水溶性分药法对心脏机械瓣膜置换术后患者服用华法林抗凝效果的影响

目的:比较心脏机械瓣膜置换术后患者服用华法林时两种分药方法抗凝有效性及安全性。方法:把107例心脏机械瓣膜置换术后口服华法林的患者随机分观察组(52例)和对照组(55例),观察组用水溶法,对照组用干分法,比较两组患者用药剂量的准确性及抗凝效果。结果:两组患者服药前、服药后1d、服药后3d血浆凝血酶原时间(PT)、国际标准化比值(INR),差异无统计学意义(P>0.05),服药后5d、1周、3周、1月、2月、3月、6月PT和INR比较,对照组PT值和INR变化大,差异有统计学意义(P<0.05);而观察组首次达目标(INR)范围的时间后变异小,差异无统计学意义(P>0.05)。对照组患者INR<1.6,INR>3.0的比例及出血、栓塞发生率高于观察组患者,差异有统计学意义(P<0.05)。结论:心脏瓣膜置换术后应用华法林抗凝时,水溶法分剂量更准确,安全性更高。

Enantioselective analytical methods in chiral drug metabolism

The chiral nature of biological systems enables their stereoselective interaction with chiral compounds. It has been well documented that the enantiomers ofa chiral drug may show differences in drug disposition especially in metabolic behavior. As a result, it is of vital importance to separate the enantiomers of a chiral drug in metabolic studies. This paper discusses enantioselective methods （include high-performance liquid chromatography, gas chromatography, capillary electrophoresis and high-performance liquid chromatography-mass spectrometry） that applied in chiral drug metabolism, using most recent examples where possible.

Chemical Constituents of Angelica sinensis

Aim To investigate the active constituents responsible for thepharmacological activities of Angelica sinensis (Oliv) Diels. Methods Chromatography was used toisolate chemical components, and spectroscopy was used to identify their structures. Results Sevencompounds were isolated and their structures were identified as ferulic acid (1), conife-rylferukte(2) , bis (2-ethylhexyl) phthalate (3), dibutyl phthalate (4), lignoceric acid (5), palmitic acid(6), and Z-6, 7-cis-dihydroxyligustilide (7) Conclusion Bis (2-ethylhexyl) phthalate and dibutylphthalate were obtained from Angelica sinensis for the first time.

Qualitative and Quantitative Analysis of Rhizoma of Polygonum cuspidatum

Aim To establish reliable methods for evaluating the quality of rhizoma of Polygonum cuspidatum( Huzhang in Chinese). Methods TLC and HPLC were employed for the chemical identification and content determination,respectively. Results A qualitative TLC method and a quantitative HPLC method with piceid as the reference substance were established, respectively. With piceid as the reference substance and ethyl acetate-methanol-formic acid-water ( 19:3:0.5:1) as the mobile phase, a TLC method for the identification of Huzhang from the commonly used crude drugs of the same family was also set up. Conclusion The established TLC method can reasonably appraise the quality of the drug and easily distinguish Huzhang from the other commonly used crude drugs of the same family. The HPLC method for determining piceid is simple, reproducible, accurate, and feasible.

Spectrophotometric Determination of Chlordiazepoxide Using Its Charge-transfer Complex with 2,4-Dinitrophenol

A new simple, rapid and sensitive spectrophotometric method for the determination of chlordiazepoxide is described, based on the reaction with 2,4-dinitrophenol in water medium, apparently by a charge-transfer mechanism, to yield 1:1 complex with maximum absorption at 444 nm. Optimum experimental conditions for the determination have been studied. The linear calibration range, apparent molar absorptivity and relative standard deviation are 2.8~96.0 mgmL-1, 1.48103 and 0.32%, respectively. The method is accurate and has been successfully applied to the determination of chlordiazpoxide in tablets. The results are in good agreement with those obtained with the official method.

Influence of maximum decking charge on intensity of blasting vibration

Based on the character of short-time non-stationary random signal, the relationship between the maximum decking charge and energy distribution of blasting vibration signals was investigated by means of the wavelet packet method. Firstly, the characteristics of wavelet transform and wavelet packet analysis were described. Secondly, the blasting vibration signals were analyzed by wavelet packet based on software MATLAB, and the change of energy distribution curve at different frequency bands were obtained. Finally, the law of energy distribution of blasting vibration signals changing with the maximum decking charge was analyzed. The results show that with the increase of decking charge, the ratio of the energy of high frequency to total energy decreases, the dominant frequency hands of blasting vibration signals tend towards low frequency and hlasting vibration does not depend on the maximum decking charge.

