Studies on the prescription combination regularity based on medicinal tastes focus on the internal relations between the structure and hierarchy of the prescription combination system. In this paper, with the systematic and scientific self-similarity theory as the core ideology, authors systematically interpreted the self-similarity theory of medicinal properties, defined the self-similarity of prescriptions with identical or similar medicinal properties, and built the systematic view of medicinal property theory based on the prescription combination based on the entity grammar system. As a result, the system was conducive to integrating traditional Chinese medicinal knowledge of syndromes, therapeutic principles, efficacies, medicinal properties and tastes and achieving the automatic design and optimization process from symptoms to prescriptions, and providing scientific and feasible methods and technical systems for the application of the medicinal property theory, with a guiding significance to the technology, methodology and theory of decoction pieces compatibility, component compatibility and compound medicine design.
Drug Combinations ; Drug Prescriptions ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional

Objective To investigate the role of connexin 43(Cx43)in the apoptosis of pancreatic cancer cell line BxPC and its possible mechanism.Methods pcDNA-Cx43,pcDNA-Cx43N,pcDNA3.0,siRNA-Cx43 and siRNA-NC were transfected into BxPC3 cells via liposome method.Cx43 protein and Cytochrome C(Cyt C)concentration was determined by Western blot,and the apoptosis was analyzed by Annexin V/PI binding assay.The mitechondria apoptosis pathway involved in Cx43 associated apoptosis was examined which contains the depolarization of mitechondrial membrane potential (MMP);fluorospectrophotometer was used to measure the activities of caspase-3 and caspase-9. Gap junction intercellular communication(GJIC) was determined by dye-transfer method.Results Cx43 protein expression increased after BxPC3 transfeetion,apoptosis rate increased from(6.35±0.43)%in empty vector transfection group to(14.29±1.24)%;after H202 treatment,apoptosis rate increased from(20.34±2.47)%to(31.27±2.56)%(P<0.05).Meanwhile,mitochondrial membrane potential was decreased,Cyt C was increasingly released from mitochondria,caspases activities were increased;after siRNA43 interference,apoptosis rate decreased from(7.42±0.47)% to(5.19±1.37)%,after H_2O_2 treatment,apoptosis rate decreased from (19.43±1.71)%to(11.67±1.97)%(P<0.05).Decreased mitochondrial membrane potential and Cyt C release were observed,caspases activities were decreased.GJIC of pcDNA-Cx 43 transfection group increased from 14.52±0.57 to 23.05±3.84.and it increased from 1.70 ±0.24 to 3.84 ±0.45 in the presence of β-GA(P<0.05).But the apoptosis rate was not significantly different.Conclusions Cx43 could promote BxPC3 apoptosis via mitochondrial apoptotic signal pathway,and the possible mechanism included signal pathway other than GJIC.

AIM:To explore whether histamine can regulate the expression of early growth response factor-1 (Egr-1) in the cerebral cortex astrocytes.METHODS:Normal wild-type (WT) mice, histidine decarboxylase knockout ( HDC-KO) mice and histamine treated HDC-KO mice were sacrificed for extracting the total RNA of the cerebral cortex. Primary cultured rat cortical astrocytes were treated with histamine at concentrations of 10 -8 , 10 -7 , 10 -6 , 10 -5 or 10 -4 mol/L for 15, 30, 60, 120 or 240 min.H1 or H2 receptor antagonists were pretreated for 15 min before histamine treat-ment.After histamine treatment, the cell total RNA or protein was extracted.The expression of Egr-1 at mRNA and protein levels was determined by real-time PCR and Western blot.RESULTS:The mRNA level of Egr-1 in cerebral cortex of HDC-KO mice was significantly lower than that in WT mice, while exogenous histamine induced the mRNA expression of Egr-1 in HDC-KO mice.In cultured astrocytes, histamine induced the mRNA expression of Egr-1.The maximum increase in the mRNA level of Egr-1 was produced by histamine at concentration of 10 -5 mol/L.In addition, histamine-induced Egr-1 mRNA accumulation peaked at 30 min after commencing stimulation, while histamine significantly increased Egr-1 protein expression at 60 min.Furthermore, histamine-induced Egr-1 expression was inhibited by H1 receptor antagonist but not H2 receptor antagonist.CONCLUSION:Histamine up-regulates the Egr-1 expression in cerebral cortex and cultured astrocytes, which may attribute to H1 receptor activation.

