Dioscoreae Rhizoma formula granules are made from decoction pieces by decocting， extracting， separating， concentrating， drying and granulating， which have the advantages of simple dispensing， convenient use and easy to take without decoction. However， because Dioscoreae Rhizoma is rich in starch and mucus components， its extract powder and formula granules are poorly soluble and difficult to dissolve or disperse completely within 5 min， and the insoluble material is difficult to dissolve completely even after 24 h in water， which affects the quality evaluation of the formula granules and medication psychology of patients. Therefore， by studying the dissolution process and mechanism of Dioscoreae Rhizoma extract and its formula granules， it was found that the special chemical composition of Dioscoreae Rhizoma， the denaturation of starch and its compounding with protein and other substances during the high temperature extraction process， and the contraction of coating membrane during the spray drying process were combined to form the special microstructure of coating membrane covering starch granules， and it is the root cause of poor solubility of Dioscoreae Rhizoma formula granules. Based on the research on the structure， property and function of the powder， this paper proposed a technical strategy to improve the solubility of Dioscoreae Rhizoma formula granules by powder modification process， and experimentally demonstrated that the modified Dioscoreae Rhizoma formula granules could completely dissolve within 2 min， which solved the technical problem and could provide reference for the improvement of solubility of other similar varieties， and promote the high-quality development of traditional Chinese medicine formula granule industry.

A dry suspension of Indigo Naturalis (IN) based on lactose-IN composite particles was designed by powder modification technology to meet the clinical needs of IN. The contact angle was used as an evaluation index to investigate the effects of the type of modifier lactose, the amount of lactose, and the co-grinding time of lactose and IN on the hydrophilicity of IN. The difference between IN before and after modification was compared through physical properties such as particle size and scanning electron microscope, as well as hydrophilic properties such as surface free energy and multiple light scattering. The optimal process of lactose-IN composite particles is as follows: after lactose is ground alone for 2 minutes, it is co-ground with IN at a ratio of 1∶1 for 6 minutes. The results of the investigation of powder properties show that the particle size d_0.9 of IN is reduced from 112.75 μm to 87.30 μm after modification. The BET and Langmuir specific surface areas decreased by 8.661 m²·g^-1 and 12.512 m²·g^-1, respectively. SEM shows that lactose is attached to the surface of modified IN (MIN); surface element analysis shows that Si, Ca, and Mg elements of MIN are smaller than IN, and O elements are larger. The infrared spectrum shows that the MIN possesses the characteristic peaks of both IN and lactose. Compared MIN with IN, the contact angle and the non-polar surface free energy decreased by 35.1° and 9.975 mJ·m^-2, respectively; the polar surface free energy and the surface free energy increased by 36.956 and 26.950 mJ·m^-2, respectively. The results of multiple light scattering showed that the light transmittance of MIN was 35% lower than that of IN, and the backscattered light intensity was increased by about 25%. Only one excipient was used to successfully prepare IN dry suspension with good wettability and suspending property, which provided a basis for the development of new preparations of IN.

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) μm to(37.91±0.42) μm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.
Powders ; Solubility ; Technology, Pharmaceutical ; Technology ; Plant Extracts ; Particle Size

Galli Gigerii Endothelium Corneum (GGEC) is a commonly used traditional Chinese medicine for digestion. Its odor is unpleasant, which decreases children's compliance with taking this traditional medicine. Traditional processing methods utilize heat processing methods such as stir-frying and vinegar processing to deodorize the medicine, but this affects the activity of digestive enzymes, so there is a need to find a new method for removing the fishy odor while retaining the beneficial effect of GGEC. Here we have developed the use of supercritical CO₂ low-temperature fluid extraction to eliminate the odor while retaining the medicinal benefits. Headspace-solid-phase microextraction-gas chromatography-triple quadrupole mass spectrometry (HS-SPME/GC-QQQ-MS/MS) combined with the gas activity value method was used to determine compositional differences in the product before and after supercritical CO₂ extraction and separation. Then, based on the sensory evaluation of volunteers, combined with the analysis of volatile components, the fishy odor intensity and the types of fishy odorants were compared between the raw product, stir-fried product, vinegar product and the supercritical CO₂ extract. Pepsin and amylase activity were used to compare the differences in the digestive enzyme activities with the four forms of GGEC, and Fourier transform infrared spectroscopy (FT-IR) was used to compare the differences in the structure. We compared the content of total amino acids, digestive amino acids and bitter amino acids, and an animal model of delayed gastric emptying in mice with soybean oil, based on a phenol red indicator, was used to determine differences in the efficacy of gastric emptying in vivo. The results show that the fishy odor of GGEC powder is significantly reduced after supercritical extraction, and the substances that contribute the fishy odor are only 12.8% of the raw material. The results of FT-IR analysis show that the supercritical extract of GGEC is not changed in its material structure compared with the raw product. The digestive enzyme activity titers showed that amylase and pepsin activity in the raw products are about 3.9 and 1.4 times higher than those of stir-fried products and vinegar products. The activity titers of amylase and pepsin in the supercritical CO₂ extracts are about 2.7 and 1.3 times higher than those of stir-fried products and vinegar products, and there was no significant difference in the content of digestive-promoting amino acids in the four types of GGEC. The in vivo validation experiment showed that the average gastric emptying rates of the mice in the raw product group, the supercritical extract group, the stir-fried product group, and the vinegar product group were 69%, 59%, 40% and 51%, respectively. Compared with the stir-frying method and the vinegar-simmering method, the supercritical CO₂ fluid extraction method retained the gastric emptying effect of GGEC. In general, the supercritical CO₂ fluid low-temperature extraction method removes the fishy odor of GGEC as compared with the traditional stir-frying method and vinegar method, and retains the biologically active components and the effect on digestion of GGEC.

