Advance in Traditional Chinese Medicine for Alzheimer's disease by regulating microglia / 中国药理学通报

Microglia, the main immune macrophages in the central nervous system, can be highly involved in the occurrence and development of Alzheimer's disease(AD)through microglia polarization and receptor protein expression. Traditional Chinese Medicine has been demonstrated to have regulatory effects on MG. Many active components in Traditional Chinese herbs play important roles in decreasing β-amyloid peptide(Aβ)accumulation, inhibiting neuro-inflammation and regulating microglia polarization etc. In this study the role of microglia in the pathogenesis of AD and the mechanism by which Traditional Chinese Medicine regulating microglia are reviewed to provide a reference for the treatment of AD.

Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model / 中国中药杂志

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Effects of components in stasis-resolving and collateral-dredging Chinese herbal medicines on angiogenesis and inflammatory response of human umbilical vein endothelial cells induced by VEGF / 中国中药杂志

The present study investigated the mechanism of components in stasis-resolving and collateral-dredging Chinese herbal medicines, including scutellarin(Scu), paeonol(Pae), and hydroxy safflower yellow A(HSYA), in the treatment of psoriasis by regulating angiogenesis and inflammation. The human umbilical vein endothelial cells(HUVECs) cultured in vitro were divided into a normal group, a model group, a VEGFR tyrosine kinase inhibitor Ⅱ(VRI) group, and Scu, Pae, and HSYA groups with low, me-dium, and high doses. Cell viability was detected by the CCK-8 assay. Cell migration was detected by wound healing assay. Tube formation assay was used to measure the tube formation ability. Western blot was used to detect the protein expression of the VEGFR2/Akt/ERK1/2 signaling pathway. The secretion levels of inflammatory cytokines IFN-γ, IL-1β, IL-6, and TNF-α were detected by ELISA. The results showed that compared with the model group, all the Scu, Pae, and HSYA groups could reduce cell viability, inhibit cell migration and tube formation(P<0.05, P<0.01), and down-regulated the protein expression of VEGFR2, p-VEGFR2, Akt, p-Akt, ERK1/2, and p-ERK1/2. Scu and Pae could down-regulate VEGFR2 expression(P<0.05, P<0.01), while other groups only showed a downward trend. Scu and Pae significantly reduced IFN-γ and IL-6 levels(P<0.01), and HSYA significantly reduced the levels of IFN-γ, IL-1β, and IL-6(P<0.01). Scu, Pae, and HSYA had no significant effect on TNF-α. The results suggested that Scu, Pae, and HSYA may exert a therapeutic role in psoriasis-related angiogenesis and inflammation by inhibiting VEGFR2/Akt/ERK1/2 signaling pathway and inhibiting the secretion of IFN-γ, IL-1β, and IL-6.

Correlation of Platelet and Coagulation Function with Blood Stasis Syndrome in Coronary Heart Disease: A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD).@*METHODS@#The protocol for this meta-analysis was registered on PROSPERO (CRD42019129452). PubMed, Excerpta Medica Database (Embase), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to 1st June, 2020. Trials were considered eligible if they enrolled BSS and non-BSS (NBSS) patients with CHD and provided information on platelet and coagulation function. The platelet function, coagulation function, and fibrinolytic activity were compared between the BSS and NBSS groups. Forest plots were generated to show the SMDs or ESs with corresponding 95% CIs for each study. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity.@*RESULTS@#The systematic search identified 1,583 articles. Thirty trials involving 10,323 patients were included in the meta-analysis. The results showed that mean platelet volume, platelet distribution width, platelet aggregation rate, platelet P selectin, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1 α), and TXB2/6-keto-PGF1 α were higher in the BSS group than in the NBSS group (P<0.05 or P<0.01). Activated partial thromboplastin time was lower in the BSS group than in the NBSS group in the acute phase of CHD (P<0.01). The R and K values in thromboelastography and tissue plasminogen activator (t-PA) and t-PA/PAI-1 were lower in the BSS group than in the NBSS group (all P<0.01). No difference was found in the results of platelet count, plateletcrit, maximum amplitude, von Willebrand factor, prothrombin time, thrombin time, international normalized ratio, etc. between groups.@*CONCLUSIONS@#Increased platelet function, hypercoagulability, and decreased fibrinolytic activity were found among CHD patients with BSS.