Allosteric modulation of cholinergic system:Potential approach to treating cognitive deficits of schizophrenia

Schizophrenia is a psychiatric disorder affecting approximately 1% of the population worldwide and is characterised by the presence of positive and negative symptoms and cognitive deficits. Whilst current therapeutics ameliorate positive symptoms, they are largely ineffective in improving negative symptoms and cognitive deficits. The cholinergic neurotransmitter system heavily influences cognitive function and there is evidence that implicates disruption of the central cholinergic system in schizophrenia. Historically, targeting the cholinergic system has been impeded by poor selectivity leading to intolerable side effects warranting the need to develop more targeted therapeutic compounds. In this review we will summarise evidence supporting the roles of the cholinergic system, particularly the muscarinic M1 receptor, in the pathophysiology of schizophrenia and discuss the potential of a promising new class of candidate compounds, allosteric ligands, for addressing the difficulties involved in targeting this system. The body of evidence presented here highlights the dysfunction of the cholinergic system in schizophrenia and that targeting this system by taking advantage of allosteric ligands is having clinically meaningful effect on cognitive deficits.

Professor Ouyang Heng's Experience in Treating Neurodermatitis

Neurodermatitis, also called chronic simple lichen,is a common chronic inflammatory dennatosis characterized by paroxysmal severe itching and cutaneous lichenification. In clinic, this disease is often seen with the symptoms caused by dampness,heat and blood stasis.

Emerging pharmacological strategies for the treatment of fibromyalgia

Fibromyalgia(FM) has been described as a chronic clinical condition related to multisensory hypersensitivitypresenting with a complex of symptoms dominated by chronic widespread pain associated with the existence of a range of co-morbidities, such as fatigue, sleep disturbance, cognitive impairment, anxiety and depression. Current treatments include drugs that target serotonin and noradrenaline levels within the central nervous system, e.g., tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, and voltage-gated calcium channel subunit ligands, e.g., gabapentin and pregabalin. Investigation of a range of novel targets, such as melatoninergic, cannabinoid, dopamine, NMDA, angiotensin, orexin and opioid receptors, and ion channels, in addition revisiting bioamine modulation and subunits has provided efficacy outcomes that improve the health status of patients with FM. Nevertheless, modest and limited efficacy is often observed reflecting the heterogeneity of FM with existence of subpopulations of patients, the contribution of peripheral and central components to the pathophysiology, and the extensive range of accompanying co-morbidities. The complexity and multidimensional nature of FM is emphasized by the diversity of pharmacological targets gaining interest. Clues to underlying mechanisms which offer themselves as novel and potential targets for new medications are being provided by advances in the understanding of the pathophysiology of FM.

Recent advances in cellular and molecular aspects of mammalian retinal ischemia

Retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Generally, ischemic syndromes are initially characterized by low homeostatic responses which, with time, induce injury to the tissue due to cell loss by apoptosis. In this re-spect, retinal ischemia is a primary cause of neuronal death. It can be considered as a sort of fnal common pathway in retinal diseases and results in irreversible morphological and functional changes. This review summarizes the recent knowledge on the effects of ischemia in retinal tissue and points out experimental strategies/models performed to gain better compre-hension of retinal ischemia diseases. In particular, the nature of the mechanisms leading to neuronal damage （i.e., excess of glutamate release, oxidative stress and infammation） will be outlined as well as the potential and most intriguing retinoprotective approaches and the possible therapeutic use of naturally occurring molecules such as neuropeptides. There is a general agreement that a better understanding of the funda-mental pathophysiology of retinal ischemia will lead tobetter management and improved clinical outcome. In this respect, to contrast this pathological state, spe-cifc pharmacological strategies need to be developed aimed at the many putative cascades generated during ischemia.

A Monoterpene Glycoside from Ehinacea purpurea

Aim To separate and identify chemical constituents of Ehinacea purpurea . Methods Five compounds were isolated from the plant using chromatography. Their structures were elucidated by spectroscopy. Results Five compounds were isolated and their structures were identified as 2, 6 dimethyl 7 octene 2, 3, 6 triol 2 O β D glucopyranoside (1), 7, 8 furocoumarin (2), 6 methoxy 7 hydroxycoumarin (3), caffeic acid (4), methyl caffeate (5), and ethyl caffeate (6). Conclusion All these compounds were obtained from the plant for the first time.

