Effect of Shenfu Yixin Granules on Mitochondrial Dynamics in Rats with Heart Failure After Myocardial Infarction / 中国实验方剂学杂志

ObjectiveTo prepare a rat model of heart failure after myocardial infarction by ligation of the anterior descending branch of the left coronary artery， and to observe the effect of Shenfu Yixin granules on the mitochondrial dynamics of rats with heart failure. MethodFifty SD male rats were randomly taken ten as the sham operation group and the rest as modeling group. The rat model of heart failure after myocardial infarction was prepared by ligation of anterior descending branch of left coronary artery. According to the left ventricular ejection fraction（LVEF） on the 28th day after operation， the model rats were randomly divided into the model group， Shenfu Yixin granule low-dose and high-dose groups（3.011， 15.055 g·kg-1） and sacubitril valsartan sodium group（20.83 mg·kg-1）. Each administration group was gavaged daily with the corresponding dose of drug solution， while the sham operation group and model group were given the same amount of normal saline once a day for 28 days， with 6 rats in each group. Ultrasound was used to detect the cardiac function parameters， rat heart mass and body mass were weighed to calculate the cardiac mass index， enzyme linked immunosorbent assay（ELISA） was used to detect serum brain natriuretic peptide（BNP） and soluble growth stimulation expressed gene 2 protein（sST2） levels. Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of the myocardium. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expression of mitochondrial fusion protein 1/2（Mfn1/2）， optic atrophy protein 1（Opa1）， dynamin-related protein 1（Drp1） and fission protein 1（Fis1）. ResultCompared with the sham operation group， the mRNA and protein expression of LVEF， Mfn1， Mfn2， Opal in the model group decreased（P<0.05）， while BNP， sST2， cardiac mass index， Drp1， Fis1 mRNA and protein levels increased（P<0.05）. Compared with the model group， the expression of LVEF， Mfn1， Mfn2， Opal mRNA and protein increased in Shenfu Yixin granule high-dose and sacubitril valsartan sodium groups（P<0.05）， while BNP， sST2， cardiac mass index， Drp1， Fis1 mRNA and protein levels decreased（P<0.05）. Pathological observation showed that compared with the sham operation group， the model group had disordered arrangement of myocardial cells， inflammatory cell infiltration and myocardial fibrosis. Compared with the model group， the degree of inflammatory cell infiltration， myocardial or interstitial fibrosis was improved and alleviated in all administered groups. ConclusionShenfu Yixin granules can resist heart failure， reduce cardiac mass index， decrease BNP and sST2 contents， and improve cardiac function. Its mechanism may be related to the adjustment of mitochondrial dynamics.

Effect of Xintongtai Regulating p38 MAPK/AP-1 on Traditional Chinese Medicine Syndrome Score and Collagen Fibers in VSMCs of Rabbits with Atherosclerosis： An Exploration Based on Theory of Heart Receiving Qi From Spleen / 中国实验方剂学杂志

