CIH induced cognitive impairment, and to explore the related neuroprotective mechanism. MATERIALS AND METHODS: Mice were exposed to CIH for 5 weeks (8 h/day) and were orally treated with either vehicle or SMD (5.265 g/kg/day) 30 min before CIH exposure. Spatial memory was evaluated by Morris Water Maze and Y-Maze test. Synaptic morphology in hippocampus was observed by Golgi-Cox staining and Electron microscope, and NR2B-ERK signaling pathway were detected by western blotting. RESULTS: Our results showed that SMD treatment improved performance in either Morris Water Maze or Y-Maze test in mice exposed to CIH, increased spine density and postsynaptic density (PSD) thickness in hippocampus. SMD treatment suppressed the over-activation of NR2B/CaMKII/SynGAP induced by CIH exposure, enhanced ERK/CREB phosphorylation and increased PSD-95 and BDNF expression. CONCLUSION: SMD attenuates the CIH-induced cognitive impairment through regulating NR2B-ERK signaling pathway. Additionally, our findings provided that DQYS may be the potential therapeutic target for neurocognitive diseases in patients with OSA.

Influence of Tiaopi Huxin Decoction on Ventricular Remodeling and Prognosis of Chronic Heart Failure Based on Theory of Heart Spleen Correlation / 中国实验方剂学杂志

Objective:To observe clinical effect of Tiaopi Huxin decoction to chronic heart failure (CHF) and to study mechanism of action of anti-inflammatory and anti ventricular remodeling.Method:One hundred and forty patients were randomly divided into control group (70 cases) and observation group (70 cases) by random number table. And during the study, there were four patients for falling off and missing visit, two eliminated patients in control group, and 64 patients finished the study, and there were six patients for falling off and missing visit in observation group, so 64 patients finished the study. Two groups of patients got losartan potassium tablets, 50 mg/time, 1 time/day, metoprolol tablets, 200 mg/time, 1 time/day, spironolactone tablets, 20-40 mg/time, 1 time/day, control group Jingshe Yiqi granule 1 bag/time,3 times/day,flushed with boiling water, patients in observation group added Tiaopi Huxin decoction, 1 dose/day. The courses of treatment were 12 weeks. Before and after treatment, left ventricular ejection fraction (LVEF), left ventricular end diastolic dimension (LVEDd), leftventricular end-stolic diameter (LVEDs), stroke volume (SV), cardiac output (CO) and ratio of peak value of early diastolic velocity of mitral valve and peak velocity of late diastolic mitral valve (E/A) were recorded by echocardiography. And scores of Lee's heart failure, Qi deficiency and blood stasis, Minnesota Heart Failure Quality of life questionnaire (MLHFQ) and 6 minutes' walking test（6 MWT）were graded. And levels of N-terminal B-type natriuretic peptide (NT-proBNP), galactose lectin-3, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-17, transforming growth factor (TGF) - β and matrix metalloproteinase-9 (MMP-9) were detected.Result:After treatment, LVEDd and LVEDs were lower than that in control group (P<0.05). LVEF, SV, CO and E/A were higher than those in control group (P<0.05). And scores of Lee's heart failure, Qi deficiency blood stasis and MLHFQ were lower than those in control group (P<0.01). And 6 MWT was more than that in control group (P<0.01). And levels of NT-proBNP, galactose lectin 3, IL-17, IL-6, TNF-α, TGF-β and MMP-9 were lower than those in control group (P<0.01). Effect of cardiac function was better than that in control group (Z=2.191, P<0.05).Conclusion:On the basis of conventional western medicine treatment and according to theory of heart and spleen, Tiaopi Huxin decoction can improve the clinical symptoms and signs of heart failure, and it had effect of anti-inflammatory, and can improve ventricular remodeling, improve the exercise tolerance and quality of life of patients, improve the prognosis of heart failure, and its clinical effect is better than that of Western medicine alone.

Unique MicroRNAs Signature of Lymphocyte of Yang and Yin Syndromes in Acute Ischemic Stroke Patients.

