Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice / 中国中药杂志

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

Antioxidant effect of salvianolic acid B on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury / 中国结合医学杂志

<p><b>OBJETIVE</b>To investigate the neuroprotective effects and underlying mechanisms of salvianolic acid B (Sal B) extracted from Salvia miltiorrhiza on hippocampal CA1 neurons in mice with cerebral ischemia reperfusion injury.</p><p><b>METHODS</b>Forty male National Institute of Health (NIH) mice were randomly divided into 4 groups with 10 animals each, including the sham group, the model group, the SalB group (SalB 22.5 mg/kg) and the nimodipine (Nim) group (Nim 1 mg/kg). A mouse model of cerebral ischemia and reperfusion injury was established by bilateral carotid artery occlusion for 30 min followed by 24-h reperfusion. The malondialdehyde (MDA) content, the nitric oxide synthase (NOS) activity, the superoxide dismutase (SOD) activity and total antioxidant capability (T-AOC) of the pallium were determined by biochemistry methods. The morphologic changes and Bcl-2 and Bax protein expression in hippocampal CA1 neurons were observed by using hematoxylineosin staining and immunohistochemistry staining, respectively.</p><p><b>RESULTS</b>In the SalB group, the MDA content and the NOS activity of the pallium in cerebral ischemia-reperfusion mice significantly decreased and the SOD activity and the T-AOC significantly increased, as compared with the model group (P<0.05 or P<0.01). The SalB treatment also rescued neuronal loss (P<0.01) in the hippocampal CA1 region, strongly promoted Bcl-2 protein expression (P<0.01) and inhibited Bax protein expression (P<0.05).</p><p><b>CONCLUSIONS</b>SalB increases the level of antioxidant substances and decreases free radicals production. Moreover, it also improves Bcl-2 expression and reduces Bax expression. SalB may exert the neuroprotective effect through mitochondria-dependent pathway on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury and suggested that SalB represents a promising candidate for the prevention and treatment of ischemic cerebrovascular disease.</p>

Association between gene polymorphisms of Perforin 1 and hemophagocytic lymphohistiocytosis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate frequency distribution of gene polymorphisms of PRF1 gene in children with hemophagocytic lymphohistiocytosis (HLH), and to explore whether the possible gene polymorphisms of PRF1 gene confer an increased risk of susceptibility to HLH.</p><p><b>METHODS</b>Forty-eight children who were diagnosed with HLH between January 2009 and December 2013 (HLH group) and 100 healthy children (control group) were enrolled in this study. The gene polymorphisms in the coding region of PRF1 gene, which consists of three exons and two introns, were genotyped by PCR, followed by direct sequencing.</p><p><b>RESULTS</b>Three single nucleotide polymorphisms (SNPs) were revealed in the coding sequence of PRF1 in the 48 children with HLH. Seven SNPs were detected in the noncoding sequence. Other two SNPs in the noncoding sequence including rs10999426 and rs10999427 were detected only in 5 healthy children (5%). There was no significant difference in allelic frequencies of all the SNPs above between the HLH and control groups (P>0.05). Haplotype analysis showed there was a pair-wise linkage disequilibrium between rs10999426 and rs10999427 (D=1, r2=1), but there was no significant difference in the distribution of A-T haplotype between the HLH and control groups (P>0.05).</p><p><b>CONCLUSIONS</b>There is no association between gene polymorphisms of PRF1 gene and the susceptibility to HLH. There is a pair-wise linkage disequilibrium between rs10999426 and rs10999427, but a low detection rate of A-T haplotype in healthy children indicates that it might not play a protective role in the development of HLH.</p>

Effect of shRNA-mediated silencing of CTGF and TIMP-1 on mRNA expression of CTGF, TIMP-1, and PC I and secretion of extracellular matrix in rat hepatic stellate cells / 中华肝脏病杂志

To investigate the effect of short hairpin RNA (shRNA)-mediated silencing of CTGF and TIMP-1 in hepatic stellate cells (HSCs) on mRNA expression of TIMP-1, CTGF, and procollagen type-I (PC I), as well as secretion of extracellular matrix (ECM) proteins. Two recombinant expression plasmids harboring shRNAs against CTGF and TIMP-1 (psiRNA-GFP-CTGF and psiRNA-GFP-TIMP-1) were transfected alone or together into TGFb1-activated HSC-T6 cells. The mRNA expression levels of CTGF, TIMP-1, and PC I were detected by fluorescence quantitative PCR (FQ-PCR). The concentrations of secreted PC type-III, hyaluronate (HA), and laminin (LN) were measured by radioimmunoassay (RIA) of culture supernatants. FQ-PCR analysis showed that CTGFshRNA and TIMP-1shRNA specifically inhibited the expression of CTGF, TIMP-1, and PC I mRNA in activated HSC-T6 cells. The concentrations of secreted PC III, HA, and LN were decreased significantly in HSC-T6 cells with shRNA-silenced CTGF or TIMP-1 (P less than 0.01 or P less than 0.05). Moreover, HSC-T6 cells with shRNA-silenced CTGF and TIMP-1 showed a more robust decrease in synthesis of PC III, HA and LN (all, P less than 0.01), as well as in mRNA expression of PC I (P less than 0.05). CTGFshRNA and TIMP-1shRNA effectively inhibit expression of the respective target genes, as well as of PC I, and decrease secretion of ECM components from HSC-T6 cells. Silencing of both CTGF and TIMP-1 produces more robust effects than either in isolation. These data suggest that CTGF and TIMP-1 may be effective targets of shRNA-based gene therapy to treat liver fibrosis.

