Discovery of an Orally Efficacious MYC Inhibitor for Liver Cancer Using a GNMT-Based High-Throughput Screening System and Structure-Activity Relationship Analysis.

Glycine-N-methyl transferase (GNMT) downregulation results in spontaneous hepatocellular carcinoma (HCC). Overexpression of GNMT inhibits the proliferation of liver cancer cell lines and prevents carcinogen-induced HCC, suggesting that GNMT induction is a potential approach for anti-HCC therapy. Herein, we used Huh7 GNMT promoter-driven screening to identify a GNMT inducer. Compound K78 was identified and validated for its induction of GNMT and inhibition of Huh7 cell growth. Subsequently, we employed structure-activity relationship analysis and found a potent GNMT inducer, K117. K117 inhibited Huh7 cell growth in vitro and xenograft in vivo. Oral administration of a dosage of K117 at 10 mpk (milligrams per kilogram) can inhibit Huh7 xenograft in a manner equivalent to the effect of sorafenib at a dosage of 25 mpk. A mechanistic study revealed that K117 is an MYC inhibitor. Ectopic expression of MYC using CMV promoter blocked K117-mediated MYC inhibition and GNMT induction. Overall, K117 is a potential lead compound for HCC- and MYC-dependent cancers.

Four new phenanthrene derivatives from Bulbophyllum retusiusculum.

Three new dihydrophenanthrenes, retusiusine D (1), retusiusine E (2), retusiusine F (3), and a new phenanthrene retusiusine G (4), together with two known dihydrophenanthrenes 4,7-dihydroxy-2,3-methylenedioxy-9,10-dihydrophenanthrene (5) and epemeranthol-A (6) were isolated from the tubers of Bulbophyllum retusiusculum. Their structures were established on the basis of extensive spectroscopic analyses. Compounds 1 and 2 exhibited potent cytotoxic activities against SMMC-7721 and weak cytotoxic activities against HL-60. Compound 4 showed moderate cytotoxic activity against SMMC-7721 and MCF-7.

Appropriate intraprocedural initial heparin dosing in patients undergoing catheter ablation for atrial fibrillation receiving uninterrupted non-vitamin-K antagonist oral anticoagulant treatment.

BACKGROUND: To clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment. METHODS: A total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250-350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed. RESULTS: There was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300-350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed. CONCLUSIONS: For patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier. TRIAL REGISTRATION: Registration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx ).

Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System.

OBJECTIVE: To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI). METHODS: Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg-1·d-1, respectively) groups, atorvastatin (ATV) group (7.2 g·kg-1·d-1), chloroquine (CQ) group (10 g·kg-1·d-1), and highdose TXL + CQ group. After pharmacological administration for 7 days, rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting. RESULTS: Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL. CONCLUSIONS: TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

Early Intervention of Tongxinluo () on Right Ventricular Function Assessed by Echocardiography in Rats with Pulmonary Arterial Hypertension Induced by Monocrotaline.