Objective:To explore the effects of Xintongtai （XTT） on traditional Chinese medicine （TCM） syndrome score and collagen fibers in vascular smooth muscle cells（VSMCs） of rabbits with atherosclerosis in the regulation of p38 mitogen-activated protein kinase （p38 MAPK）/activator protien-1 （AP-1）signaling pathway. Method:A total of 120 rabbits of SPF grade were randomly divided into the sham operation group， combined phlegm and blood stasis model group， rosuvastatin group， and low-， middle-， and high-dose XTT groups. The rabbit model of atherosclerosis due to combined phlegm and blood stasis was established by exposing them to high-fat diet and balloon injury. Following modeling， the corresponding drugs were administered by gavage for eight weeks （2.3， 4.6， 9.2 g·kg^-1 for low-， middle-， and high-dose XTT groups and 0.55 mg·kg^-1for rosuvastatin group）. At the end of medication， the abdominal aorta was isolated and stained with htoxylin-eosin （HE） for observing the vulnerable plaque. Matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） were detected by immunohistochemistry （IHC）. The collagen fiber decomposition in VSMCs was observed after Masson staining. The protein expression levels of p38 MAPK and AP-1 in aorta was assayed by Western blotting. The combined phlegm and blood stasis syndrome was scored based on TCM syndrome scoring scale. Result:Compared with the model group， XTT at each dose and rosuvastatin significantly decreased MMP-9 content， increased TIMP-1， down-regulated p38 MAPK protein expression， and weakened the nuclear translocation of AP-1 （<italic>P</italic><0.01）. Compared with the low-dose XTT group， the middle- and high-dose XTT groups and rosuvastatin group exhibited obviously lowered MMP-9，elevated TIMP-1， down-regulated p38 MAPK protein expression， and diminished AP-1 nuclear translocation （<italic>P</italic><0.05，<italic>P</italic><0.01）. The TCM syndrome scores of the middle- and high-dose XTT groups and rosuvastatin group were significantly improved as compared with that in the model group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The comparison with the low-dose XTT group revealed a remarkable improvement in TCM syndrome score of the middle- and high-dose XTT groups and rosuvastatin group （<italic>P</italic><0.01）. As demonstrated by Masson staining， the smooth muscle fibers in the model group were arranged in disorder， accompanied by enhanced collagen decomposition， thinned fibrous cap， and increased plaque vulnerability. Compared with the model group， the VSMCs in each XTT group and rosuvastatin group were orderly arranged， manifested as decreased collagen fiber decomposition and increased plaque stability. Conclusion:XTT down-regulates the expression of p38 MAPK and MMP-9， increases the level of TIMP-1， reduces the nuclear translocation of AP-1， diminishes the decomposition of collagen fibers in VSMCs， and improves the score of combined phlegm and blood stasis syndrome. XTT alleviates arteriosclerosis due to combined phlegm and blood stasis by regulating p38 MAPK/AP-1 signaling pathway and downstream cytokines and stabilizing vulnerable plaques.

Effect of TRPV4 on angiotensin II-induced renal injury in mice / 中国比较医学杂志

Objective This study was designed to determine the effect of transient receptor potential vanilloid type 4(TRPV4)on angiotensin Ⅱ(Ang Ⅱ)-induced renal injury in TRPV4-null mutant(TRPV4 -/-)mice. Methods The mice were divided into sham group and Ang Ⅱ-treated group. Ang Ⅱ was infused systemically into wild type(WT)and TRPV4 -/- mice via a miniosmotic pump for 4 weeks, and the sham mice were given with normal saline. Systolic blood pressure,urinary excretion of albumin and 8-isoprostane, serum creatinine, and the pathological changes in the kidney tissues were assayed after the 4-week treatment. Results Compared with corresponding sham mice,Ang Ⅱ infusion led to enhanced systolic blood pressure,increased urinary excretion of albumin and 8-isoprostane,increased serum creatinine(P< 0.05),and enhanced glomerulosclerosis degree and renal tubulointerstitial injury index(P< 0.05)in the WT and TRPV4 -/- mice. The result were associated with enhanced collagen levels in the kidney(P< 0.05). All of them were attenuated by the deletion of TRPV4 in the absence of alteration in blood pressure(P< 0.05). Conclusions Deletion of TRPV4 could alleviate renal injury during Ang Ⅱ-induced hypertension, suggesting that TRPV4 may contribute to the pathophysiology of angiotensin Ⅱ-induced renal injury.

Melatonin Augments the Effects of Fluoxetine on Depression-Like Behavior and Hippocampal BDNF-TrkB Signaling / 神经科学通报·英文版