OBJECTIVE: To identify the differentially expressed microRNAs (miRNAs) profiles of yang and yin syndromes in patients with acute ischemic stroke, and to provide the molecular basis of the classification of these two syndrome types in acute ischemic stroke patients. METHODS: A microarray assay was performed to assess the expression pattern of miRNAs in the lymphocyte of acute ischemic stroke patients. Target genes for the deregulated miRNAs were predicated using the online bioinformatic algorithms and functional annotation via Kyoto encyclopedia of genes and genomes pathway analysis for miRNAs predicted targets was carried out. Based on the predicted target genes of differentially expressed miRNAs, the miRNA-gene-network and miRNA-pathway-network were constructed. RESULTS: Yang score based on tongue texture, urine, dejecta, and appearance, etc. showed that clinical symptoms were distinct between yang and yin syndromes. There were significantly higher total leukocyte number and lower total protein level in patients with yang syndrome compared with those in patients with yin syndrome (P<0.05). Comprehensive miRNA analysis identified 36 unique down-regulated miRNAs in yang syndrome group, and 20 unique down-regulated and 2 unique up-regulated miRNAs in yin syndrome group. The key regulatory miRNAs, gene, and pathways in the yang syndrome were hsa-miR-93-5p and -320b, enabled homolog, the metabolic pathways and mitogen-activated protein kinase signaling pathways, respectively, while those in the yin syndrome were hsa-miR-424-5p and -106b-5p, CNOT4, hepatitis B and pathways in cancer, respectively. CONCLUSION: These results offered insight into the molecular basis underlying the different pathogenesis of yang or yin syndrome, providing clues for the individualized therapeutic strategies of acute ischemic stroke.

Discussions on ischemic stroke basic pathogenesis, blood stasis caused by deficiency of both Qi and Yin, and its therapeutic application of Yangyin Yiqi Huoxue / 中国中西医结合急救杂志

Based on our research team's clinical and basic research results of traditional Chinese medicine (TCM) in the prevention and treatment of ischemic stroke, and combined with TCM syndrome standard manifestations of this disease, wind, phlegm, fire, deficiency and blood stasis, this paper points out definitely that the basic pathogenesis of ischemic stroke is blood stasis caused by deficiency of both Qi and Yin. The pathogenic characteristics are deficiency in origin and excess in superficiality, and the wind, fire, phlegm, deficiency and blood stasis are related one another resulting in this disease; it is established that the basic syndrome types of this disease are deficiency of both Qi and Yin and static blood blocking the collaterals, and the therapeutic regime is a recipe including the TCM ingredients having the actions of nourishing yin, tonifying Qi and improving blood circulation (Yangyin Yiqi Huoxue) and according to the patient's individual variation of syndrome differentiation, the ingredients in the recipe can be added or subtracted. In this report, a new system of treatment for ischemic stroke based on syndrome differentiation is proposed.

Unique MicroRNAs Signature of Lymphocyte of Yang and Yin Syndromes in Acute Ischemic Stroke Patients / 中国结合医学杂志

OBJECTIVE@#To identify the differentially expressed microRNAs (miRNAs) profiles of yang and yin syndromes in patients with acute ischemic stroke, and to provide the molecular basis of the classification of these two syndrome types in acute ischemic stroke patients.@*METHODS@#A microarray assay was performed to assess the expression pattern of miRNAs in the lymphocyte of acute ischemic stroke patients. Target genes for the deregulated miRNAs were predicated using the online bioinformatic algorithms and functional annotation via Kyoto encyclopedia of genes and genomes pathway analysis for miRNAs predicted targets was carried out. Based on the predicted target genes of differentially expressed miRNAs, the miRNA-gene-network and miRNA-pathway-network were constructed.@*RESULTS@#Yang score based on tongue texture, urine, dejecta, and appearance, etc. showed that clinical symptoms were distinct between yang and yin syndromes. There were significantly higher total leukocyte number and lower total protein level in patients with yang syndrome compared with those in patients with yin syndrome (P<0.05). Comprehensive miRNA analysis identified 36 unique down-regulated miRNAs in yang syndrome group, and 20 unique down-regulated and 2 unique up-regulated miRNAs in yin syndrome group. The key regulatory miRNAs, gene, and pathways in the yang syndrome were hsa-miR-93-5p and -320b, enabled homolog, the metabolic pathways and mitogen-activated protein kinase signaling pathways, respectively, while those in the yin syndrome were hsa-miR-424-5p and -106b-5p, CNOT4, hepatitis B and pathways in cancer, respectively.@*CONCLUSION@#These results offered insight into the molecular basis underlying the different pathogenesis of yang or yin syndrome, providing clues for the individualized therapeutic strategies of acute ischemic stroke.

