Exploring the common mechanism of Yindan Xinnaotong soft capsule in the treatment of stroke and coronary heart disease through HIF1α-MMP9-mediated HIF1α signaling pathway / 药学学报

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

Molecular Mechanism of Erzhiwan in Inhibiting Benign Prostatic Hyperplasia Base on Network Pharmacology / 中国实验方剂学杂志

Objective: To explain the "multi-components, multi-targets, multi-pathways" mechanism of Erzhiwan in treating benign prostatic hyperplasia(BPH) based the network pharmacology. Method: Ingenuity pathway analysis(IPA) was used to construct components-targets-diseases network and PPI network, then the classified enrichment analysis of gene ontology (GO) and pathway enrichment analysis (KEGG) were carried out on the main function of its gene sets, so as to discuss the mechanism of Erzhiwan in the treatment of BPH. Result: Erzhiwan has 19 components in IPA; and apigenin,luteolin,oleanolic acid and quercitrin were common components of Ligustri Lucidi Fructus and Echiptae Herba and the main component of Erzhiwan. Muscarinic acetylcholine receptor M3 (CHRM3), muscarinic acetylcholine receptor M2 (CHRM2), urokinase plasminogen activator receptor (PLAUR), kinin releasing enzyme 3 (KLK3), cadherin 1 (CDH1), chemokines 3 (CCL3) and metalloproteinase-1 (MMP-1) were important targets for Erzhiwan to treat BPH. The target proteins in PPI network were enriched with 20 GO functions and 5 main KEGG pathways, and Docking was verified for relevant targets. Conclusion: Erzhiwan may play a role in treating BPH by activating MMP-1 and inhibiting KLK3 and CCL3 protein expressions, inducing apoptosis, inhibiting cell proliferation and intervening relevant pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK) and nuclear factor(NF)-κB(NF-κB).

Socket shield technique for peri-implant tissue preservation in esthetics zone / 中国组织工程研究

BACKGROUND: Absorption of the alveolar bone subsequent to tooth extraction is a long-term process, especially in the anterior tooth region where the buccal part of the ridge undergoes a prominent remodeling process after tooth extraction. Socket shield technique (SST) recently reported may be a new choice for peri-implant tissue preservation. OBJECTIVE: To give an overview on the principle, interface basis and application of SST in implant dentistry. METHODS: The first author searched the PubMed, Ovid, CNKI, VIP and WanFang databases for relevant articles published from January 1990 to October 2017. The keywords were "socket shield technique;root-membrane technique; root-implant; implant proximity to teeth; dental-contected implants; dentointegration;cementum formation on implant surface" in Chinese and English, respectively. RESULTS AND CONCLUSION: SST aims to maintain alveolar bone and gingival tissues by preserving partial tooth root with its periodontium-bundle bone intact, which is an alternative strategy for tissue preservation in esthetics zone.

Development and application of component-based Chinese medicine theory / 中国中药杂志

Traditional Chinese medicine (TCM) prescription is the main therapies for disease prevention and treatment in Chinese medicine. Following the guidance of the theory of TCM and developing drug by composing prescriptions of TCM materials and pieces, it is a traditional application mode of TCM, and still widely used in clinic. TCM prescription has theoretical advantages and rich clinical application experience in dealing with multi-factor complex diseases, but scientific research is relatively weak. The lack of scientific cognition of the effective substances and mechanism of Chinese medicine leads to insufficient understanding of the efficacy regularity, which affects the stability of effect and hinders the improvement of quality of Chinese medicinal products. Component-based Chinese medicine (CCM) is an innovation based on inheritance, which breaks through the tradition of experience-based prescription and realize the transformation of compatibility from herbal pieces to components. CCM is an important achievement during the research process of modernization of Chinese medicine. Under the support of three national "973" projects, in order to reveal the scientific connotation of the prescription compatibility theory and develop innovative Chinese drugs, we have launched theoretical innovation and technological innovation around the "two relatively clear", and opened up the research field of CCM. CCM is an innovation based on inheritance, breaking through the tradition of experience based prescription, and realizing the transformation from compatibility of herbal pieces to component compatibility, which is an important achievement of the modernization of traditional Chinese medicine. In the past more than 10 years, with the deepening of research and the expansion of application, the theory and methods of CCM and efficacy-oriented compatibility have been continuously improved. The value of CCM is not only in developing new drug, more important is to build a communication bridge between traditional Chinese medicine and modern science and construct the system of key technologies which meet the need of innovation and development of TCM. This paper focused on the research progress, related concepts and technology development of CCM, as well as its application prospect in the theory research of Chinese medicine, development of innovative Chinese drugs, secondary development of Chinese patent medicine and upgrading of pharmaceutical technology.