OBJECTIVE: To investigate the effect of early intervention of Tongxinluo (, TXL) on right ventricular function (RVF) of rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). METHODS: A total of 30 adult male Sprague-Dawley rats were assigned to 5 groups with complete random experiment design: Sham group (Sham), MCT group, TXL group, sildenafil (SIL) group and combination group (TXL+SIL), 6 rats in each group. Rats were injected with 50 mg/kg MCT solution for inducing PAH model except for those in the sham group. From the day of modeling, rats of TXL, SIL and TXL+SIL groups were given TXL (1.2 g/kg), SIL (10 mg/kg) and combination solution (TXL:1.2 g/kg, SIL: 10 mg/kg) respectively, and rats in Sham and MCT groups were given normal saline (5 mL/kg). The samples were collected and tested after 21 consecutive days of intragastric administration. Echocardiography was used to measure the related indices of RVF, including pulmonary arterial flow spectrum, pulmonary artery diameter (PAD), right ventricular wall thickness (RVWT), right ventricular diameter (RVD), tricuspidannular plane systolic excursion (TAPSE), right atrium transverse diameter (RAT), and inferior vena cava diameter (IVCD). Elastic Verhoeff-Van Gieson staining was adopted to measure the percentage of wall thickness (WT%) of pulmonary arteriols. Hematoxylin-eosin staining was used to measure the cross-sectional area (CSA) of right ventricular cardiomyocytes. RESULTS: MCT-induced PAH rat model was successfully established. In MCT group the wall of pulmonary arterioles exhibited a prominent-increase thickness, PAD, RVWT, RVD, RAT, IVCD, WT%, right ventricular hypertrophy index (RVHI) as well as CSA of RV cardiomyocyte significantly increased (all P<0.01), and TAPSE markedly decreased (P<0.01). At the same time, TXL prominently improved all of the above indices (all P<0.01). In comparison with SIL, TXL significantly reduced RVD (P<0.05) and decreased CAS of RV cardiomyocytes (P<0.01), but TAPSE in SIL group was much larger than in TXL group (P<0.01). Moreover, TAPSE in TXL+SIL group was larger than that in TXL group (P<0.01), while the two groups performed equally well in terms of the other indices. CONCLUSION: Early intervention of TXL could inhibit pulmonary arterioles remodeling, and improve RVF by attenuating right ventricular hypertrophy, and TXL has a stronger effect on inhibiting right ventricular remodeling than SIL.

Preventive effect of Tongxinluo on endothelial survival and vascular integrity, together with inhibition of inflammatory reaction in rats model of intestine ischemia/reperfusion injury.

This study was design to investigate preventive function of Tongxinluo (TXL) capsule on micro vascular function and endothelial survival in rats model of intestine ischemia/reperfusion (I/R) injury. We randomly divided fifty male Sprague-Dawley rats into Sham group, I/R group, TXL0.4+I/R group, TXL0.8+I/R group, TXL1.6+I/R group (10 rats each). Rat intestine I/R injury was carried out using a model of acute superior mesenteric artery occlusion with 30 min ischemia followed by 60 min reperfusion. The distribution of endothelial apoptosis in intestine was determined by CD31+TUNEL immunofluorescent double staining analysis. VE-Cadherin, ANGPTL4, HMGB1 and NF-κB were determined by immunohistochemical analysis. I/R induced massively endothelial cell apoptosis, accompanied with reduced expression of adherens junction protein VE-Cadherin and up regulation of inflammatory mediator HMGB1 and NF-κB. TXL pretreatment groups (TXL0.4+I/R, TXL0.8+I/R and TXL1.6+I/R group) significantly attenuated endothelial cell apoptosis with a dose-dependent effect. TXL pretreatment could maintain the expression of VE-Cadherin and promote the expression of ANGPTL4 which help to maintain endothelial integrity. TXL pretreatment also exert great influence in inhibiting HMGB1 expression and NF-κB expression induced by I/R. It could be concluded from this study that micro vascular dysfunction and endothelial damage play a causal role in rat intestine I/R injury. TXL pretreatment could significantly prevent the I/R induced pathology of endothelial apoptosis, micro vascular integrity disruption and inflammatory reaction.

New phenylpropanoids from Bulbophyllum retusiusculum.

Two new phenylpropanoids, retusiusines A (1) and B (2), and a pair of new phenylpropyl enantiomers, (±)-retusiusine C (3a and 3b), together with eight known compounds, dihydroconiferyl dihydro-p-coumarate (4), methyl 3-(4-hydroxyphenyl) propionate (5), 3-(4-hydroxyphenyl)-propanoic acid (6), dihydroferulic acid (7), methyl 3-(4-methoxyphenyl) propionate (8), 3-(3,4-dimethoxyphenyl)-2-propenal (9), trans-p-coumaric acid (10) and dihydroconiferyl alcohol (11), were isolated from the tubers of Bulbophyllum retusiusculum. The absolute configurations of the new compounds were determined by calculating their electronic circular dichroism (ECD), spectra and specific optical rotations and comparing the calculated values with the experimental data. Compound 2 exhibited potent antifungal activity against Candida albicans (16 µg/mL). Compound 3 showed moderate antibacterial activity against Bacillus subtilis (64 µg/mL).