Depression is a debilitating psychiatric disorder with a huge socioeconomic burden, and its treatment relies on antidepressants including selective serotonin reuptake inhibitors (SSRIs). Recently, the melatonergic system that is closely associated with the serotonergic system has been implicated in the pathophysiology and treatment of depression. However, it remains unknown whether combined treatment with SSRI and melatonin has synergistic antidepressant effects. In this study, we applied a sub-chronic restraint stress paradigm, and evaluated the potential antidepressant effects of combined fluoxetine and melatonin in adult male mice. Sub-chronic restraint stress (6 h/day for 10 days) induced depression-like behavior as shown by deteriorated fur state, increased latency to groom in the splash test, and increased immobility time in the forced-swim test. Repeated administration of either fluoxetine or melatonin at 10 mg/kg during stress exposure failed to prevent depression-like phenotypes. However, combined treatment with fluoxetine and melatonin at the selected dose attenuated stress-induced behavioral abnormalities. Moreover, we found that the antidepressant effects of combined treatment were associated with the normalization of brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the hippocampus, but not in the prefrontal cortex. Our findings suggest that combined fluoxetine and melatonin treatment exerts synergistic antidepressant effects possibly by restoring hippocampal BDNF-TrkB signaling.

Metabolomics analysis of Tripterygium wilfordii formulation based on theory of detoxicity compatibility / 中国中药杂志

Tripterygium wilfordii Hook. f. induced-hepatotoxicity was the main limitation for its usage in clinic. Qingluo Tongbi formulation showed obvious attenuation for hepatotoxicity in clinic and fundamental research in vivo. To explore the potential mechanism of the attenuation, we conducted a study on the plasma metabolomic profiles of T. wilfordii and Qingluo Tongbi formulation in rats by a sensitive gas chromatography-mass spectrometry (GC-MS/MS) method. In plasma samples, a total of 72 compounds were analyzed by EI source MS, and were successfully identified by matching NIST database. The semi-quantification results were then calculated by OPLS-DA model with SIMCA-P 13.0 software. The three groups were clearly distinguished in OPLS-DA score plot. In addition, the observation values of Qingluo Tongbi formulation showed the obvious trend towards the control levels, suggesting the detoxicity effect of the formulation. Variation metabolites were further analyzed by VIP and One Way ANOVAs, and the results showed a significant increase in compounds of glycogenic amino acids, such as alanine, proline, serine and glutamine after the administration of T. wilfordii, indicated that the tissue proteins were decomposed and amino acids were leakage into blood. Qingluo Tongbi formulation could reverse the amino acids into normal level. On the contrary, the levels of glucose, lactic acid and hydroxy butyrate decrease, and the formulation can relieve the disorder in the levels of lactic acid, suggesting the regulation of the energy metabolism. Additionally, the level of branched chain amino acid was decreased, suggested the toxicity was induced, but the formulation cannot increase it into the normal levels. Nevertheless, all the above results suggested that the classical Qingluo Tongbi formulation displayed the liver protection effect by adjusting the amino acid levels and regulating the energy metabolism. Qingluo Tongbi formulation was developed based on traditional Chinese medicine theory "detoxicity compatibility", and contained Panax notoginseng (Burk.) F. H. Chen to nourish blood and absorb clots. Modern pharmacology suggested that its liver protection effect was correlated with the promotion of protein synthesis. Another important herb is Rehmannia glutinosa Libosch., which can regulate the energy metabolism. Both were consistent with the metabolomic results in this study, which explained the potential mechanism of "detoxicity compatibility" theory. Therefore, the currently developed metabolomic approach and the obtained results would be highly useful for the comprehensive toxicity studies for other herbal medicines and various complex deoxicity formulations.

Effect of respiratory syncytial virus-related pulmonary infection on endogenous metabolites in large intestinal mucosa in mice / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of respiratory syncytial virus (RSV)-related pulmonary infection on endogenous metabolites in large intestinal mucosa in BALB/c mice using metabolomics technology based on gas chromatography-mass spectrometry (GC-MS).</p><p><b>METHODS</b>Mice were randomly divided into a control group and a RSV pneumonia model group (n=16 each). The mouse model of RSV pneumonia was established using intranasal RSV infection (100×TCID, 50 μL/mouse, once a day). After 7 days of intranasal RSV infection, the mice were sacrificed and GC-MS was used to identify endogenous metabolites and measure the changes in their relative content in colon tissue. SMCA-P12.0 software was used to perform principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) for endogenous metabolites in colon tissue. The differentially expressed metabolites in colon tissue were imported into the metabolic pathway platform Metaboanalyst to analyze related metabolic pathways.</p><p><b>RESULTS</b>PCA and OPLS-DA showed significant differences between the control and RSV pneumonia model groups. A total of 32 metabolites were identified in the colon tissue of the mice with RSV pneumonia. The RSV pneumonia model group had significant increases in the content of leucine, isoleucine, glycine, alanine, arachidonic acid, and lactic acid, which were related to the valine, leucine, isoleucine, arachidonic acid, and pyruvic acid metabolic pathways.</p><p><b>CONCLUSIONS</b>RSV pneumonia might cause metabolic disorders in the large intestinal tissue in mice.</p>