Neuroprotective effects of salvianolic acid B against oxygen-glucose deprivation/reperfusion damage in primary rat cortical neurons / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cerebral ischemia-reperfusion injury is the main reason for the loss of neurons in the ischemic cerebrovascular disease. Therefore, to deeply understand its pathogenesis and find a new target is the key issue to be solved. This research aimed to investigate the neuroprotective effects of salvianolic acid B (SalB) against oxygen-glucose deprivation/reperfusion (OGD/RP) damage in primary rat cortical neurons.</p><p><b>METHODS</b>The primary cultures of neonatal Wister rats were randomly divided into the control group, the OGD/RP group and the SalB-treatment group (10 mg/L). The cell model was established by depriving of oxygen and glucose for 3 hours and reperfusion for 3 hours and 24 hours, respectively. The neuron viability was determined by MTT assay. The level of cellular reactive oxygen species (ROS) was detected by fluorescent labeling method and spin trapping technique respectively. The activities of neuronal Mn-superoxide dismutase (Mn-SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) were assayed by chromatometry. The mitochondria membrane potential (ΔΨ(m)) was quantitatively analyzed by flow cytometry. The release rate of cytochrome c was detected by Western blotting. The neuronal ultrastructure was observed by transmission electron microscopy. Statistical significance was evaluated by analysis of variance (ANOVA) followed by Student-Newman-Keuls test.</p><p><b>RESULTS</b>OGD/RP increased the level of cellular ROS, but decreased the cell viability and the activities of Mn-SOD, CAT and GSH-PX; SalB treatment significantly reduced the level of ROS (P < 0.05); and enhanced the cell viability (P < 0.05) and the activities of these antioxidases (P < 0.05). Additionally, OGD/RP induced the fluorescence value of ΔΨ(m) to diminish and the release rate of cytochrome c to rise notably; SalB markedly elevated the level of ΔΨ(m) (P < 0.01) and depressed the release rate of cytochrome c (P < 0.05); it also ameliorated the neuronal morphological injury.</p><p><b>CONCLUSION</b>The neuroprotection of SalB may be attributed to the elimination of ROS and the inhibition of apoptosis.</p>

Effects of salvianolic acid B on cerebral energy charge and activity of ATPase in mice with cerebral ischemia / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of salvianolic acid B (SalB) on high energy phosphate and activity of ATPase of cerebral ischemia in mice, and to study the role of SalB on hydrocephalus further.</p><p><b>METHOD</b>NIH mice were divided into four groups randomly: Sham-operated group, cerebral ischemia group, SalB-treated group and Nimodipine (Nim)-collated group. In Sal B-treated group, mice were injected with SalB (22.5 mg x kg(-1)) in vena caudalis at 30 min before the experiment. In Nim-collated group, Nim (0.03 mg x kg(-1)) was injected into tail vein at the same time, while the mice in Sham-operated group and cerebral ischemia group were injected the same volume normal saline. The acute cerebral ischemia model was established by ligating bilateral common carotid arteries for 30 min in mice, then the mice were killed and the content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphocreatine (PCr) were observed, and the cerebral energy charge (EC) was computed. At the same time, activity of Na(+) -K(+) -ATPase and Ca2(+) -ATPase, content of water in brain tissue were measured.</p><p><b>RESULT</b>Compared with cerebral ischemia group, EC and content of ATP, ADP, PCr in SalB-treated group heightened evidently (P < 0.01). Moreover, activity of Na(+)-K+ ATPase and Ca2+ ATPase in SalB-treated group had a remarkable increase (P < 0.01). But the content of water in brain tissue decreased markedly (P < 0.05).</p><p><b>CONCLUSION</b>The mechanism that SalB can relieve content of water in brain tissue of cerebral ischemia in mice, may be associated with improving the content of high-energy phosphoric acid compounds and enhancing the activity of ATPase.</p>