HEMORHEOLOGY INDEX CHANGES IN A RAT ACUTE BLOOD STASIS MODEL: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Blood stasis has received increasing attention in research related to traditional Chinese medicine (TCM) and integrative Chinese and Western medicine. More than 90% of research studies use hemorheology indexes to evaluate the establishment of animal blood stasis models rather than pathological methods, as hemorheology index evaluations of blood stasis were short of the consolidated standard. The aim of this study was to evaluate the accuracy of hemorheology indexes in rat models of acute blood stasis (ABS) based on studies in which the ABS model had been confirmed by pathological methods. MATERIALS AND METHODS: We searched the Chinese National Knowledge Infrastructure database (CNKI), Chinese Medical Journal Database (CMJD), Chinese Biology Medicine disc (CBM), Wanfang database, and PubMed for studies of rat blood stasis models; the search identified 18 studies of rat ABS models induced by subcutaneous injection of epinephrine combined with an ice bath. Each included study received a modified Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) score list and methodological quality assessment, then data related to whole blood viscosity, plasma viscosity, platelet aggregation rate, erythrocyte aggregation index, and fibrinogen concentration were extracted. Extracted data were analyzed using Revman 5.3; heterogeneity was tested using Egger's test. RESULTS: A total of 343 studies of rat blood stasis were reviewed. Eighteen studies were included in this meta-analysis; the mean CAMARADES score was 3.5. The rat ABS model revealed a significant increase in whole blood viscosity (medium shear rate), whole blood viscosity (high shear rate), plasma viscosity, platelet aggregation rate, erythrocyte aggregation index, and fibrinogen concentration compared to controls, with weighted mean differences (WMD) of 2.42 mPa/s (95% confidence interval (CI) = 1.73 - 3.10); 1.76 mPa/s (95% CI = 1.28 - 2.24); 0.39 mPa/s (95% CI = 0.24 - 0.55); 13.66% (95% CI = 9.78 - 17.55); 0.84 (95% CI = 0.53 - 1.16); and 1.22 g/L (95% CI = 0.76 - 1.67), respectively. Subgroup analysis showed that whole blood viscosity, plasma viscosity, and the platelet aggregation rate test methods were more sensitive when measured at 0-24 h than at 24-72 h after induction of blood stasis. CONCLUSIONS: Rat blood stasis studies have incomplete experimental design and quality controls, and thus need an integrated improvement. Meta-analysis of included studies indicated that the unified hemorheology index of whole blood viscosity (medium and high shear rate), platelet aggregation rate, erythrocyte aggregation rate, and fibrinogen concentration might be used for assessment of rat ABS models independent of pathology methods.

Preparation and Characterization of Hyaluronic Acid-Polycaprolactone Copolymer Micelles for the Drug Delivery of Radioactive Iodine-131 Labeled Lipiodol.

Micelles, with the structure of amphiphilic molecules including a hydrophilic head and a hydrophobic tail, are recently developed as nanocarriers for the delivery of drugs with poor solubility. In addition, micelles have shown many advantages, such as enhanced permeation and retention (EPR) effects, prolonged circulation times, and increased endocytosis through surface modification. In this study, we measured the critical micelle concentrations, diameters, stability, and cytotoxicity and the cell uptake of micelles against hepatic cells with two kinds of hydrophilic materials: PEG-PCL and HA-g-PCL. We used 131I as a radioactive tracer to evaluate the stability, drug delivery, and cell uptake activity of the micelles. The results showed that HA-g-PCL micelles exhibited higher drug encapsulation efficiency and stability in aqueous solutions. In addition, the 131I-lipiodol loaded HA-g-PCL micelles had better affinity and higher cytotoxicity compared to HepG2 cells.