T1ρmagnetic resonance imaging for detection of early articular cartilage degeneration in knees of rabbit model treatment by Epimedium / 实用放射学杂志

Objective To explore the role of MRI(T1ρ)in the early osteoarthritis,curative efficacy monitoring and speculated that the mechanism of curative effect.Methods (1)(early OA model)A total of 28 New Zealand white rabbits were randomly divided into A,B,C three groups.group A(treatment)and B(control)were both for 1 1 rabbits,and 6 rabbits were considered as blank control group(group C).0.5 mL 1.6% papain was injected into the right knee joint cavity both group A and B according to three times (1,4,7 days).The equivalent dilution was injected into the left knee joint cavity simultaneously.3 weeks after the first injection,and T2 WI,3D-FS-SPGR,and T1ρ mapping in sagittal plain were scanned for three groups.Randomly selected two models pathology test in the group A and B,confirm early OA model is established.(2)(treat models)Then give epimedium lavage to group A two month.The equivalent sterile saline lavage to group B.A certain time (T0 = 0,T1 = 1 mon,T2 = 2 mon)after treated do MR scanned for group A and B.Analysis of the image.T1ρvalues and the cartilage thickness in bilateral femoral condyle cartilage were measured by post-processing software.The all femurs were pathological examined.T1ρvalues and the cartilage thickness were statistic analysis. Results (1)Articular cavity injection of papain can successfully establish early osteoarthritis rabbit model which pathology has been confirmed.T1ρvalues of the experimental (group A,B)were significant higher than of the control side(P0.05).(2)T1ρvalues of the Epimedium treat model (right side)were significant lower than of the pre-treatment that of the preintervention (P 0.05).Conclusion (1)T1ρvalues of the early and advanced stage of OA had increased in various degree,and the values related cartilage matrix composition.(2 )Single herb Epimedium has effective to treat early stages osteoarthritis in knee joint.Spec-ulated that the possible mechanism for treatment common channel in the development of OA,which inhibition protease formation and promote proteoglycan secretion.

Establishment and Management of Multicentral Collection Bio-sample Banks of Malignant Tumors from Digestive System / 中国医疗器械杂志

To establish and manage of multicentral collection bio-sample banks of malignant tumors from digestive system, the paper designed a multicentral management system, established the standard operation procedures (SOPs) and leaded ten hospitals nationwide to collect tumor samples. The biobank has been established for half a year, and has collected 695 samples from patients with digestive system malignant tumor. The clinical data is full and complete, labeled in a unified way and classified to be managed. The clinical and molecular biology researches were based on the biobank, and obtained achievements. The biobank provides a research platform for malignant tumor of digestive system from different regions and of different types.