Research progress of intervention of Chinese herbal medicine and its active components on human coronavirus / 中国中药杂志

The outbreak caused by 2019 novel coronavirus(2019-nCoV) is still spreading, posing a great threat to the safety and health of general population. However, there have not been any effective drugs for treatment, with symptomatic treatment and prevention prevailing. The treatment plans of severe acute respiratory syndrome(SARS) and Middle East respiratory syndrome(MERS) are often used for reference in clinic. The advantages of traditional Chinese medicine(TCM) in treating SARS and MERS are that it can intervene and block the progression of disease in early stage, significantly reduce symptoms, shorten the treatment duration of patients, reduce complications and side effects caused by hormone therapy. The coronavirus disease 2019(COVID-19) belongs to the category of TCM epidemic diseases. Chinese patent medicines and prescriptions in medical observation and clinical treatment were recommended in the "pneumonia diagnosis and treatment plan for new coronavirus infection"(trial version fifth) of the National Health Commission of the People's Republic of China. Qingfei Paidu Decotion was recommended for the treatment of COVID-19 by the National Health Commission of the People's Republic of China and National Administration of Traditional Chinese Medicine. TCM shows good clinical efficacy and great potential in the treatment of COVID-19. Previous studies of TCM have shown broad-spectrum antiviral activity, providing a variety of sources for the discovery of new antiviral drugs. In this paper, we reviewed traditional Chinese medicines and its active ingredients in the hope of bringing novel inspirations to the drug screening and clinical treatment for COVID-19.

Effect of extraction of saffron crocus on mitochondrial dynamics in ischemia/reperfusion rats / 中国药理学通报

Aim To investigate the protection mecha-nism of the extraction of the saffron crocus in ischemia/reperfusion rats. Methods Hematoxylin-eosin stai-ning, electron microscopy, and neurological assess-ments were performed in a transient middle cerebral ar-tery occlusion ( tMCAO ) rat model. The role of dy-namin-related protein 1 ( Drp1 ) and optic atrophy 1 ( Opa1 ) , the two key regulators of mitochondrial fis-sion and fusion in ischemic brain damage in vivo were observed. Results In ischemia/reperfusion rats, the extraction of the saffron crocus increased the level of protein Opa1 and decreased the level of protein Drp1 . Conclusions Inhibition of Drp1 and promotion of Opa1 , which means to maintain balancing mitochondri-al dynamics, is proposed as an efficient strategy for neuroprotection against ischemic brain damage.

Experimental study on the mechanism of evaporative dry eye treated by Qingxuan decoction in rabbits / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To study the mechanism and effect of Qingxuan decoction on evaporative dry eye in rabbit model. ·METHODS: Totally 25 healthy male Japanese white rabbits were randomly divided into 5 groups: control group, model group, western medicine group, high dose of Qingxuan decoction group, low dose of Qingxuan decoction group. The blank control group did not do any treatment. The improved dry eye model of rabbit was prepared by the improved method of glandular burning of the eyelid plate. The high and low dose group were given daily 27. 2mg/kg, 6. 8mg/kg Qingxuan decoction by gavage. The model group was intragastric with the same amount of normal saline every day. The western medicine group with tobramycin and dexamethasone ophthalmic ointment 1 drops, once a day. The treatment were administered continuously for 28d. At 14d before the experiment, 7d before the experiment, 7d after the model, and 14d after the model, all the rabbits were tested by Schirmer Ⅰ test ( SⅠt) and break-up time (BUT). On the 15d after modeling, the animals were sacrificed by excessive anaesthesia. Rabbit ocular surface tissue sections were prepared. Hematoxylin - eosin staining method was used to observe the corneal morphological changes in each group. The concentrations of TNF-α, IL-1 and IL-6 in the ocular surface of rabbits were detected by ELISA. ·RESULTS: (1) BUT, SⅠt: 7d after the model had been prepared, BUT and SⅠt of the model group and the western medicine group, high dose and low dose of Qingxuan decoction group was improved ( P< 0. 05 );Those of western medicine group, high dose and low dose of Qingxuan Decoction group compared with the model group, were significantly different (P<0. 05). (2) TNF-α, IL-1, IL-6: The ELISA assay showed that TNF-α and IL-1, IL-6 concentration in the model group rabbits was significantly higher than those of the control group, TNF-α and IL-1, IL-6 concentration in western medicine group and high dose group of rabbits was significantly lower than those in the model group, the differences were statistically significant (P<0. 05), and in high dose group the effect was better than that of Western medicine group. ( 3 ) Histopathological examination: on the 14d after the model, the corneal epithelium in the blank control group was stratified well. The cells in the base were columnar, near the surface, the cornea epithelium showed a squamous change. Conjunctiva showed complete epithelial layer and subconjunctival tissue layer, and goblet cells arranged closely. The number of corneal epithelial cells in model group was reduced or even stripped, and the matrix layer was disorder; Irregular loss of conjunctival epithelial cell layer and a large decrease in goblet cells. The corneal morphology of the rabbits in the western medicine group and the high dose group was close to the normal group, and the number of conjunctival goblet cells was not significantly different from that in the blank control group. ·CONCLUSION: The expression of Qingxuan decoction can inhibit the inflammatory reaction through down -regulation of TNF-α and IL-1, IL-6 and in evaporative dry eye rabbit cornea and conjunctiva, so as to improve the ocular symptoms, increase tear secretion, prolong the time of BUT.