Anti-fibrotic effects of Salvia miltiorrhiza and Ligustrazine Injection on LX-2 cells involved with increased N-myc downstream-regulated gene 2 expression.

OBJECTIVE: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection (SML) on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2 (NDRG2, a tumor suppressor gene). METHODS: HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×104 cells/mL and cultured for 24 h followed by the application of different concentrations of SML (1, 2, 4 and 8 µL/mL). Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and ß-catenin were measured by Western blot. RESULTS: With the exception of the 1 and 2 µL/mL concentrations, 4 and 8 µL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h (P<0.05). With the exception of the 1 and 2 µL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of ß-catenin was unaffected. CONCLUSION: SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.

A new flavone C-glycoside and a new bibenzyl from Bulbophyllum retusiusculum.

A new flavone C-glycoside, apigenin 6-C-α-arabinofuranosyl 8-C-α-arabinopyranoside (1) and a new bibenzyl, bulbotetusine (2), were isolated from the tubers of Bulbophyllum retusiusculum. Their structures were established on the basis of extensive spectroscopic analyses. The absolute configuration of 2 was determined by the comparison of experimental and calculated electronic circular dichroism. Compounds 1 and 2 showed no obvious cytotoxic activity against any five human tumour cell lines with IC50 values >40 µM.

Salvia miltiorrhiza injection restores apoptosis of fibroblast-like synoviocytes cultured with serum from patients with rheumatoid arthritis.

Salvia miltiorrhiza injection (SMI) is a water­soluble agent, derived from Salvia miltiorrhiza (SM), that is traditionally used to treat cardiovascular and cerebrovascular diseases. Furthermore it has been demonstrated to possess the ability to induce apoptosis of tumor cells. However, it remains unclear whether SMI can induce apoptosis of rheumatoid arthritis (RA) fibroblast­like synoviocytes (FLS), which are hyperplastic in RA due to defective apoptosis. There is also evidence that allogenic serum may be associated with the induction of apoptosis. The aim of the present study was to investigate the involvement of serum during SMI­induced apoptosis in RA FLS. The results demonstrated that SMI could induce apoptosis of RA FLS, cultured with fetal bovine serum (FBS), in a dose­dependent manner. In addition, SMI decreased the expression of nuclear factor­κB in RA FLS nuclear extracts and inhibited the secretion of tumor necrosis factor­α. Fas ligand expression was not detected in RA FLS, in either the presence or absence of SMI. The pro­apoptotic genes B­cell lymphoma 2 (Bcl­2) associated X protein (Bax) and Fas, were shown to be upregulated following SMI stimulation, whereas the expression levels of the anti­apoptotic gene Bcl­2, were downregulated. Upon replacement of FBS with normal human serum, the apoptotic rate and Bax mRNA expression levels following SMI stimulation, were unchanged. However, culturing RA FLS with patient' serum (RPS), restored the apoptotic rate and Bax mRNA expression levels following SMI stimulation. There may be numerous mechanisms by which SMI inhibits RA FLS proliferation. The present study demonstrated that SMI can restore apoptosis of RA FLS cultured with RPS. These results indicate that SMI may have a potential role in the treatment of synovial hyperplasia of RA.

Analysis of clinical evaluation of response to treatment of Parkinson's disease with integrated Chinese and Western medicine therapy.