Effect of valproic acid on inflammatory response after traumatic brain injury in rats / 中华急诊医学杂志

Objective To investigate the effects and mechanisms of valproic acid on brain edema,neurobehavioral outcome and inflammatory response after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Fifty-four SD male rats,weighting 220-250 g,were randomly divided into 3 groups (n =18):sham operation group (group sham),traumatic brain injury group (group TBI) and valproic acid treatment group (group TBI + VPA).Experimental rats were treated with valproic acid (300 mg/kg,twice daily) by intraperitoneal injection.Rat behavioral outcomes were measured by modified neurologic severity score (mNSS) tests at day 1,3,and 7 after TBI.Brain water content was measured with wet-dry weight method.The blood cells infiltration into cerebral cortex were tested with immunohistochemistry staining against ED-1 for macrophage.Inflammatory cytokines (INF-γ,tumor necrosis factor-α,interleukin-6) were measured by Western blotting.The statistical analysis were performed by ANOVA and chi-square tests using the statistical software program SPSS 13.0.Results Compared with the Sham group,the levels of brain edema,mNSS and macrophage cell infiltration were significantly increased after TBI (all P =0.00).The expressions of inflammatory cytokines were also increased significantly (all P =0.00).Compared with the TBI group,TBI + VAP group had significantly lower brain water content[3day:(80.12 ±0.59)％ vs.(82.14 ±0.67)％,P=0.04;7day:(74.74 ±0.72)％ vs.(77.93 ±0.48)％,P=0.01],and mNSS scores [3 day:(10.53 ±0.32) vs.(11.74 ±0.48),P =0.02;7 day:(7.97 ± 0.32) vs.(10.73 ± 0.42),P =0.01].VPA suppressed macrophage cell infiltration into cerebral cortex [(36.44 ± 0.72) ％ vs.(25.93 ± 0.48) ％ P =0.00].Meanwhile,VPA inhibited the expressions of inflammatory cytokines (INF-γ,TNF-α,IL-6) (P ＜ 0.05).Conclusions Treatment with VPA markedly reduced brain edema and improved neurological outcomes after TBI,possibly mediated by inhibited TBI-induced cerebral inflammatory responses and macrophage cell infiltrating into cerebral cortex.

Determination of 240 Pu/ 239 Pu in Plutonium-containing Particle by Laser Ablation Multiple Collector Inductively Coupled Plasma Mass Spectrometry / 分析化学

The isotopic fingerprints of plutonium are extremely important for nuclear safeguards and nuclear forensics. An analytical method was developed for direct determination of 240 Pu / 239 Pu ratio in plutonium-containing particles by laser ablation multiple collector inductively coupled plasma mass spectrometry ( LA-MC-ICP-MS). The risk of ablated particles leakage was reduced by leak detection, exhaust hood, and swiping the laser cell. Scanning mobility particle sizer (SMPS) was used to measure the effect of ablation parameters on the size distribution of ablated particles. The results showed that the majority of ablation material presented as particles from 40 -500 nm and the sweep time after laser ablation should be longer than 15 min. The particle size was evaluated to guide LA-MC-ICP-MS system. By using external normalization method for correction of the mass fractionation correction factor and ion counter efficiencies measured by nebulizer-coupled MC-ICP-MS, a LA-MC-ICP-MS method was established for analysis of 239 Pu / 240 Pu ratio in plutonium particles. Spot size, ablation rate and laser dwell time were set at 30 μm, 5 Hz and 5 s, respectively. Laser energy density was controlled to ensure that the intensities of 239 Pu for plutonium-containing particles were about 2×104 cps and 2×105 cps, respectively. The analytical results showed that the relative uncertainties for 239 Pu / 240 Pu was less than 1. 4% ( n = 6), and the measured value deviated by less than 4. 7% from the reference value. The time for adjusting system and determining 239 Pu / 240 Pu ratio in single plutonium particle was 9 h and 0. 5 h, respectively. The results demonstrated that this technique was rapid, precise and accurate, and could be used for determination of 239 Pu / 240 Pu in plutonium-containing particles.