Objective:To analyze the relationship of lipoprotein associated phospholipase A 2 (Lp-PLA2) and severity of coronary atherosclerosis, and evaluate the effects of rosuvastatin at different doses on the concentration of plasma Lp -PLA2.Methods: Totally 152 cases of patients with suspected coronary heart disease were treated with coronary angiography .According to the results of angiogra-phy, the patients were divided into the coronary heart disease group ( n=117 ) and the normal control group ( without coronary heart disease,n=35).Gensini integral scale was performed and referring to the number of diseased coronary arteries , the degree of coronary atherosclerosis was evaluated .The concentration of serum Lp-PLA2 was detected and the relationship of Lp-PLA2 and the severity of coronary plaque was evaluated .Meanwhile , the patients with coronary heart disease were divided into 2 groups and orally treated with rosuvastatin respectively at the routine dose (10 mg· d-1 ) and the loading dose (20 mg· d-1 ).The changes of the plasma concentra-tion of Lp-PLA2 before the treatment, in the 2nd, 4th,8th and 12th week after the medication were measured and the effect of atorvastatin at different doses on the plasma concentration of Lp-PLA2 was summarized .Results: The plasma Lp-PLA level in the control group was (22.22 ±1.75) μmol· ml-1, while that in the coronary heart disease group was (29.03 ±3.99) μmol· ml-1(P<0.05).The differences in Lp-PLA2 levels between the groups with different Gensini scores of coronary heart disease were statistically significant ( P<0.05).The higher scores were, the higher Lp-PLA2 levels were.The results of multivariate analysis showed that the severity of cor-onary atherosclerosis was significant and positive correlated with Lp-PLA2 level (OR=1.613,P<0.05).In the 2nd, 4th, 8th and 12th week after the medication , Lp-PLA2 levels in the loading dose group were significantly lower than those in the routine dose group ( P<0.05).In the 2nd, 4th, 8th and 12th week after the medication, the degree scores of coronary artery stenosis in the loading dose group were reduced.The decreasing range was significantly greater than that in the routine dose group (P<0.05).The incidence of adverse cardiovascular events in the routine dose group (27.12%) was significantly higher than that in the loading dose group (6.90%) ( P<0.05).The incidence of adverse drug reactions in the routine dose group was 11.86%, while that in the loading dose group was 18.97%(P>0.05).Conclusion:Lp-PLA2 is correlated with the severity of coronary plaque .High dose of rosuvastatin can reduce plasma Lp-PLA2 concentration in the patients .

Objective To study the clinical characteristics and outcome of cytomegalovirus(CMV) infection in infants.Methods All data including time of infection,clinical characteristics,laboratory tests and outcome of CMV infections in hospitalized infants were collec-(ted) and analyzed from January,1994 to July,2004.Results In 87 infected infants,congenitally infected newborns,perinatal infection in infants and postnatal infection in infants accounted for 27.6%,62.0%,16.6%,respectively.CMV hepatitis was the most frequent type of disease with the incidence of 41.3%,in which the incidence of splenomegaly was 10.3%.Most of CMV hepatitis infants had a good prognosis with the improved rate 80.5%.Central nervous system abnormality(including abnormal intension of muscle,convulsion,ocular and hearing abnormalities) occurred only in congenital and perinatal infection with the incidence of 20.4%.Generalized infection,the incidence of congenital infection and perinatal infection was 16.7%,1.8%,respectively.It did not occur in postnatal infection.The mortality rate of congenital infection and perinatal infection were 12.5% and 1.85%,respectively.Conclusions CMV infection is the main cause of infant hepatitis and it can also cause neurologic sequelae.The outcome of generalized infection in congenital infection is bad and the mortality rate is high.

The on-line monitor for the changes in the content of baicalin in Scutellariae Radix formula particles during the extraction process was conducted by using near infrared spectroscopy (NIR). High performance liquid chromatography (HPLC) was used as a reference method. Kennard-Stone (KS) was used to divide sample sets, so as to compare different pretreatment methods. The synergy interval partial least squares (SiPLS) was used to screen out modeling wave band to establish partial least-squares models. The relative error method was applied to predict forecast set samples of Scutellariae Radix in three extraction phases. The results showed that the model established by Savitzky-Golay smoothing with 11 points (SG11 points) was the best, with the root mean square with cross validation (RMSECV), root mean square error of correction (RMSEC) and root mean square error of prediction (RMSEP) of baicalin of 0.092 7, 0.134 4 and 0.114 8, respectively, the determination coefficient R2 of greater than 0.99, and the relative error of baicalin content of less than 5%. This indicates that the on-line near infrared reflectance spectroscopy could be applied in on-line monitor and quality control of the extraction process of Scutellariae Radix formula particles.
Automation ; methods ; Drugs, Chinese Herbal ; chemistry ; standards ; Quality Control ; Scutellaria baicalensis ; chemistry ; Spectroscopy, Near-Infrared ; methods

