Molecular Mechanism of Jingfang Mixture Against H1N1 Influenza Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo predict the potential targets and mechanism of Jingfang mixture in the treatment of H1N1 influenza and provide references for clinical application of Jingfang mixture. MethodThe active components and targets of Jingfang mixture against H1N1 influenza were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），SwissTargetPrediction， and TargetNet. The targets of H1N1 influenza were obtained from GeneCards，Online Mendelian Inheritance in Man （OMIM）， and DisGeNET and standardized by UniProt KB. The intersection targets were obtained by Venny 2.1.0. The "drug-component-target" network was constructed with Cytoscape 3.2.1 and analyzed for the topological attributes. The intersection targets were uploaded to STRING 11.5 to obtain the protein-protein interaction （PPI） network. Gene Ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis were carried out by Metascape. Finally，the top active components ranked by degree were docked to the core targets by Autodock vina and visually analyzed by PyMOL. Balb/c female rats were used for experimental verification. Hematoxylin-eosin（HE） staining was used to observe the pathological changes in lung tissues. Enzyme-linked immunosorbent assay（ELISA）was used to detect the levels of tumor necrosis factor-α（TNF-α），interleukin-10（IL-10）， and interleukin-17（IL-17）. Real-time fluorescence-based quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels in lung tissues. ResultThere were 144 active components in Jingfang mixture. A total of 421 target genes of Jingfang mixture and 2 956 targets of H1N1 influenza were identified，including 199 common targets. Topological analysis showed that the core components of Jingfang mixture against H1N1 influenza included quercetin，luteolin， and kaempferol，and the core targets included prostaglandin-endoperoxide synthase 2（PTGS2），estrogen receptor alpha（ESR1），inducible nitric oxide synthase 2（iNOS2），peroxisome proliferator-activated receptorγ（PPARγ），and cyclooxygenase-1（PTGS1）. GO enrichment yielded 697 items in biological process （BP） （P<0.01）， 59 items in molecular function （MF）（P<0.01）， and 21 items in cellular component （CC） （P<0.01）. A total of 132 signaling pathways （P<0.01） were obtained by KEGG enrichment analysis， including phosphatidylinositol 3-kinases（PI3K）/protein kinase B（Akt） signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway，most of which were related to the regulation of immune inflammation. Molecular docking showed that the binding energy of the active components of Jingfang mixture to the core targets was less than -5.0 kcal·mol-1，indicating good binding activity. HE staining showed that the lung tissues were significantly improved after drug intervention，and Real-time PCR and Western blot showed that Jingfang mixture could reduce the mRNA and protein expression of PI3K and Akt in lung tissues. ConclusionJingfang mixture can play an anti-viral effect against the influenza A virus through multiple components，multiple targets， and multiple pathways. The active components quercetin，luteolin， and kaempferol may control the inflammation and regulate immunity on the PI3K/Akt，MAPK， and other signaling pathways by acting on targets such as PTGS2，ESR1，iNOS2，PPARγ， and PTGS1.

Effect of YU Ying-ao's Tongzhifang in Treatment of Epilepsy Based on Clinical Diagnosis and Treatment Data / 中国实验方剂学杂志

Objective:Analyze the composition of Tongzhifang，regularity of modified prescriptions based on outpatient medical records of national famous Chinese medicine practitioner Professor YU Ying-ao for the treatment of epilepsy as well as data mining， and summarize the clinical experience of Professor YU in diagnosis and treatment of epilepsy， in order to provide the reference basis for the traditional Chinese medicine treatment epilepsy. Method:Based on the data of outpatient medical records of Professor YU for epilepsy diagnosis and treatment，this study conducted standard patient follow-up，clinical data collection，pretreatment and mining analysis，and was confirmed through expert interviews. Liquorice 2.3 data mining platform and SPSS 17.0 were used for data management and statistical analysis. Result:A total of 1 219 medical records of 243 cases were completely collected. As a result， Professor YU Ying-ao's Tongzhifang for epilepsy was based on ancient prescription Baijinwan，in which Shenglongchi and Ostreae Concha enhance tranquilizing and hyperactivity-subduing effects，Citri Reticulatae Pericarpium，Armeniacae Semen Amarum，Arisaema Cum Bile and Bambusae Caulis in Taenias eliminate phlegm and free channels， Salviae Miltiorrhizae Radix et Rhizoma and Persicae Semen promote blood circulation to remove blood stasis， and the 10 herbs were meticulously composed and well compatible. According to the small sample data，the total effective rate of patients with tetany type epilepsy taking this prescription for 3 months and 6 months was 80% （P<0.01）， with no adverse reactions. As for the dosage of Tongzhifang，the dosage for adult pills is generally 3-6 times that of decoction prescriptions，and the dosage for children's pills is generally 5-10 times that of decoction prescriptions. Under the guidance of the combination of disease differentiation and syndrome differentiation，epilepsy at the acute phase was treated with additionally Hupomo 1.5-3 g，the ratio of Curcumae Radix to Alumen is usually 4∶1， severe convulsion was treated with additionally Uncariae Ramulus Cum Uncis， Bombyx Batryticatus and Pheretima， epilepsy due to trauma was treated with additionally Typhae Pollen， Eupolyphaga Steleophaga， Carthami Flos and Radix Paeoniae Rubra； constipation was treated with additionally Cannabis Fructus； fatigue was treated with additionally Astragali Radix； dyspepsia was treated with additionally Galli Gigerii Endothelium Corneum； and irritability treated with additionally Gentiana scabra Bunge. Conclusion:The composition of Professor YU's Tongzhifang for treating epilepsy with Qianzhen Zhixian Huatan Tongluo method is relatively stable. Modified prescriptions are based on syndrome differentiation. Clinical experience and dosage range of decoction prescription and pill prescription for adults and children are available.