Isolation, purification and activity identification of ABL tyrosine kinase and ABLT315I mutant / 中国生化药物杂志

Objective To establish a simple , stableand effective method for the isolation and purification of ABL tyrosine kinase and its mutant ABLT315I.Methods pET-28a vector was inserted in abl gene or its site directed mutagenesis.Then Escherichia coli BL21 competent cells were co-transformed with pGEX6P-1-ptp-1b and pET28a-abl/pET28a-ablc944t .The transformed BL21 cells were incubated, and then were stimulated with Isopropyl-β-D-thiogala-ctopyranoside ( IPTG ) to express ABL tyrosine kinase and its mutant .The ABL tyrosine kinase and its mutant was purified by affinity chromatography and gel filtration chromatography .SDS-PAGE was used to detect the purity and relative molecular weight of ABL tyrosine kinase and its mutant.BCA method was used to determine the concentration of ABL tyrosine kinase and its mutant .Finally, kinase activity of target protein was examined by ATP /NADH coupling method .ResuIts SDS-PAGE showed the high purity of ABL tyrosine kinase and its mutant.The concentration of ABL and ABLT 315I protein was reached 28mg/L of LB and 20mg/L of LB, respectively.Both of the target protein was measured to have good tyrosine kinase activity in vitro .ConcIusion A simple, stable and effective method for the isolation and purification of ABL tyrosine kinase and its mutant was found successfully in the study , which laying good foundation for High Throughput Drug Screening and structure analysis of protein subsequently .

Role of transient receptor potential vanilloid type 1 and C-C chemokine receptor 2 in renal injury induced by salt-sensitive hype / 中国医学科学院学报

<p><b>OBJECTIVE</b>To determine the effects of transient receptor potential vanilloid type 1 (TRPV1) channel ablation and a chemokine receptor 2 (CCR2) antagonist on salt-sensitive hypertension-induced renal injury.</p><p><b>METHODS</b>Wild-type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks with or without a CCR2 antagonist, RS504393 (n=8 for all the 4 groups). Sham WT and TRPV1(-/-) mice (both n=7) underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure, urinary excretion of albumin, 8-isoprostane and creatinine clearance for 24 hours were assayed during the experimental period and at the end of the 4-week treatment. The morphological analysis was performed in renal histological sections, including glomerulosclerosis, tubulointerstitial injury, and monocyte/macrophage infiltration.</p><p><b>RESULTS</b>Compared to the corresponding control mice, DOCA-salt treatment in both WT and TRPV1(-/-) mice led to increased systolic blood pressure (SBP), enhanced urinary excretion of albumin and 8-isoprostane, decreased creatinine clearance, increased glomerulosclerosis and tubulointerstitial injury associated with enhanced monocyte/macrophage infiltration (all P<0.05), all of which were much more severe in TRPV1(-/-) mice compared to WT mice with the exception of blood pressure (all P<0.05). RS5043943 attenuated DOCA-salt-induced changes in renal function and morphology in WT and TRPV1(-/-) mice (all P<0.05). There was no difference in blood pressure among DOCA-salt WT and TRPV1(-/-) mice with or without RS505393 with the exception of sham WT and TRPV1(-/-) mice (all P>0.05).</p><p><b>CONCLUSIONS</b>CCR2 antagonist inhibits DOCA-salt-induced renal injury and monocyte/macrophage infiltration in WT and TRPV1(-/-) mice with the greater in the latter strain. Activation of TRPV1 attenuates salt-sensitive hypertension-induced renal injury possibly via inhibition of CCR2-induced monocyte/macrophage infiltration.</p>

Design of a satisfaction evaluation indicator system based on patients' experience of medical services / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To construct a satisfaction evaluation indicator system based on patients' experiences of medical services.</p><p><b>METHODS</b>A questionnaire was designed by expert interview and literature review and 400 copies were randomly handed out to inpatients and outpatients from five 3A-public hospitals in Shanghai. The patient's evaluation of importance of various factors in medical services was analyzed and the mean and weight of indicators in terms of recognition, importance and evaluation were determined to establish a satisfaction evaluation indicator system.</p><p><b>RESULTS</b>A total of 396 valid questionnaires were retrieved, with an effective response rate of 99%. By analyzing survey data, the patient satisfaction evaluation indicator system was constructed with 5 primary indicators (hospital environment, medical procedures, attitude, and quality of care and patient rights) and 25 secondary indicators (convenient hospital environment, auxiliary facilities, reasonable arrangement, clearly mark, convenient appointment, simple procedures, short time, the attitude of medical staff, solutions of medical dispute, medical technology, treatment, medical equipment, medical expenses, respect, patient privacy, etc.).</p><p><b>CONCLUSION</b>A patient satisfaction evaluation indicator system has been established based on patients' experience of medical services in the study, which may be applicable to measure patients' satisfaction and to improve medical services in hospitals.</p>