Study on alantolactone-induced differentiation of mesenchymal stem cells intovascular cells

To promote efficient screening of active angiogenic drugs from traditional medicines, we constructed a humanembryonic kidney-293 cell model using vascular endothelial growth factor （VEGF） gene promoter as the drug target. Inthis model, VEGF gene promoter may regulate the expression of the luciferase reporter gene by responding to thestimulation of drug molecules. This cell model allows rapid and efficient screening of vascular-inducing activecomponents from several drug monomer molecules. Furthermore, we used rat bone marrow mesenchymal stem cells（rMSCs） to conduct a preliminary study on the activity of alantolactone. Using simvastatin as a positive control, weinvestigated the effects of alantolactone on the expression of vascular-related cell marker molecules such as VEGF andα-smooth muscle actin （α-SMA） in rMSCs. According to our results, 0.1, 1, 3 and 5 μM of alantolactone upregulated thetranscriptional luciferase gene activity of VEGF promoter, and a significant difference from that in the control group wasobserved. Among them, 3μM of alantolactone showed the better effect than that of 3 μM of simvastatin （P = 0.036） andother concentrations of alantolactone and simvastatin showed similar effects. Compared with that in the control group,rMSCs induced with 1μM alantolactone for 3 days showed a significant increase in the relative mRNA expressions ofVEGF and α-SMA genes. However, these effect of 5 μM alantolactone were weaker than those of 5 μM simvastatin （P 〈0.05）; rMSCs treated with 1 μM alantolactone for 3 days showed brighter green fluorescence （FITC marker） of α-SMAand VEGF in situ expression than that observed in the control group and similar fluorescence intensity than that ofsimvastatin group in an immunoradiometric assay. The above results demonstrate the reliability of the highly efficientsystem for screening of active drug molecules and confirmed the vascular induction function of alantolactone at the geneand protein levels.

Prevention and Treatment of KSHV-associated Diseases with Antiviral Drugs

Kaposi’s sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi’s sarcoma (KS) in 1994. KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD). Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons. The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.

Telomerase activity: An attractive target for cancer therapeutics

Telomeres are non-coding tandem repeats of 1000-2000 TTAGGG nucleotide DNA sequences on the 3’ termini of human chromosomes where they serve as protective “caps” from degradation and loss of genes. The “cap” at the end of chromosome required to protect its integ-rity is a 150-200 nucleotide-long single stranded G-rich 3’ overhang that forms two higher order structures, a T-loop with Sheltering complex, or a G-quadruplex com-plex. Telomerase is a human ribonucleoprotein reverse transcriptase that continually added single stranded TTAGGG DNA sequences onto the single strand 3’ of telomere in the 5’ to 3’ direction. Telomerase activity is detected in male germ line cells, proliferative cells of renewal tissues, some adult pluripotent stem cells, embryonic cells, but in most somatic cells is not de-tected. Re-expression or up-regulation of telomerase in tumours cells is considered as a critical step in cell tumorigenesis and telomerase is widely considered as a tumour marker and a target for anticancer drugs. Dif-ferent approaches have been used in anticancer thera-peutics targeting telomerase. Telomerase inhibitors can block directly Human TElomerase Reverse Transcrip-tase （hTERT） or Human TElomerase RNA telomerase subunits activity, or G-quadruplex and Sheltering complex components, shortening telomeres and inhibiting cell proliferation. Telomerase can become an immune target and GV1001, Vx-001, I540 are the most wide-spread vaccines used with encouraging results. Another method is to use hTERT promoter to drive suicide gene expression or to control a lytic virus replication. Recently telomerase activity was used to activate pro-drugs such as Acycloguanosyl 5’-thymidyltriphosphate, a synthetic ACV-derived molecule when it is activated by telomer-ase it does not require any virus or host active immune response to induce suicide gene therapy. Advantage of all these therapies is that target only neoplastic cells without any effects in normal cells, avoiding toxicity and adverse effects of the current chemotherapy. However, as not all the approaches are equally effcient, further studies will be necessary.

Models for depression in drug screening and preclinical studies:Future directions

The basic consideration in the feld of antidepressants is that tests to model depression do not exist, as de-pression etiopathology is unknown. So far, any kind of proposed model for depression needs to satisfy construct, face and predictive validities. In the present editorial, this idea is challenged, based on the fact that “old” methods can only reveal therapeutical “me-too” drugs and that there is no longer a need of therapeu-tical “me-too” drugs in the field of antidepressants. Since reduction in the number of antidepressant non-responders is a real medical need, the predictive valid-ity of animal models will be challenged in the future, as the new methods should be based on antidepressant-insensitive animals. Moreover, antidepressants exert similar effects in depressed and non-depressed sub-jects, but mood normalization is only induced in de-pressed patients. This implies that the use of normal cells and animals only involves pharmacological rather than therapeutical actions of drugs. Therefore, the use of environmental-induced changes, in the hope that these can evidence antidepressant-insensitive animals, will predominantly be used in the future. In the choice of experimental settings, other factors need to be taken into consideration： （1） gender of animals, as de-pression affects females more than males, （2） natural rhythmicity in drug effects; （3） pharmacokinetics; and （4） possible biomarker（s） to be measured. There are no golden recipes to discover new antidepressants but the experimental long-term strategy should very clearly be declared before starting the experiments.