Paeoniflorin Promotes Angiogenesis in A Vascular Insufficiency Model of Zebrafish in vivo and in Human Umbilical Vein Endothelial Cells in vitro / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the pro-angiogenic effects of paeoniflorin (PF) in a vascular insufficiency model of zebrafish and in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>In vivo, the pro-angiogenic effects of PF were tested in a vascular insufficiency model in the Tg(fli-1:EGFP)y1 transgenic zebrafish. The 24 h post fertilization (hpf) embryos were pretreated with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor II (VRI) for 3 h to establish the vascular insufficiency model and then post-treated with PF for 24 h. The formation of intersegmental vessels (ISVs) was observed with a fluorescence microscope. The mRNA expression of fms-like tyrosine kinase-1 (flt-1), kinase insert domain receptor (kdr), kinase insert domain receptor like (kdrl) and von Willebrand factor (vWF) were analyzed by real-time polymerase chain reaction (PCR). In vitro, the pro-angiogenic effects of PF were observed in HUVECs in which cell proliferation, migration and tube formation were assessed.</p><p><b>RESULTS</b>PF (6.25-100 μmol/L) could rescue VRI-induced blood vessel loss in zebrafish and PF (25-100 μmol/L), thereby restoring the mRNA expressions of flt-1, kdr, kdrl and vWF, which were down-regulated by VRI treatment. In addition, PF (0.001-0.03 μmol/L) could promote the proliferation of HUVECs while PF stimulated HUVECs migration at 1.0-10 μmol/L and tube formation at 0.3 μmol/L.</p><p><b>CONCLUSION</b>PF could promote angiogenesis in a vascular insufficiency model of zebrafish in vivo and in HUVECs in vitro.</p>

Effect of Ginkgo biloba extract (EGb50) on mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation injury / 中国中药杂志

Ischemic cerebrovascular disease and cerebral ischemia/reperfusion injury threaten the health of human being. We studied the protective effect of Ginkgo biloba extract 50 (EGb50) on the mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation (H/R) injury and explored its mechanisms, so as to provide new ideas for studies on the treatment for ischemic cerebrovascular disease. We established the H/R injury model in SH-SY5Y cells after administrating EGb50. Subsequently, the mitochondrial membrane potential and the concentration of intracellular Ca²⁺ were measured by flow cytometer. The levels of optic atrophy1 (Opa1) and dynamin-like protein 1 (Drp1) were evaluated by immunofluorescence and western blot. The results showed that the mitochondrial membrane potential was decreased and the level of intracellular Ca²⁺ was increased after H/R injury. Moreover, the expression of mitochondrial fusion protein Opa1 was decreased, while the expression of mitochondrial fission protein Drp1 was increased. However, EGb50 significantly increased the mitochondrial membrane potential and suppressed the level of intracellular Ca²⁺. In addition, EGb50 increased the expression of Opa1 and decreased the expression of Drp1. The results demonstrated that EGb50 has a neuroprotective effect on SH-SY5Y cells after H/R injury, and could improve the energy metabolism and mitochondrial function. The underlying mechanisms may be associated with the regulation of mitochondrial fusion and fission, which provided data support for the treatment of ischemic cerebrovascular disease with EGb50.