Mechanisms of Toxicity and Cardiotoxicity of Alcohol Extract from Root, Stem and Leaf of Chloranthus Serratus / 法医学杂志

Objective To compare the differences of cardiotoxicity of alcohol extract from root, stem and leaf of Chloranthus serratus in the rats, and discuss preliminarily its mechanism of toxicity. Methods Rats were randomly divided into four groups: blank, root alcohol, stem alcohol and leaf alcohol, with 8 in each group. After 14 days of continuous intragastric administration, the body mass change curves were drawn. The cardiac coefficient was calculated. The contents of creatine kinase （CK）, creatine kinase isoenzyme （CK-MB）, lactate dehydrogenase （LDH） and α-hydroxybutyrate dehydrogenase （α-HBDH） as well as the content changes of oxidative stress indexes - total superoxide dismutase （T-SOD） and malondialdehyde （MDA） in the serum of rats were detected. The cardiac pathomorphology changes in the rats were observed. The expression of intercellular adhesion molecule （ICAM-1） and heme oxygenase （HO-1） in myocardial tissue was detected. Results Body mass growth rate： stem alcohol group was the smallest, followed by leaf alcohol group. The difference of cardiac coefficient of every group had no statistical significance （P>0.05）. The myocardial tissues of stem alcohol group suffered the most serious damage, followed by the leaf alcohol group. The contents of CK, CK-MB, LDH and α-HBDH in stem alcohol group increased （P<0.05）. The increase of MDA content and decrease of T-SOD content in stem alcohol group had statistical significance compared with the blank group and root alcohol group, while the leaf alcohol group only had statistical significance in the decrease of T-SOD content compared with the blank group （P<0.05）. The positive expression of ICAM-1 enhanced and the expression of HO-1 protein decreased in every group after the intervention of different extracts. The change trend was stem alcohol > leaf alcohol > root alcohol group. Conclusion The alcohol extract from the stem has the highest cardiotoxicity, followed by the leaf extract, and its mechanism of toxicity may be related to oxidative stress.

Research on antitumor active components and mechanisms of natural products / 药学学报

Tumor, especially malignant tumor has become one of the major diseases, a serious threat to the health of people around the world. Modern clinical practice shows that the natural active products extracted from traditional Chinese medicine, marine medicine and other natural drugs, such as terpenes, alkaloids, polysaccharides, volatile oils and peptides, can effectively inhibit the growth of tumor cells. In this paper, the active components of natural antitumor products in recent years were summarized and their related mechanism was elucidated, so as to provide theoretical basis for the further development of natural antitumor drugs.

Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.</p><p><b>METHODS</b>Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment.</p><p><b>RESULTS</b>The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465).</p><p><b>CONCLUSIONS</b>These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.</p>

Topic model for Chinese medicine diagnosis and prescription regularities analysis: case on diabetes / 中国结合医学杂志

Induction of common knowledge or regularities from large-scale clinical data is a vital task for Chinese medicine (CM). In this paper, we propose a data mining method, called the Symptom-Herb-Diagnosis topic (SHDT) model, to automatically extract the common relationships among symptoms, herb combinations and diagnoses from large-scale CM clinical data. The SHDT model is one of the multi-relational extensions of the latent topic model, which can acquire topic structure from discrete corpora (such as document collection) by capturing the semantic relations among words. We applied the SHDT model to discover the common CM diagnosis and treatment knowledge for type 2 diabetes mellitus (T2DM) using 3 238 inpatient cases. We obtained meaningful diagnosis and treatment topics (clusters) from the data, which clinically indicated some important medical groups corresponding to comorbidity diseases (e.g., heart disease and diabetic kidney diseases in T2DM inpatients). The results show that manifestation sub-categories actually exist in T2DM patients that need specific, individualised CM therapies. Furthermore, the results demonstrate that this method is helpful for generating CM clinical guidelines for T2DM based on structured collected clinical data.