Determination of anthraquinone prodrug and its hydrolytically active compounds using RP-HPLC

In order to study the hydrolytic characterization of an anti-inflammatory prodrug （ RI-1 ） in vitro, an effective, accurate and reliable method for the simultaneous determination of the prodrug and its two hydrolytic active compounds is developed using reverse phase high-performance liquid chromatography （RP-HPLC）. The chromatographic separation is performed on an ODS-2 C18 column （250 mm × 4. 6 mm, 5.0 μm particle size） with a simple elution program. The mobile phase is V（ methanol） ： V（0. 1% phosphoric acid solution） =90：10 （adjust pH to 2. 3）. A wavelength of 225 nm and a mobile phase flow rate of 1.0 mL/min are utilized for the quantitative analysis. Excellent linear behaviors over the investigated concentration ranges are observed with values of R2 higher than 0. 999 for all the analytes. The validated method is successfully applied to the simultaneous determination of the prodrug and its active components can be used to detect hydrolytic characterization in vitro.

Thoughts About Paths for Digitization of Traditional Chinese Medicine-Refined Data Elements

For digitalization of traditional Chinese medicine(TCM),research is being conducted on objectivization of diagnosis and treatment,mathematical models of TCM theories,and application of modern information technology to digitize the vast amounts of existing information.However,the author believes that TCM practitioners should first conduct a systematic and comprehensive refined analysis on the knowledge of TCM and unify data elements used in computer intelligence to avoid ambiguity.Thus,we must overcome the epistemological constraints and carefully analyze the relationship among data elements to achieve systematic results and administer TCM appropriately.

Therapeutic effect of different treatment methods on functional anorectal pain

Objective： To observe the clinical efficacy of oral traditional Chinese medicine （Jiaweitiaoqi decoction）, electroacupuncture, biofeedback, and combined treatment on functional anorectal pain （FAP）. Methods： A total of 200 patients with FAP were randomly divided into 4 groups, with 50 patients in each group. Group 1 was given oral Jiaweitiaoqi decoction; group 2 was given electroacupuncture at the lumbosacral acupoints; group 3 was given biofeedback training; and group 4 was given combined treatment. The numeric rating scale （NRS）, Short Form-36 （SF-36） quality of life scale, static pressure of the anal canal, and maximum systolic pressure were observed in the 4 groups. Results： The observation indices of the 4 groups were all improved after treatment compared with those before treatment, and the fourth group showed the most obvious improvement. Regarding NRS scores, the static pressure of the anal canal, and maximum systolic pressure, group 4 had lower values than the other 3 groups （P 〈 0.05 for all）. In the SF-36 quality of life score, group 4 showed a higher value than the other 3 groups （P 〈 0.05）. Conclusion： Non-drug therapy including acupuncture and physical exercise can enhance the clinical efficacy of single Chinese medicine in the treatment of FAP .

TCM Treatment of Parkinson's Syndrome—A Report of 40 Cases

In recent years, we have treated 40 cases of Parkinson's syndrome with the principles of reinforcing and supplementing the liver- and kidneyyin, calming endogenous wind and removing the obstruction from the channels. The results were satisfactory and reported as follows.

Mirabegron, a novel, non-antimuscarinic drug for the overactive bladder: An up-to-dated review

Mirabegron opened a new era in the treatment of overactive bladder(OAB). For the fi rst time physicians dealing with OAB have an effective alternative to the pharmacological mainstay of the therapy for this disorder, the antimuscarinic drugs. This fi rst-in-class, potent β3-adrenoceptors agonist has recently received approval by regulatory authorities in Japan, United States and Europe, based on the favourable efficacy-tolerability profile demonstrated in multiple randomized, multinational, controlled trials, both short and long-term. There is substantial consistency through the studies in reporting the cardiovascular safety of treatment with mirabegron. The main advantage of mirabegron is the placebo-like incidence of classic adverse effects caused by antimuscarinics, dry mouth and constipation, that is expected to improve long-term adherence of patients to treatment. Mirabegron can be used in patients with contraindications to antimuscarinics and in those who discontinued previous antimuscarinic therapy. Herein, we reviewed the published literature on mirabegron, focusing on the rationale of β3-agonism for OAB treatment and on the preclinical and clinical evidence of effi cacy and safety available on this new pharmacological principle.