Treatment of cardiovascular disease with Xiongshao capsule / 中国中药杂志

Cardiovascular diseases have the characteristics of high morbidity and high mortality, and are recognized as the first cause of death by World Health Organization in World Health Statistics 2016. In recent years, traditional Chinese medicines have been widely applied in the treatment of cardiovascular diseases, while studies for integrated traditional Chinese and western medicines for treating cardiovascular diseases have made a great progress. Xiongshao capsule was developed by Academician Chen Keji according to classic formula Xuefu Zhuyu decoction and composed of effective parts of Rhizoma Ligusticum Wallichii and Radix Paeonia Rubra, with remarkable therapeutic effects on angina pectoris, restenosis after percutaneous coronary intervention(PCI), atherosclerosis, dyslipidemia and so on. In this review, basic and clinical studies for the effect of Xiongshao capsule in treating cardiovascular diseases were reviewed to provide reference for reasonable clinical use and example for new traditional Chinese medicine development and application under the guidance of theory of integrated traditional Chinese and western medicines.

Synergistic effects of Chuanxiong-Chishao herb-pair on promoting angiogenesis at network pharmacological and pharmacodynamic levels / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the synergistic effects of Chuanxiong-Chishao herb-pair (CCHP) on promoting angiogenesis in silico and in vivo.</p><p><b>METHODS</b>The mechanisms of action of an herb-pair, Chuanxiong-Chishao, were investigated using the network pharmacological and pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation. A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao. Furthermore, the therapeutic effects and putative molecular mechanisms of Chuanxiong-Chishao actions were experimentally validated in a chemical-induced vascular insuffificiency model of transgenic zebrafifish in vivo. The mRNA expression of the predicted targets were further analyzed by real-time polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The computational prediction results found that the compounds in Chuanxiong have antithrombotic, antihypertensive, antiarrhythmic, and antiatherosclerotic activities, which were closely related to protecting against hypoxic-ischemic encephalopathy, ischemic stroke, myocardial infarction and heart failure. In addition, compounds in Chishao were found to participate in anti-inflflammatory effect and analgesics. Particularly, estrogen receptor α (ESRα) and hypoxia-inducible factor 1-α (HIF-1α) were the most important potential protein targets in the predicted results. In vivo experimental validation showed that post-treatment of tetramethylpyrazine hydrochloride (TMP•HCl) and paeoniflorin (PF) promoted the regeneration of new blood vessels in zebrafifish involving up-regulating ESRα mRNA expression. Co-treatment of TMP•HCl and PF could enhance the vessel sprouting in chemical-induced vascular insuffificiency zebrafifish at the optimal compatibility proportion of PF 10 μmol/L with TMP•HCl 1 μmol/L.</p><p><b>CONCLUSIONS</b>The network pharmacological strategies combining drug target prediction and network analysis identified some putative targets of CCHP. Moreover, the transgenic zebrafifish experiments demonstrated that the Chuanxiong-Chishao combination synergistically promoted angiogenic activity, probably involving ESRα signaling pathway.</p>

Efficacy and Bleeding Risks of Ticagrelor Replacement for Treating Elderly Acute Coronary Syndrome Patients With Low Response to Clopidogrel / 中国循环杂志