Analysis of Serum Transcriptome Characteristics of Patients with Yin and Yang Syndromes of Acute Ischemic Stroke / 中国实验方剂学杂志

Objective:To obtain the regulatory relationship between genes by screening the differentially expressed long non-coding ribonucleic acid(lncRNA), microRNA(miRNA) and messenger RNA(mRNA) in serum of patients with Yin and Yang syndromes of acute ischemic stroke, and to discuss the material basis and biological mechanism of formation of Yin and Yang syndromes of acute ischemic stroke from the transcriptome level. Method:The microarray chips were adopted to detect expression of lncRNA, mRNA and miRNA in serum of ischemic stroke patients with Yin and Yang syndromes and non-stroke subjects(10 cases each). Differential expression profiles related to Yin and Yang syndromes were selected by conjoint analysis. Further, the obtained differential genes were subjected to antisense lncRNA and mRNA co-expression analysis, gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) functional pathway analysis, and the intergenic regulatory relationship was obtained to predict the target genes of lncRNA. Partial differential genes in 40 patients(10 with Yang syndrome and 30 with Yin syndrome) were verified by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR). Result:The expression of 227 lncRNA, 54 mRNA and 4 miRNA were closely related to Yang syndrome, 394 lncRNA and 206 mRNA were closely related to Yin syndrome. Antisense lncRNA RP11-647P12.1 and RP11-677M14.2 may regulate the expression of neuron-derived neurotrophic factor(NDNF) and neurogranin(NRGN) by up-regulating the expression level in Yang syndrome. The differential expression of mRNA between Yin syndrome and Yang syndrome was mainly related to neurotransmitter receptor activity regulation, endocrine hormone regulation, inflammatory response, renin-angiotensin system and other pathways. Conclusion:There are differences in the expression profiles of lncRNA, miRNA and mRNA between Yin syndrome and Yang syndrome in acute ischemic stroke, which may be regulated by multiple pathways, such as blood pressure regulation, adrenergic receptor regulation, renin-angiotensin system and γ-aminobutyric acid(GABA). The transcriptome characteristics provide scientific basis for studying the biological basis of Yin syndrome and Yang syndrome in acute ischemic stroke.

<b>A Case Report of Hot Flush Successfully Treated with Formulations </b><b>for Yin-syndrome</b> / 日本東洋医学雑誌

We report a case of hot flush successfully treated with formulations for yin-syndrome. A 56-year-old female patient experienced hot sensations and sweating on her face post menopause. Her hot flush was improved slightly with kamishoyosan and ryokeijutsukanto, but her symptoms were aggravated whenever she became tired. The patient was reevaluated and her prescription was changed to hachimigan, based on symptoms related to yin-syndrome and hypofunction, and a lack of resistance at the lower abdomen with the abdominal palpation. The patient appeared to respond favorably. However, the patient was easily fatigued and her symptoms returned when she felt tired. Ninjinto was added to the prescription based on the patient's “stuck feeling in pit of the stomach”. Her hot flush resolved and she no longer became tired easily. Although the use of formulations for yang-syndrome are known to be useful for the treatment of hot flush, formulations for yin-syndrome may be effective for the treatment of hot flush depending on the state of the patient.

Effects of Xiaoke Wan on serum adiponectin levels in patients with type 2 diabetes mellitus / 国际中医中药杂志

Objective To investigate the effects of Xiaoke Wan on serum adiponectin levels in patients with type 2 diabetes metlitus. Methods A total of 60 2TDM patients with deficiency of both qi and yin syndrome were recruited into a control group and a treatment group randomly, 30 cases in each group. The treatment group was treated with Xiaoke Wan, and the control group was treated with glibenclamide. After 32 weeks, the changes of FPG, 2hPG, HbAIc, FINS, C-P, APN, HBCI,IRI and improvement of symptoms were compared between the two groups. Results Compared with glibenclamide, Xiaoke Wan can significantly improve the patients' symptoms, reduce the level of IRI (t=-1.590, P=-0.036), and increase serum APN (t=1.918, P=0.002). Conclusion Xiaoke Wan can significantly improve symptoms, reduce fasting blood glucose and 2 hour postprandial blood glucose, recover the secretion of adipouectin, decrease insulin resistance in 2TDM patients with deficiency of both qi and yin.