OBJECTIVE: To analyze the clinical evaluation of Parkinson's disease (PD) patients receiving integrated Chinese and Western medicine therapy. METHODS: One hundred and twenty patients were enrolled and randomly allocated to a control group or treatment group. Patients in the two groups received placebo and Bushen Huoxue Granule (, BHG), respectively. Both groups received baseline levodopa and benserazide (Madopar). The effects of treatment were assessed monthly during the 9-month treatment. Means of evaluation included Unified PD Rating Scale (UPDRS) scores (II and III), sleep scale score, 10 m turn back test (getting up time, 10 m×2 times, and turning time), timing motor test (TMT)-left and TMT-right, which were treated as the dependent variables; and age, sex, duration of PD, Hoehn and Yahr (H-Y) stage and Madopar dosage of admitted PD patients were as the independent variables. Multiple linear regression was used to analyze these factors. RESULTS: H-Y stage significantly affected UPDRS II score, UPDRS III score, and getting up time (P<0.01). Madopar dosage and H-Y stage significantly affected the 10 m×2 times (P<0.05 or <0.01). Madopar dosage significantly affected the sleep scale score (P<0.05). There were also significant correlations between age and TMT-left or TMT-right (P<0.01), and duration of PD and TMT-right (P<0.05). CONCLUSIONS: The six assessed means of clinical evaluation (including UPDRS II and UPDRS III scores, sleep scale score, getting up time, 10 m×2 times, and turning time) are sensitive indexes in all PD patients. H-Y stage and Madopar dosage are the major factors influencing means of clinical assessment of PD treatment.

Effectiveness of Bushen Huoxue Granule (补肾活血颗粒) on 5-serotonin and norepinephrine in the brain of Parkinson's disease patients with depressive state.

OBJECTIVE: To observe the clinical curative effect of Chinese medicine Bushen Huoxue Granule(补肾活血颗粒, BHG) on Parkinson's disease (PD) patients with depressive state. METHODS: Sixty-two PD patients with depressive state were randomly assigned to two groups by using a random number table, 31 in each group. Madopar was given to all as the conventional treatment. The fluoxetine hydrochloride dispersible tablet was given to the patients in the control group and BHG was given to those in the treatment group. The therapeutic course for all was 12 weeks. Before and after treatment, Hamilton depression rating scale (HAMD) was applied to judge the curative effect, and the changes of cerebral neurotransmitters levels in the brain of patients were detected by encephalofluctuograph technique. RESULTS: The scores of HAMD in the two groups were decreased markedly after 12-week treatment. It was lower in the treatment group than that in the control group with significant difference (P<0.01). The contents of norepinephrine (NE) and 5-serotonin (5-HT) in the PD patients were obviously lower than normal value. There was no significant difference between the two groups before treatment (P>0.05). The contents of NE and 5-HT were all increased in the two groups after treatment (P<0.05), with significant differences between the two groups (P<0.01). CONCLUSION: BHG could increase the contents of NE and 5-HT in PD patients' brain to improve the depressive state of PD patients.

Evaluation of the antioxidant activity and antiproliferative effect of the jaboticaba (Myrciaria cauliflora) seed extracts in oral carcinoma cells.

It is becoming increasingly evident that certain phytochemicals possess cancer chemopreventive properties. In this study, the antiproliferative activity of extracts from different parts of the jaboticaba (Myrciaria cauliflora) plant was evaluated for its effect on human oral carcinoma cell lines. The cytotoxicities of various plant extract concentrations were examined and the 50% maximal inhibitory concentration (IC50) was determined. Water extracts of jaboticaba seeds showed concentration-dependent antiproliferative effects. Annexin V/propidium iodide positivity with active caspase-3 induction indicated that the treated cells underwent apoptosis. Several important regulatory proteins (Bcl-2, Bcl-xL, Bid, and survivin) involved in apoptosis were also evaluated. The antioxidant activity of jaboticaba was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, and the drug concentration eliciting 50% maximum stimulation (SC50) was determined. The present findings suggest that water extracts of jaboticaba seeds exhibit an antiproliferative effect against oral cancer cells by inducing apoptosis through downregulating survivin expression and thereby activating caspase-mediated Bid cleavage.