Objective: To observe the efficacy of ticagrelor for treating elderly acute coronary syndrome (ACS) patients with elective PCI and having low response to clopidogrel; to explore the bleeding risks induced by ticagrelor replacement. Methods: A total of 945 ACS patients ≥ 65 years treated in our hospital from 2014-01 to 2017-01 were enrolled. All patients received aspirin and clopidogrel dual antiplatelet therapy (DAPT), thrombelastography (TEG) was used to detect platelet inhibition rate when DAPT ≥ 5 days. Based on platelet inhibition rate, the patients were divided into 2 groups:Ticagrelor replacement group, n=293 patients with low response to clopidogrel and switched to ticagrelor treatment, when adjusted DAPT ≥ 5 days, platelet inhibition rate was rechecked to compare the changes; Clopidogrel group, the patients were continuously treated by the same medication, n=652. The patients were followed-up for 3 months, bleeding events were evaluated by TIMI criteria and compared between 2 groups. Risk factors of ticagrelor induced bleeding were assessed by multivariate Logistic regression analysis. Results: Platelet inhibition rates in Ticagrelor replacement group were (51.70±42.90) %, (48.99±41.85) % and (55.08±25.70) % at (5-7) d, (8-14) d and (15-90) d ticagrelor treatment, which were higher than previous clopidogrel treatment (14.50±24.15) %, all P<0.05. The incidences of severe bleeding events were similar between 2 groups, P=0.96. Multivariate Logistic regression analysis presented that female (OR=4.329, P=0.000), low body weight (OR=0.817, P=0.039) and elevated fasting blood glucose (OR=1.251, P=0.028) were the independent risk factors for bleeding complication in ticagrelor treated elderly ACS patients. Conclusion: Compared with clopidogrel, ticagrelor may faster and more effectively inhibit platelet aggregation without increasing severe bleeding; female, low body weight and elevated fasting blood glucose were the independent risk factors for bleeding complication in ticagrelor treated elderly ACS patients with elective PCI.

Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl-induced liver injury / 中国天然药物

Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.

Pro-angiogenic activity of notoginsenoside R1 in human umbilical vein endothelial cells in vitro and in a chemical-induced blood vessel loss model of zebrafish in vivo / 中国结合医学杂志

<p><b>OBJECTIVE</b>This study aimed at investigating whether notoginsenoside R1 (R1), a unique saponin found in Panax notoginseng could promote angiogenic activity on human umbilical vein endothelial cells (HUVECs) and elucidate their potential molecular mechanisms. In addition, vascular restorative activities of R1 was assessed in a chemically-induced blood vessel loss model in zebrafish.</p><p><b>METHODS</b>The in vitro angiogenic effect of R1 was compared with other previously reported angiogenic saponins Rg1 and Re. The HUVECs proliferation in the presence of R1 was determined by cell proliferation kit II (XTT) assay. R1, Rg1 and Re-induced HUVECs invasion across polycarbonate membrane was stained with Hoechst-33342 and quantified microscopically. Tube formation assay using matrigelcoated wells was performed to evaluate the pro-angiogenic actions of R1. In order to understand the mechanism underlying the pro-angiogenic effect, various pathway inhibitors such as SU5416, wortmannin (wort) or L-Nω-nitro- L-arginine methyl ester hydrochloride (L-NAME), SH-6 were used to probe the possible involvement of signaling pathway in the R1 mediated HUVECs proliferation. In in vivo assays, zebrafish embryos at 21 hpf were pre-treated with vascular endothelial growth factor (VEGF) receptor kinase inhibitor II (VRI) for 3 h only and subsequently post-treated with R1 for 48 h, respectively. The intersegmental vessels (ISVs) in zebrafish were assessed for the restorative effect of R1 on defective blood vessels.</p><p><b>RESULTS</b>R1 could stimulate the proliferation of HUVECs. In the chemoinvasion assay, R1 significantly increased the number of cross-membrane HUVECs. In addition, R1 markedly enhanced the tube formation ability of HUVECs. The proliferative effects of these saponins on HUVECs were effectively blocked by the addition of SU5416 (a VEGF-KDR/Flk-1 inhibitor). Similarly, pre-treatment with wort [a phosphatidylinositol 3-kinase (PI3K)-kinase inhibitor], L-NAME [an endothelial nitric oxide synthase (eNOS) inhibitor] or SH-6 (an Akt pathway inhibitor) significantly abrogated the R1 induced proliferation of HUVECs. In chemicallyinduced blood vessel loss model in zebrafish, R1 significantly rescue the damaged ISVs.</p><p><b>CONCLUSION</b>R1, similar to Rg1 and Re, had been showed pro-angiogenic action, possibly via the activation of the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways. Our findings also shed light on intriguing pro-angiogenic effect of R1 under deficient angiogenesis condition in a pharmacologic-induced blood vessels loss model in zebrafish. The present study in vivo and in vitro provided scientific evidence to explain the ethnomedical use of Panax notoginseng in the treatment of cardiovascular diseases, traumatic injuries and wound healing.</p>