Bidirectional regulation of angiogenesis by phytoestrogens through estrogen receptor-mediated signaling networks / 中国天然药物

Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERα and ERβ by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERα and ERβ were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERα, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERβ, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERα and ERβ may be critical in the balance of pro- or anti-angiogenesis process.

Cultivation and Biological Characterization of Chicken Primordial Germ Cells

The purpose of this work was to investigate the isolation, culture process of chicken gonadal primordial germ cells (PGCs) and study their biological characterization. PGCs were harvested from 5.5-day-old chicken embryonic genital ridges and explanted onto chicken embryonic fibroblasts (CEFs). The results showed that the primary cultivation of chicken PGCs on their own gonadal stroma cells were better than CEFs at first two days for reproduction. The conditioned media supported the growth and colony formation of PGCs for a prolonged time in vitro and maintained a normal diploid karyotype, which were positively stained by alkaline phosphatase (AKP), periodic acid Schiff (PAS) and reacted with anti-SSEA-1, SSEA-3, Oct4, Blimp1 and Sox2. Real-time PCR showed that they expressed the stage specific genes CVH, Blimp1 and Dazl, the stem cell specific genes Sox2, Pouv and Nanog. They also formed the embryoid bodies (EBs). These results suggested that the chicken PGCs cultured in vitro not only had strong self-renewal ability, but also had the potential capability of multi-lineage differentiation.

Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis / 药学学报

Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1β) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1β), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS.

Yang-tonifying traditional Chinese medicinal plants and their potential phytoandrogenic activity / 中国天然药物

The concept of phytoandrogens, plants that contain androgens or those that stimulate androgenic activity in men, is relatively new. In traditional Chinese medicine a number of phytoandrogens are classified in medicinal plant restoratives for reinforcing yang, and they find their application in the treatment of the kidney yang deficiency diseases. In this review, the phytoandrogens used in traditional Chinese medicine are listed, and their proven applications in the treatment of kidney yang deficiency diseases, such as sexual disorders, cancer, and obesity and associated metabolic syndromes are presented. As a background, the mechanism of action of androgens, their synthesis and metabolism, the interrelations of androgens and estrogens, as well as the state of art methods to detect and analyze these hormonal activities in medicinal plants are discussed.

Advance in study on endogenous formaldehyde and pathogenesis of Alzheimer's disease / 中国中药杂志

The injury of exogenous formaldehyde and its merchanism have attracted wide attention from researchers. The latest study found that mammals have a whole system for generating and clearning formaldehyde. However, the imbalance on the system for generating and clearning formaldehyde for various reasons will cause abnormal accumulation of endogenous formaldehyde in vivo, which is closely related to learning diability and memory dysfunction. The increase in endogenous formaldehyde concentration may be one of factors inducing such neurodegenerative diseases as Alzheimer's disease. The study on the relationship between endogenous formaldehyde and such neurodegenerative diseases as Alzheimer's disease is of great significance and can provide new thoughts for preventing and treating Alzheimer's disease with traditional Chinese medicines.

VEGF Pathway-targeted Therapy for Advanced Renal Cell Carcinoma: A Meta-analysis of Randomized Controlled Trials / 华中科技大学学报（医学）（英德文版）

Immunotherapy which has been in practice for more than 20 years proves effective for the treatment of metastatic renal cell carcinoma (mRCC).Anti-angiogenesis-targeted therapy has recently been identified as a promising therapeutic strategy for mRCC.This study was aimed to evaluate the effectiveness of vascular endothelial growth factor (VEGF) pathway-targeted therapy for mRCC by comparing its effectiveness with that of immunotherapy.The electronic databases were searched.Randomized controlled trials (RCTs) on comparison of VEGF inhibiting drugs (sorafenib,sunitinib and bevacizumab) with interferon (IFN) or placebo for mRCC treatment were included.Data were pooled to meta-analyze.A total of 7 RCTs with 3451 patients were involved.The results showed that anti-VEGF agents improved progression-free survival (PFS) and offered substantial clinical benefits to patients with mRCC.Among them,sunitinib had a higher overall response rate (ORR) than IFN (47％ versus 12％,P＜0.000001).Bevacizumab plus IFN produced a superior PFS [risk ratio (RR):0.86,95％ confidence interval (CI):0.76-0.97; P=0.01] and ORR (RR:2.19; 95％ CI:1.72-2.78; P＜0.00001) in patients with mRCC over IFN,but it yielded an increase by 31％ in the risk of serious toxic effects (RR:1.31; 95％ CI:1.20-1.43; P＜0.00001) as compared with IFN.The overall survival (OS) was extended by sorafenib (17.8 months) and sunitinib (26.4 months) as compared with IFN (13 months).It was concluded that compared with IFN therapy,VEGF pathway-targeted therapies improved PFS and achieved significant therapeutic benefits in mRCC.However,the risk to benefit ratio of these agents needs to be further evaluated.