In this paper, the process performance indexes (PPIs) P(p) and P(pk) were introduced and applied to evaluate the process capability and quality consistence of Chinese medicine products. The historical quality analysis data of Qingkailing injection were collected and taken as the research object. The confidence intervals of P(p) and P(pk) were estimated based on the Bootstrap sampling methods. Results showed that the value and width of the confidence interval P(p) of were smaller that of P(pk) suggesting that the P(pk) index was more sensitive than P(p) in process capability analysis. Within the production period concerned, the P(pk) values estimated from different quality indexes of Qingkailing injection, such as baicalin, cholic acid, geniposide and total nitrogen, were 1.122, 2.055, 1.564 and 0.891, respectively. It could be found that the cholic acid had the highest process capability, followed by the geniposide and baicalin. The total nitrogen had the lowest process capability, indicating that it is necessary to reinforce the quality management of total nitrogen related manufacturing processes. The case studies demonstrate the effectiveness and feasibility of PPIs, which are convenient to be used in production practice of Chinese medicine.
Chemistry, Pharmaceutical ; methods ; standards ; Drugs, Chinese Herbal ; chemistry ; standards ; Injections ; Quality Control

OBJECTIVEThe efficiency network is a complicated network for revealing the efficient mechanism of traditional Chinese medicines (TCMs) and relations among efficiencies. The efficiency-property relations were used to establish a warm-pungent-liver efficiency network to explain the principle of treating hepatoma with medicines invigorating blood circulation and eliminating blood stasis. Safflower, a warm-pungent medicine distributing along the live meridian, was taken for example to discuss the efficiency network' s application in the identification of active ingredients of TCMs and the combination.

METHODIn the early stage of this study, combined warm-pungent-liver medicines distributed along the liver meridian and invigorating blood circulation and eliminating blood stasis were taken as the study objects to collect the pharmacological effect data of warm-pungent-liver medicines and obtain the pharmacological effect combinations with the highest blood circulation-invigorating association by the association rules and the chi-square test. The pharmacological target data recorded in the DrugBank database is used to establish the warm-pungent-liver efficiency network according to the principle line of "efficiency-property-pharmacology-target-protein interaction" under the background of the protein interaction network.

RESULTThe blood circulation-invigorating medicines could directly treat hepatoma by impacting protooncogene, cancer suppressor gene, cell apoptosis and anti-inflammation, and indirectly treat hepatoma by resisting coagulation and adhesion, regulating local blood circulation, preventing cancer cell metastasis and enhancing the tissues' sensitivity to the anticancer drugs. Among the active ingredients of safflower screened based on the blood circulation-invigorating network targets, carthamin yellow, quercetin and luteolin have been proved to have the anti-hepatoma effect in literatures, which indicated the reliability of this study's results and the purpose of the efficiency network.

CONCLUSIONThe efficiency network is an effective method for revealing the TCM's mechanism, and lays a foundation for discovering key active ingredients of TCMs for treating specific diseases.

Antineoplastic Agents, Phytogenic ; chemistry ; therapeutic use ; Blood Circulation ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; genetics ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Gene Regulatory Networks ; drug effects ; Humans ; Liver ; blood supply ; drug effects ; Liver Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology

The design space of the high shear wet granulation process was established and validated within the framework of quality by design (QbD). The system of microcrystalline cellulose-de-ioned water was used in this study. The median granule size and bulk density of granules were identified as critical quality attributes. Plackeet-Burmann experimental design was used to screen these factors as follows: dry mixing time, the impeller and chopper speed of dry mixing, water amount, water addition time, wet massing time, the impeller and chopper speed of wet massing and drying time. And the optimization was implemented with the central composite experimental design based on screened critical process parameters. The design space of the high shear wet granulation process was established based on the quadratic polynomial regression model. Since the P-values of both models were less than 0.05 and values of lack of fit were more than 0.1, the relationship between critical quality attributes and critical process parameters could be well described by the two models. The reliability of design space, illustrated by overlay plot, was improved with the addition of 95% confidence interval. For those granules whose process parameters were in the design space, the granule size could be controlled within 250 to 355 μm, and the bulk density could be controlled within a range of 0.4 to 0.6 g x cm(-3). The robustness and flexibility of the high shear wet granulation process have been enhanced via the establishment of the design space based on the QbD concept.
Cellulose ; chemistry ; Reproducibility of Results ; Technology, Pharmaceutical ; methods ; Water

Near-infrared (NIR) diffuse reflectance spectroscopy was used to analyze the impact of multi-class particle size of Chinese material medica (CMM) based on the spectral characteristics in overtone and combination region. Several types of CMM (60, 80, 100,120 mesh) were subjected to NIR spectra analysis. Spectral reproducibility was examined after sample repackage. The result showed that the effects of particle size on the NIR spectra were different according to different bands, in the combination region and first combination-overtone region. Spectroscopy intensity was proportional to the particle size and influence of particle size was greater as the wavelength increased. While in the second combination-overtone region, it was inversely proportional to particle size. To the sampling loading error, the result indicated that when the mesh number was larger than 60 mesh, the error was small. The appropriate particle size was clarified to guarantee the accuracy and reliability of NIR diffuse reflectance spectroscopy in CMM.
Drugs, Chinese Herbal ; analysis ; Materia Medica ; analysis ; Particle Size ; Spectroscopy, Near-Infrared ; methods