Effect of modified Zhuye Shigao Decoction and its components on preventing radiation esophagitis of rats.

OBJECTIVE: To investigate the effect of Modified Zhuye Shigao Decoction (MZSD) and its components on preventing radiation esophagitis of rats. METHODS: One hundred Wistar rats were randomly divided into 5 groups, including the control group, radiation model group, MZSD group, Zhuye Shigao Decoction (ZSD) group, and added ingredients group, 20 rats in each group. The model of radiation esophagitis of rat was established by once local radiation of 40 Gy (330 Mu/min) with a high energy linear accelerator. The administration of Chinese medicine was continued for 14 days from 7 days before radiation application in the three treatment groups. On the 7th and 14th day, the serum was isolated and the levels of inflammatory cytokines tumor necrosis factor (TNF-α), interleukin 1ß (IL-1ß) and IL-8 were tested. The pathological slices of esophagus were obtained, and the pathological changes were observed. During the whole process, weight and food intake were recorded each day. RESULTS: On the 7th day after radiation, the esophagus of rats in the MZSD group was almost intact, and the pathological injury score was significantly lower than that of the radiation model group, ZSD group and added ingredients group (P<0.01). Compared with the control group, the body weight and food intake of rats in the radiation model group were significantly decreased, and the levels of TNF-α, IL-1ß and IL-8 were significantly increased (P<0.05 or P<0.01), while the MZSD group showed a significant increase in body weight and food intake, and a significant decrease in the levels of TNF-α, IL-1ß and IL-8 compared with the radiation model group, ZSD group and added ingredients group (P <0.05 or P<0.01). CONCLUSION: MZSD prevents the development of radiation esophagitis probably by inhibiting the generation and release of the inflammatory cytokines TNF-α, IL-1ß and IL-8.

[Clinical research on supplementing Qi and activating blood circulation herbs on lung protection in acute lung injury ventilation patients].

OBJECTIVE: To study the supplementing Qi and activating blood circulation herbs on lung protection in acute lung injury (ALI) ventilation patients. METHODS: 67 cases of ALI patients were enrolled and randomly divided into two groups. Routine treatment was for 32 cases of control group while treatment with adding supplementing Qi and activating blood circulation herbs was for 35 cases of treatment group, by 60 mL per time for 14 consecutive days with each day three times. Hemodynamics, changes of arterial blood gas, assay of pdymorphonuclears (PMN) value and the image of bronchoscopes between two groups in T0, T3, T7 and T14 were compared. RESULTS: PMN, HR, SVR, PaO2 , PO2/FiO2 and pH of treatment group were significantly improved compared with control group during T0, T3, T7 and T14 (P <0. 05). The compared differences were remarkable on hemodynamics, changes of arterial blood gas and assay of PMN value between treatment group and control group. The image of bronchoscopes in treatment group was improved significantly. CONCLUSIONS: The intervention of supplementing Qi and activating blood circulation herbs can effectively protect the lung function from ALI patients who received ventilation.

Cylindroside A, a new triterpenoid saponin from Cylindrokelupha dalatensis and its cytotoxic activity.

A new triterpenoid saponin, named cylindroside A (1), was isolated from the seeds of Cylindrokelupha dalatensis (Kosterm.) T.L. Wu by using chromatographic method. The structure of 1 was established by comprehensive spectroscopic analysis and chemical degradation. Compound 1 displayed significant antitumor activity in vitro against BCG and MCF-7 cancer cell lines and IC50 values were 4.17 ± 0.23 and 3.07 ± 0.66 µM by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, respectively.

Differences in the origin of philosophy between Chinese medicine and Western medicine: Exploration of the holistic advantages of Chinese medicine.