Effects of Panax Notoginoside on the Expression of TGF-β1 and Smad-7 in Renal Tissues of Diabetic Rats / 华中科技大学学报（医学）（英德文版）

In order to explore the effects of Panax notoginoside (PNS) on the expression of transforming growth factor β1 (TGF-β1) and Smad-7 in renal tissues of diabetes,a rat model of diabetic nephropathy was set up by intravenous injection of streptozotocin (STZ).Wistar rats were randomly divided into normal group,diabetic control group,group treated by PNS at low-dosage (PL),group treated by PNS at high-dosage (PH) and group treated by catopril (C),respectively.Fasting blood glucose (FBG),renal index,endogenous creatinine clearance rate (Ccr) and urinary albumin (UAlb) in 24 h were examined after 6 weeks.Meanwhile,the expressions of TGF-β1 and Smad7 in renal tissues were immunohistochemically dectected.At the end of the sixth week,FBG,renal index,Ccr,UAlb were all elevated significantly in control group (P＜0.01).The expression of TGF-β1 protein was increased while Smad7 protein decreased in renal tissue (P＜0.01).However,the treatment with PNS reversed the aforementioned changes in renal tissues of diabetic rats.These results indicate that PNS possess a protective effect on the kidney of diabetic rats and it might protect kidney by inhibiting the expression of TGF-β1 protein and enhancing the expression of Smad7 protein.

Retroperitoneoscopic Microwave Ablation of Renal Hamartoma:Middle-term Results / 华中科技大学学报（医学）（英德文版）

The safety and efficacy of retroperitoneoscopic microwave ablation (MWA) in the treatment of renal hamartoma were evaluated. From July 2007 to July 2009, a total of 16 cases of renal hamartoma were treated with retroperitoneoscopic MWA. Peri- and post-operative findings were observed. Middle-term efficacy was assessed by contrast-enhanced computerized tomography (CT) in follow-up period. All patients received MWA of 1-5 points. The mean operative time was 85 min and the mean blood loss was 65 mL. During a median follow-up of 16 months, no evidence of disease recurrence was observed despite of incomplete ablation in 1 case. Retroperitoneoscopic MWA is a relatively simple procedure with less impact to renal function and less complication. The outcome of middle-term follow-up is satisfactory. Thus, retroperitoneoscopic MWA appears to be a safe and effective technique for renal hamartoma in selected patients.

Application of flow cytometry to detect cell apoptosis / 中国组织工程研究

Flow cytometry (FCM) is a technology for fast qualitation, quantitative analysis and separation of single cells or other biological particles. The method is rapid, sensitive and accurate, and its objective and direct result can be analyzed with multi-parameters simultaneously. The morphological, biochemical and molecular changes during apoptosis include cellular shrinkage, permeability transition of plasma membrane, caspases activation, dissipation of mitochondrial trans-membrane potential, phosphatidylserine redistribution, calcium flux and DNA fragmentation and content. The review outlined the methods to characterize, identify and quantify apoptoUc cells by flow cytometry to further determine cell apoptosis.

Marketing License System of Drugs at Home and Abroad:A Comparative Study / 中国药房

OBJECTIVE:To provide reference for the evolvement of the current drug marketing license system in China. METHODS: The registry classification, the drug registration procedure and the combination of marketing license and production license both at home and abroad were analyzed comparatively. In addition, the necessity and feasibility of the drug marketing license system in China were analyzed. RESULTS & CONCLUSIONS: The current drug marketing license system that centered on license No. goes against the investigation of legal ability, drug administration mode, medicine technology transfer system and original equipment manufacture thus remains be reformed. There is still difficulty for the enforcement of drug marketing licensor system, yet it should be carried out step by step until its establishment.