Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats / 中国结合医学杂志

OBJECTIVE@#To investigate whether the antihypertensive mechanism of electroacupuncture (EA) is associated with attenuating phenotype transformation of vascular smooth muscle cells (VSMCs) via phosphoinositide3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways.@*METHODS@#Eight Wistar-ktoyo (WKY) rats were set as normal blood pressure group (normal group). A total of 32 spontaneous hypertensive rats (SHRs) were randomly divided into 4 groups using random number tables: a model group, an EA group, an EA+PI3K antagonist group (EA+P group), and an EA+p38 MAPK agonist+extracellular signal-regulated kinase (ERK) agonist group (EA+M group) (n=8/group). SHRs in EA group, EA+P group and EA+M group received EA treatment 5 sessions per week for continuous 4 weeks, while rats in the normal and model groups were bundled in same condition. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) of each rat was measured at 0 week and the 4th week. After 4-week intervention, thoracic aorta was collected for hematoxylin-eosin (HE) staining, immunohistochemistry [the contractile markers α-smooth muscle actin (α-SMA) and calponin and the synthetic marker osteopontin (OPN)] and Western blot [α-SMA, calponin, OPN, PI3K, phosphorylated-Akt (p-Akt), Akt, p-p42/44 ERK, total p42/44 ERK, p-p38 MAPK and total p38 MAPK].@*RESULTS@#EA significantly reduced SBP, DBP and MAP (P<0.01). HE staining showed that the wall thickness of thoracic aorta in EA group was significantly decreased (P<0.01). From results of immunohistochemistry and Western blot, EA increased the expression of α-SMA and calponin, and decreased the expression of OPN (P<0.01). In addition, the expression of PI3K and p-Akt increased (P<0.01), while the expression of p-p42/44 ERK and p-p38 MAPK decreased in EA group (P<0.01). However, these effects were reversed by PI3K antagonist, p38 MAPK agonist and ERK agonist.@*CONCLUSIONS@#EA was an effective treatment for BP management. The antihypertensive effect of EA may be related with inhibition of phenotypic transformation of VSMCs, in which the activation of PI3K/Akt and the repression of MAPK pathway were involved.

Mechanism of Huangjing Qianshi Decoction in treatment of prediabetes based on network pharmacology and molecular docking / 中国中药杂志

This study analyzed the molecular mechanism of Huangjing Qianshi Decoction(HQD) in the treatment of prediabetes based on network pharmacology and molecular docking. The active components of HQD were identified and screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP, http://Lsp.nwu.edu.cn/tcmsp.php) and then the targets of the components and the genes related to prediabetes were retrieved, followed by identifying the common targets of the decoction and the disease. The medicinal component-target network was constructed by Cytoscape to screen key components. The protein-protein interaction(PPI) network was established by STRING and hub genes were identified by Cytoscape-CytoNCA, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) of the hub genes with R-clusterProfi-ler. Thereby, the possible signaling pathways were predicted and the molecular mechanism was deduced. A total of 79 active components of HQD and 785 diabetes-related targets of the components were screened out. The hub genes mainly involved the GO terms of tricarboxylic acid cycle, peptide binding, amide binding, hydrolase activity, and kinase activity regulation, and the KEGG pathways of AGE-RAGE signaling pathway, TNF signaling pathway, AMPK signaling pathway, IL-17 signaling pathway, and insulin signaling pathway. Western blot result showed that HQD-containing serum significantly reduced the expression of AKT1, AGE, and RAGE proteins in insulin resistance model cells. HQD's treatment of prediabetes is characterized by multiple pathways, multiple targets, and multiple levels. The main mechanism is that the components zhonghualiaoine, baicalein, kaempferol, and luteolin act on AKT1 and inhibit the AGE-RAGE axis.