L-tetrahydropalamatine inhibits tumor necrosis factor-α-induced monocyte-endothelial cell adhesion through downregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 involving suppression of nuclear factor-κ B signaling pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether I-tetrahydropalmatine (I-THP), an alkaloid mainly present in Corydalis family, could ameliorate early vascular inflammatory responses in atherosclerotic processes.</p><p><b>METHODS</b>Fluorescently labeled monocytes were co-incubated with human umbilical vein endothelial cells (HUVECs), which were pretreated with I-THP and then simulated with tumor necrosis factor (TNF)-α in absence of I-THP to determine if I-THP could reduce thecytokine-induced adhesion of monocytes to HUVECs. Then I-THP were further studied the underlying mechanisms through observing the transcriptional and translational level of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the nuclear translocation of nuclear factor (NF)-κ B in HUVECs.</p><p><b>RESULTS</b>L-THP could block TNF-α-induced adhesion of monocytes to HUVECs and could significantly inhibited the expression of ICAM-1 and VCAM-1 on cell surface by 31% and 36% at 30 μ mol/L. L-THP pretreatment could also markedly reduce transcriptional and translational level of VCAM-1 as well as mildly reduce the total protein and mRNA expression levels of ICAM-1. Furthermore, I-THP attenuated TNF-α-stimulated NF-κ B nuclear translocation.</p><p><b>CONCLUSION</b>These results provide evidences supporting that I-THP could be a promising compound in the prevention and treatment of the early vascular inflammatory reaction in atherosclerosis by inhibiting monocyte adhesion to vascular endothelial cell through downregulating ICAM-1 and VCAM-1 in vascular endothelial cell based on suppressing NF-κ B.</p>

Effect of Sailuotong capsule on mitochondrial dynamics in focal cerebral ischemia/reperfusion rats / 中国中药杂志

To observe the protective effect and mechanism of Sailuotong capsule in focal cerebral ischemia/reperfusion. The 90 min middle cerebral artery occlusion (MCAO) reperfusion model was established. The expressions of dynamin-related protein 1 ( Drp1) and optic atrophy 1 (Opa1) were tested by Western blot. The transmission electron microscope was used to observe the changes in the mitochondrial ultra-structure. The pathological morphological changes were observed through the HE staining. The immunohistochemical method was used to test Drp1 and Opa1 expressions. Sailuotong capsule (33, 16.5 mg x kg(-1), ig) can inhibit the abnormal mitochondrial fission and fusion in the cortical area on the ischemia side and the mitochondrial fission gene expression and promote the mitochondrial fusion gene Opa1 expression, so as to alleviate the energy metabolism disorder caused by ischemia/reperfusion. Sailuotong capsule can inhibit the abnormal mitochondrial dynamics in peri-ischemic regions and maintain the normal morphology of mitochondria, which may be the mechanism of Sailuotong capsule in promoting the self-recovery function in the ischemic brain region.

Effects of chest compressions on cardiorespiratory function in a non-arrested porcine model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effects of chest compressions to hemodynamic and respiratory parameters during hands-only cardiopulmonary resuscitation (CPR) in a non-arrested patient who suddenly collapses are confusing. In this research, we investigated the effects of chest compressions in a non-arrested porcine model.</p><p><b>METHODS</b>Fourteen male domestic pigs were randomized into sham control group (SHAM group, only anesthetized and instrumented without chest compression, n = 6) or chest compression group (CC group, 2 minutes of chest compressions, n = 8). Continuous hemodynamic parameters, dynamic lung compliance (Cdyn), and blood gas analysis outcomes were recorded. Serum levels of catecholamine were measured at baseline and 2 minutes, 30 minutes, 4 hours, and 24 hours after chest compressions. Chest computed tomography (CT) was performed at 30 minutes and 24 hours. Conventional histopathology evaluation was performed.</p><p><b>RESULTS</b>After two minutes of chest compressions in the CC group, heart rate and extravascular lung water increased significantly; mean arterial pressure, stroke volume, and global ejection fraction significantly decreased. Cdyn significantly decreased to valley levels at 30 minutes and slowly recovered. Compared with the baseline, serum levels of catecholamine significantly increased at 2 minutes and rapidly decreased 24 hours later. At 30 minutes after chest compressions, chest CT showed local exudation, which was absorbed 24 hours later.</p><p><b>CONCLUSIONS</b>This research showed that 2 minutes of chest compressions causes various heart and lung tissue damage in the normal a normal porcine model. It also impacts the hemodynamic and Cdyn.</p>