Role of chemokine receptor 2 in renal damage induced by deoxycorticosterone acetate-salt hypertension / 中国医学科学院学报

<p><b>OBJECTIVE</b>To determine the role of chemokine receptor 2 (CCR2) in the development of salt-sensitive hypertension-induced renal damage.</p><p><b>METHODS</b>We investigated the renal damage induced by uninephrectomy and deoxycorticosterone acetate (DOCA)-salt in mice treated with or without a selective CCR2 antagonist RS504393 for 4 weeks. Sham mice underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure, urinary excretion of albumin and 8-isoprostane, creatinine clearance, glomerulosclerosis, renal tubulointerstitial injury, and renal monocyte/macrophage infiltration were measured.</p><p><b>RESULTS</b>DOCA-salt treatment led to increased systolic blood pressure, increased urinary excretion of albumin and 8-isoprostane, decreased creatinine clearance, glomerulosclerosis, renal tubulointerstitial injury, and renal monocyte/macrophage infiltration compared with the sham mice (P<0.05). All of them were prevented by CCR2 inhibition (P<0.05).</p><p><b>CONCLUSION</b>Blockade of CCR2 prevents renal damage induced by DOCA-salt treatment, suggesting that CCR2-mediated monocyte/macrophage infiltration may contribute to salt-sensitive hypertension-induced renal injury.</p>

Effects of Nourishing yin clearing heat (Chinese characters: see text) Chinese herbal medicine on vascular endothelial growth factor the epiphyseal cartilage of growth retardation / 中国骨伤

<p><b>OBJECTIVE</b>To observe the effects of Nourishing yin clearing heat ([Chinese characters: see text]) Chinese herbal medicine on vascular endothelial growth factor (VEGF) in growth retardation induced by Decamethasone and observe its mechanisms.</p><p><b>METHODS</b>Thirty one-month-old New Zealand white rabbits were randomly divided into normal group, dexamethasone-treated group and Nourishing yin clearing heat ([Chinese characters: see text]) Chinese herbal medicine-treated group. The rabbits in dexamethasone group and Nourishing yin clearing heat ([Chinese characters: see text]) Chinese herbal medicine-treated group received dexamethasone (5 mg/kg x d). The rabbits were sacrificed at the 6th and 12th week after administration, and then rabbit tibia articular was removed. (1) Using TUNEL stain to detect apoptotic index. (2) Using immunohistochemical stain to detect the positive index of the expression of vascular endothelial growth factor (VEGF) in the epiphyseal cartilage of growth. (3) Using fluorescent quantitative PCR to detect the expression intensity of VEGF mRNA in each group.</p><p><b>RESULTS</b>At the 6th and 12th week after administration, there were significant difference in apoptotic index and cell proliferation index between dexamethasone group and normal group (P<0.01, dexamethasone group more than normal group). Immunohistochemical stain and fluorescent quantitative PCR indicated that the expression of VEGF and VEGF mRNA in dexamethasone group was significantly decreased as compared with that in normal group (P<0.01), and also obviously lower than Chinese herbal medicine-treated group (P<0.01).</p><p><b>CONCLUSION</b>VEGF has 2. an important role during the growth retardation induced by Dexamethasone. Nourishing yin clearing heat ([Chinese characters: see text]) Chinese herbal medicine can reduce the growth retardation induced by Dexamethasone through increasing the VEGF expression in growth plate chondrocytes and then increase angiogenesis.</p>

Importance of nanobiology and nanomedicine / 中国医学科学院学报

Focused on nanobiology and nanomedicine, this article elucidates its main research targets and contents, discusses the important of researches in this field, introduces the tasks and objectives of the corresponding researches in the national long- and mid-term science and technology development planning, and also describes the present research status in China.