Clinical Efficacy of Midified Wendantang and Xueyaping Recipe in Middle Aged and Young People with Hypertension and Phlegm Dampness Retention / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of modified Wendantang combined with Xueyaping recipe in the middle aged and young people with hypertension and syndrome of phlegm dampness accumulation， and investigate its effect on metabolism. Method:One hundred and twenty patients were divided into control group and observation group averagely. Patients in both groups got lifestyle intervention and bisoprolol maleate tablets， 5-10 mg/time， 1 time/day. Patients in observation group additionally took modified Wendantang combined with Xueyaping recipe， 1 dose/day. Patients in control group addiiotnally got placebo granules Banxia Tianma Wan， 6 g/time， 2 times/day. The treatment was continued for 12 weeks in both groups. Blood pressure was measured at home to measure the compliance rate of blood pressure during the treatment and after the treatment. Before and after treatment， 24 h mean systolic blood pressure （24 h SBP）， 24 h mean pulse pressure （24 h PP）， 24 h mean diastolic blood pressure （24 h DBP）， blood pressure variability （BPV） ［24 h systolic blood pressure standard deviation （24 h SSD）， 24 h diastolic blood pressure standard deviation （24 h DSD）， systolic blood pressure variation coefficient （nSCV）， and diastolic blood pressure variation coefficient （nDCV） were recorded，compare night coefficients］. Scores of syndrome of phlegm dampness accumulation， body mass index （BMI） and waist hip ratio （WHR） were evaluated. Levels of uric acid （UA）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterin （HDL-C）， low-density lipoprotein cholesterin （LDL-C）， fasting blood glucose （FBG） and fasting insulin （FINS）， insulin resistance index （HOMA-IR）， homocysteine （Hcy）， Cystatin C （CysC）， angiotensin Ⅱ （Ang Ⅱ） and nuclear factor kappa B （NF-<italic>κ</italic>B） were measured. In addition， the safety was evaluated. Result:Compliance rate of blood pressure in observation group was 94.74%（54/57）， higher than 80.70% （46/57） in control group （<italic>χ</italic>²=5.211， <italic>P</italic><0.05）. Levels of 4 h SBP， 24 h DBP， 24 h PP， 24 h SSD， 24 h DSD， nSCV， nDCV， Hcy， CysC， AngⅡ， and NF-<italic>κ</italic>B in observation group were all lower than those detected from control group （<italic>P</italic><0.01）. Score of syndrome of phlegm dampness accumulation was lower than that in control group （<italic>P</italic><0.01）. Levels of UA， TC， TG， LDL-C and HOMA-IR were lower than those in control group （<italic>P</italic><0.05）， while level of HDL-C was higher than that detected from control group （<italic>P</italic><0.05）. Conclusion:Based on lifestyle and western medicine intervention， Wendantang combined with Xueyaping recipe can further control the blood pressure level， reduce the symptoms of phlegm dampness retention syndrome， improve blood pressure variability， improve the compliance rate of blood pressure， improve the metabolism of patients and reduce the risk factors of ASCVD in middle aged and young people with hypertension.

Comparative Genomic Analysis of Enterovirus 71 Revealed Six New Potential Neurovirulence-associated Sites / 生物医学与环境科学（英文）

In the present study, the complete genomes of four common (4/EV71/Wenzhou/CHN/2014, 15/ EV71/Wenzhou/CHN/2014, 116/EV71/Wenzhou/ CHN/2014, and 120/EV71/Wenzhou/CHN/2014) and two virulent (11/EV71/Wenzhou/CHN/2014 and 109/EV71/Wenzhou/CHN/2014) enterovirus 71 (EV71) isolates were sequenced and described. They are 7405 bp in length and belong to EV71 sub-genotype C4 (C4a cluster). Nucleotide sequence alignment revealed six nucleotide variations (GP151→TP151, GP199→AP199, GP261→TP261, AP328→CP328, GP422→AP422, and GP437→TP437) in the two virulent isolates within the 5'UTR of the IRES element. RNA secondary structure predictions of IRES and FCE indicated that the common isolates shared similar structures, which were different from those of the virulent isolates. Moreover, the GP114→CP114 and GP151→TP151 mutations in the virulent isolates contributed to the formation of the unique RNA secondary structures in SL II. Furthermore, nucleotide/amino acid sequence alignments of 82 EV71 isolates indicated that six sites (TP488 and CP577 in the 5'UTR; AsnP57 in 2A; IleP56 in 3C; CP10 and AP47 in the 3'UTR) are potentially associated with the neurovirulence of EV71. Finally, the 3D structures of 2A were analogous, whereas the structures of VP1 and 3C were variable.