Effect of salvianolic acid B on brain energy metabolism and hydrocephalus of cerebral ischemia in mice at different time / 药学学报

Mice pathological model of acute cerebral ischemia was established. In order to observe the effect of salvianolic acid B (Sal B) on brain energy metabolism and hydrocephalus in the brain of mice at different ischemic times, the energy charge (EC), content of phosphocreatine (PCr), level of lactic acid (Lac), activity of Na+ -K+ -ATPase, brain index and water content of brain were measured at 6, 12, 18, 24, and 30 min, separately after ligating bilateral common carotid arteries in mice. NIH mice were randomly divided into sham-operated group (sham), cerebral ischemia group (ischemia), Sal B-treated group (Sal B) and nimodipine-collated group (Nim). At 6 min after cerebral ischemia, EC, content of PCr and activity of Na +-K -ATPase began to decrease, while level of Lac, brain index and water content of brain increased gradually. However, Sal B (22.5 mg x kg(-1) improved pathophysiological changes at different ischemic times. Especially at 30 min after cerebral ischemia in Sal B group, EC (P < 0.01), content of PCr (P < 0.01 and activity of Na+ -K+ -ATPase ( < 0.05) increased significantly. Meanwhile, level of Lac (P < 0.01, brain index (P < 0.01) and water content of brain (P < 0.05) were lower obviously than those of cerebral ischemia group. Sal B could alleviate hydrocephalus by the improvement of energy metabolism in mice with acute cerebral ischemia, that provides scientific evidence that Sal B can be used for the clinical application of ischemic diseases.

Effects of naoreqing on secretive function of vaso-endothelial cells in rabbits with endotoxic fever / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the antifebrile effect of Naoreqing (NRQ) oral liquid on secretive function of vaso-endothelial cells in rabbits with endotoxic fever.</p><p><b>METHODS</b>Endotoxic fever rabbit model was duplicated to observe the effects of NRQ on body temperature, blood levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and endothelin (ET) using radioimmunoassay, as well as activity of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in plasma by chromophoric substrate assay.</p><p><b>RESULTS</b>Comparisons of various indexes between the two groups showed significantly difference, i.e. the maximal increment of body temperature: 0.69 +/- 0.07 degrees C vs 1.31 +/- 0.13 degrees C (the NRQ treated group vs the untreated model group, the same hereafter); 2h thermal response index TRI2 4.85 +/- 0.57 vs 8.44 +/- 0.98; plasma ET content 197.96 +/- 39.11 ng/L vs 250.80 +/- 40.99 ng/L; TXB2 content 177.35 +/- 77.30 ng/L vs 279.64 +/- 83.74 ng/L; activity of PAI 0.84 +/- 0.01AU/ml vs 0.86 +/- 0.01 AU/ml; plasma 6-keto-PGF1alpha content 986.70 +/- 327.36 ng/L vs 507.81 +/- 170.01 ng/L; activity of t-PA 0.25 +/- 0.02 IU/ml vs 0.21 +/- 0.02 IU/ml (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>NRQ may improve secretive function of vaso-endothelial cells to dilate blood vessel and quicken heat dissipation through body surface, so as to play an integral antipyretic effect in rabbits with endotoxic fever.</p>

Protective effect of jasminoidin on cascade of damage of cerebral ischemia in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the protective effect of jasminoidin on cascade of damage of cerebral ischemia.</p><p><b>METHOD</b>The rats were randomly divided into four groups: sham-operated group, ischemic group, the jasminoidin-treatment group and PNS-treatment group. Focal cerebral ischemia was produced by permanent occlusion of left middle cerebral artery (PMCAO) in rats. Radioimmunoassay (RIA) was utilized to identify the content of tumor necrosis factor-alpha (TNF-alpha) and interlukin 1beta (IL-1beta) in brain tissue of rats following ischemia. and that of Neuron-specific enolase (NSE) in rat's serum was observed too. The plasma concentration of vonWillebrand factor (vWF) was identified by enzyme-linked immunoadsordent assay (ELISA).</p><p><b>RESULT</b>After 12 h and 24 h of ischemia, the contents of TNF-alpha and IL-1beta and vWF as well as on NSE showed concomitant increase. Jasminoidin dramatically inhibited the increase of TNF-alpha and IL-1beta after 12 h and 24 h of ischemia, and repressed the increase of vWF after 12 h and 24 h of ischemia too. However, the influence of jasminodin NSE after 12 h and 24 h of ischemia was not significant.</p><p><b>CONCLUSION</b>Jasminoidin had good effect on repressing the expression of TNF-alpha and IL-1beta as well as vWF caused by cerebral ischemia, thus it manifested the effect of relieving the damage to vascular endothelial cell and blocking the progress of cascade damage of cerebral ischemia through inhibiting the process of inflammation.</p>