Effect of ephedrine on neuronal plasticity in neonatal rats after hypoxic-ischemic brain injury / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of ephedrine on neural plasticity after hypoxic-ischemic brain damage (HIBD) in neonatal rats.</p><p><b>METHOD</b>Sixty SD rats, aged 7 days, were made as HIBD model, which were randomly divided into following 4 groups, an ephedrine group, a D-amphetamine (D-AMPH) group, a cytodine triphosphate-2Na (CTP) group and a ganglioside (GMI) group. Changes in the expression of growth-associated protein-43 (GAP-43) and synaptophysin (SYP) in the hippocampal area CA3 were detected with immunohistochemical method. Four weeks after the operation, learning and memory test in Morris water maze was performed for 5 days.</p><p><b>RESULT</b>(1) The GAP-43 and SYP expression levels in hippocampal area CA3 in the ephedrine group were higher than those in the spontaneous recovery group (P < 0.05), with no significantly different from those the CTP group and the D-AMPH group. (2) The average escape latency in the ephedrine group, the D-AMPH group and the CTP group were significantly shorter than that in the spontaneous recovery group (P < 0.05), and the frequency passing the original platform in the 3 treatment groups were significantly more than those in the spontaneous recovery group (P < 0.01). The escape latency was longer and the frequency passing the original platform was less in the ephedrine group than that in the GM1 group, with no significant differences as compared with the CTP group and the D-AMPH group.</p><p><b>CONCLUSION</b>Ephedrine can enhance spatial orientation and learning and memory abilities of HIBD rats in later life. This protective effect is associated with decrease of neuronal loss after HIBD, and promotion of the expression of GAP43 and SYP. Ephedrine can exert the same protection against HIBD as D-AMPH and CTP do, but the amelioration of spatial orientation and learning and memory abilities by ephedrine in later life in rats after HIBD is slightly weaker than that by GM1, which is possibly related with the dose of ephedrine.</p>

Effects of hyperbaric oxygenation on rabbits 'testes with varicocele / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the mechanism of male infertility caused by varicocele by evaluating the effects of hyperbaric oxygenation (HBO) therapy on the testicular tissue morphology and function of rabbit model with varicocele(VC).</p><p><b>METHODS</b>Twenty-four mature male rabbits were randomly divided into three groups: pseudo-operation, VC model and VC model administered by HBO. Experimental varicocele was induced by partial ligation of the left "lumbotesticular" trunk vein in rabbits. HBO was administered to one of the two groups of VC model rabbits after the operation. Weight and volume of both testes, parameters of seminal fluid, histological changes of testicular tissues, MTDs, TFI, and Sertoli cell index (SI) of seminiferous tubules were studied.</p><p><b>RESULTS</b>The average weight and volume of the left testes significantly increased in the rabbits treated by HBO. The semen quality was improved, and MTDs increased significantly compared with VC group(P < 0.0001). The testicular tissue morphology became nearly normal in VC + HBO group.</p><p><b>CONCLUSIONS</b>1. Both the structure and spermatogenetic function of testes can be damaged by the presence of varicocele; 2. Chronic ischemia, anoxia and microcircular dysfunction may be the key process and essential factor that make varicocele contributive to testicular damage and spermatogenetic dysfunction; 3. HBO can effectively alleviate, even eliminate, chronic ischemia, anoxia and microcircular dysfunction in testicular tissues with varicocele, and thus protect the structure and functions of testes.</p>

Early rehabilitation of acute stroke with acupuncture / 中国康复理论与实践

@#ObjectiveTo study the effct of the early rehabilitation of acute stroke with acupunction added to rehabilitational training.Methods120 patients with acute stroke were divided into 2 growps with 60 cases each:the acupunction growp,in which the patients were acepted acupuncture added to rehabilitational training,and the control growp,in which the patients were acepted the rehabilitational training only.All the patients were evaluated with Clinical Nervous Functional Deficiency(CNFD),Fugl-Meyer Assessment(FMA) and Modified Barthel Index(MBI).Results The scales of CNFD,FMAanal Deficiency (CNFD),Fugl-Meyer Assess me that of the control growp.The rate of cure and significantly in the acupunction growp was 75%,while that of the control growp was 41.7%(P<0.01).Conclusions Acupunction compared with the rehabilitational training is effective on the with stroke.