To explore advantages of Chinese medicine (CM) by analyzing differences in the origin of philosophy for human health between CM and Western medicine (WM). Methodologically, a distinctive feature of CM is its systems theory, which is also the difference between CM and WM. Since the birth of CM, it has taken the human body as a whole from the key concepts of "qi, blood, yin-yang, viscera (Zang-Fu), and meridian and channel", rather than a single cell or a particular organ. WM evolves from the Western philosophic way of thinking and merely uses natural sciences as the foundation. The development of WM is based on human structures, or anatomy, and therefore, research of WM is also based on the way of thinking of decomposing the whole human body into several independent parts, which is the impetus of promoting the development of WM. The core of CM includes the holistic view and the dialectical view. Chinese herbal medicines contain various components and treat a disease from multiple targets and links. Therefore, Chinese herbal medicines treat a diseased state by regulating and mobilizing the whole body rather than just regulating a single factor, since the diseased state is not only a problem in a local part of the body but a local reflection of imbalance of the whole body.

[Effects of danshen injection on the proliferation of rheumatoid arthritis fibroblast-like synoviocytes cultured with human serum].

OBJECTIVE: To investigate the effects of Danshen Injection (DSI) on the proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs) cultured in RA patients' serum. METHODS: The RA FLSs harvested from RA patients' synovial fluid were primarily cultured by routines. The cells were cultured with 10% inactivated human serum (the healthy human serum and the RA patients' serum) for 24 h. Then DSI at the final concentration of 0. 4 mg/mL was added in the cells for further 24 h culture. By taking 10% fetal calf serum as the control, the morphological changes were observed under optical microscope. The proliferation was analyzed by MTT. The apoptosis was detected by flow cytometry. The total RNA was extracted and reverse transcription was performed. The Bax mRNA expression was detected by fluorescent quantitative PCR. RESULTS: (1) After human serum was added in the healthy human serum and RA patients' serum, cells could grow adhering to the wall. Compared with the fetal calf serum group (FCS), the cell density was higher in the healthy human serum group than in the fetal calf serum group, with no obvious morphological changes. (2) MTT results showed that, compared with the fetal calf serum group, the absorbance value (OD) obviously increased in the healthy human serum group and the RA patients' serum group, showing statistical difference (P <0.01). After adding DSI at the final concentration of 0.4 mg/mL, cells from different serums were inhibited to various degrees (with OD significantly decreased, P <0.05). The OD value significantly increased more in the healthy human serum group and the RA patients' serum group than in the fetal calf serum group, showing statistical difference (P <0.01). There was statistical difference between the healthy human serum group and the RA patients' serum group (P <0.01). (3) The apoptosis rate in the RA patients' serum group obviously decreased with statistical difference, when compared with the Salvia miltiorrhiza free fetal calf serum group (P >0. 01). The apoptosis rate in the fetal calf serum group and the RA patients' serum group significantly increased after adding 0.4 mg/mL Salvia miltiorrhiza, showing statistical difference when compared with the Salvia miltiorrhiza free fetal calf serum group and the Salvia miltiorrhiza free RA patients' serum group (P <0.05). The FLSs were effected by 0.4 mg/mL Salvia miltiorrhiza, the apoptosis rate significantly decreased in the healthy human serum group and the RA patients' serum group, showing statistical difference when compared with the fetal calf serum group (P <0. 05, P <0.01). (4) The expression of Bax gene significantly increased in the RA patients' serum group and the fetal calf serum group after action of 0.4 mg/mL Salvia miltiorrhiza, showing statistical difference (P <0. 01). When 0.4 mg/mL Salvia miltiorrhiza was added, the expression of Bax mRNA obviously increased in the healthy human serum group and the RA patients' serum group, showing statistical difference when compared with the fetal calf serum group (P <0.01). CONCLUSIONS: (1) Although healthy human serum can be favorable to the growth of RA FLSs, the fetal calf serum could reflect the actual results better in the cyto biological research on specific diseases (if there is no serum from patients with corresponding disease). (2) DSI could inhibit the proliferation of RA FLSs through promoting their apoptosis.