Synergism between carnosic acid and arsenic trioxide on induction of acute myeloid leukemia cell apoptosis is associated with modulation of PTEN/Akt signaling pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the synergistic effects of carnosic acid (CA) with arsenic trioxide (As₂O₃) on proliferation and apoptosis in HL-60 human myeloid leukemia cells, and the major cellular signaling pathway involved in these effects.</p><p><b>METHODS</b>HL-60 cellular proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Cell cycle distribution and apoptosis were monitored by flow cytometry. The activation of casepase-9, Bcl-2-associated agonist of cell death (BAD), p-BAD, p27, phosphatase and tensin homolog deleted on chromosome ten (PTEN), Akt, p-Akt was assessed by Western blot analysis. The expression of PTEN mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR) analysis.</p><p><b>RESULTS</b>CA reduced HL-60 cell viability in a dose- and time-dependent manner, and induced G1 arrest and apoptosis. Moreover, CA upregulated PTEN expression, blocked the Akt signaling pathway, subsequently inhibited phosphorylation of BAD, reactivated caspase-9, and elevated levels of p27. CA also augmented these effects of As₂O₃.</p><p><b>CONCLUSION</b>CA might be a novel candidate of the combination therapy for leukemia treatment; these effects were apparently associated with the modulation of PTEN/Akt signaling pathway.</p>

Research, design and application of model NSE-1 neck muscle training machine for pilots / 生物医学工程学杂志

Pain in the cervical region of air force pilots, who are exposed to high G-forces, is a specifically occupational health problem. To minimize neck problems, the cervical muscles need specific strength exercise. It is important that the training for the neck must be carried out with optimal resistance in exercises. The model NSE-1 neck training machine for pilots was designed for neck strengthening exercises under safe and effective conditions. In order to realize the functions of changeable velocity and resistant (CVR) training and neck isometric contractive exercises, the techniques of adaptive hydraulics, sensor, optic and auditory biological feedback, and signal processing were applied to this machine. The training system mainly consists of mechanical parts (including the chair of flexion and extension, the chair of right and left lateral flexion, the components of hydraulics and torque transformer, etc.), and the software of signal processing and biological feedback. Eleven volunteers were selected for the experiments of neck isometric contractive exercises, three times a week for 6 weeks, where CVR training (flexion, extension, right, left lateral flexion) one time a week. The increase in relative strength of the neck (flexion, extension, left and right lateral flexion) was 70.8%, 83.7%, 78.6% and 75.2%, respectively after training. Results show that the strength of the neck can be increased safely, effectively and rapidly with NSE-1 neck training machine to perform neck training.

Study on neck injuries in military pilots / 医用生物力学

Objective To investigate the present situation of neck injuries in military pilots, analyze possible factors that induce neck injuries and how such injuries could influence flight training, and provide suggestions for relevant physiological researches and engineering solutions. Method Questionnaires were carried out among 1 924 military pilots, including pilots of primary trainer, attacker, fighter, bomber, transporter and helicopter. The questionnaire consist of 2 parts: (1) pilots’ basic information, such as unit, age, type of aircraft, flying hours, height, weight, etc. (2) relevant issues on neck injuries, including symptoms and their influences on flight, reasons that cause the injuries, etc. Statistical analyses were conducted according to the questionnaire results. Results The investigation showed that 71.3% of the pilots had uncomfortable neck symptoms and 60.4% of them had befallen such symptoms during flight. 33.7% of the pilots had suffered neck pain and 19.2% of them reported that such pains took place during flight. Factors such as acceleration, weight of helmet and long duration of flight would be the main reasons resulting in the discomfort of neck. Bomber pilots showed the highest proportion either on the neck discomfort or on the neck pain. Conclusions Neck injuries have become the frequently occurring illness in Chinese military pilots and have affected their daily flight. The study also foresees an increased tendency on pilots’ neck injuries due to the growing requirements of flight load and training strength on fighter and attacker pilots. Therefore, great importance should be attached on neck injuries of military pilots and further studies should be conducted on physiological investigations and engineering solutions.