Analysis on the current use and trend of drugs for digestive system through comprehensive statistics index, in Hangzhou / 中华流行病学杂志

Objective To investigate the use and trend of drugs on digestive system in Hangzhou area, under the comprehensive statistics index (CSI). Methods Using the analytical method related to the sum of consumption and CSI, the application of digestive system drugs of different manufacturers in Hangzhou from 2005 to 2007 was analyzed. Results Other than H2 receptor antagonist, the total consumption of digestive system drugs increased yearly, in terms of the total consumption, the first 4 leading ones were proton pump inhibitors, micro ecology medicines, antiemetic drugs and gastroprokinetic agents. The Laspeyres index of drugs on digestive system increased to different extent. The Laspeyres indices of proton pump inhibitors, probiotics,antiemetic drugs and gastroprokinetic agents were 1.396 50, 1.020 42, 1.728 90, 1.148 50 in 2006 while 2.081 10, 1.217 55,2.223 50, 1.156 60 in 2007, respectively. Conclusion Through CSI, the results showed the situation of use and trend of digestive system related drugs in Hangzhou. Factors as rationality, efficiency and costs of the drugs as well as the etiology of the disease were also explored to some degree.

Synergistic effects of proteasome inhibitor and histone deacetylase inhibitor on apoptosis and aggresome formation in T lymphoma cells / 中国实验血液学杂志

The aim of the study was to explore the synergistic effect of the proteasome inhibitor bortezomib (bor) and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on apoptosis of T lymphoma cell lines Jurkat and Hut78, and on the formation of aggresome. Jurkat and Hut78 cells were treated with bor (10 nmol/L) or bor (10 nmol/L) combined with SAHA (2 micromol/L) respectively. Cell growth inhibition was estimated by trypan blue dye exclusion test. Cell morphology was evaluated by light microscopy with Wright's staining of cytocentrifuge preparations. Cell apoptosis was analyzed by flow cytometry. Ultrastructure of cell apoptosis and aggresome were observed by transmission electron microscopy. The results showed that proliferation of both Jurkat and Hut78 cells was significantly inhibited in the bor+SAHA group, as compared with the control group and the bor alone group. Flow cytometric analysis confirmed that the percentage of apoptosis in Jurkat and Hut78 cells in the bor+SAHA group (41.8+/-4.7% and 72.7+/-11.7% respectively) was remarkably higher than those in the control group (3.6+/-1.3% and 7.0+/-1.9% respectively) and the bor alone group (6.3+/-2.3% and 18.7+/-9.2% respectively) (p<0.01). Ultrastructure examination revealed that typical aggresomes in cells could be observed in bor alone group. The combination of bor and SAHA diminished both the amount and density of aggresomes, or even eliminated them, accompanied by the increased rate of apoptosis. It is concluded that proteasome inhibitor combined with histone deacetylase inhibitor synergically induces T lymphoma cell apoptosis. Bortezomib stimulates the formation of aggresome, while SAHA destroys this aggresome structure, which may be one of the mechanisms underlying the enhancement of bortezomib-induced apoptosis.

Effects of enantiomers(R,R)-XY and(S,S)-XY on ocular blood flow in rabbits / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To evaluate the effects of two series of enantiomers [(R, R)-XY-1 through (R, R)-XY-12 and (S,S)-XY-1 through (S, S)-XY-12] on ocular blood flow in rabbits.·METHODS; Colored microsphere technique was used for in vivo experiments to determine the ocular blood flow in various tissues of ocular hypertensive (40mmHg) rabbit eyes.·RESULTS; Of the twelve compounds of ( R, R)-XY series examined, four increased choroidal blood flow at 10g/L, 50uL instilled into eyes. All compounds of (S, S)-XY series were not effective on ocular blood flow.·CONCLUSION; Some compounds of (R, R)-XY series increased the ocular blood flow, which might be useful for the prevention and treatment of ocular blood flow related eye diseases. Among all twenty-four compounds, (R, R)-XY-1and (R, R)-XY-9 seem to be the most potent ones.KEYWORDS; ocular blood flow; ischemia; enantiomer