Based on the principle of particle design, the powder of Xiaojin Pills was prepared, and the quality uniformity was investigated by means of powder characterizations and content uniformity. By studying the mixed crushing rules of the classified materials and the design principle of the powder particles of Chinese medicine, the powder of the Xiaojin Pills was prepared. At the same time, the manmade mixed powder and the control powder prepared by pharmacopoeia were prepared. The mixed homogeneity of the three powders was evaluated by particle size distribution and color difference. The GC-MS and LC-MS/MS were used to study the homogeneity of their contents. The best preparation process of particle design powder is:materials easily crushed are smashed for 50 min in the vibrating ultrafine mill with -15℃, then add the materials difficultly crushed into the mill and let them crushed together for 3 min. The particle size range of manmade mixed powder was the largest with the particle size difference being more than 100 microns, the RSD value being 26.07%. The particle size range was more than 50 microns in the powder prepared by pharmacopoeia, and the RSD was nearly 15%. The difference in particle size was only around 4 μm and the RSD value was 3.18%. The color difference test showed that the composite chromatism (dE^*) value of the powder prepared by pharmacopoeia was the largest for the RSD was 84.56%. The RSD of manmade mixed powder and the powder prepared by Pharmacopeia were 53.83% and 32.83%, respectively. The RSD value of the particle designed powder's muscone content is about 50% of the other two kinds of powders. The contents of 10 components in powders were determined by LC-MS/MS. The RSD values of the particle designed powder were much smaller than other two kinds of powders. Results indicate that the uniformity of the particle designed powder is better than other two kinds of powders. Chinese medicine particle design technology can effectively improve the uniformity of traditional Chinese medicine powder.

Objective To explore the difference in gastric residual volume (GRV) between singledose and split-dose bowel preparation before colonoscopy under general anesthesia.Methods From October 8th to December 30th in 2016,the out-patients undergoing gastroscopy and colonoscopy with anesthesia services on the same day were selected and divided into the traditional single-dose bowel preparation group and split-dose bowel preparation group.The GRV and intestinal preparation quality were compared between the two groups.T test was used for statistical analysis and multiple linear regression analysis was performed for the influence factors of GRV analysis.Results A total of 121 patients were enrolled,60 patients in the spilt-dose bowel preparation group and 61 in the traditional single-dose bowel preparation group.The mean GRV of the split-dose bowel preparation group was (17.3 ± 12.2) mL,which was lower than that of the single-dose bowel preparation group ((23.7 ± 14.6) mL),and the difference was statistically significant (t =2.642,P=0.009).The score of intestinal preparation quality of the split-dose bowel preparation group was 8.05 ± 0.85,which was higher than that of the single-dose bowel preparation group (7.67±1.19),and the difference was statistically significant (t =-2.002,P=0.048).Fasting time was related with GRV (odd ratios (OR)=1.732,95％ contidence interval (CI) O.299 to 3.168,P=0.018).Conclusion The GRV of patients with split-dose bowel preparation before colonoscopy is lower than that of traditional single-dose bowel preparation,thus reducing the risk of aspiration during anesthesia.

Objective To explore the screening of peroxisome pathway reactive oxygen species (ROS) oxidative stress gene and its correlation with the antitumor sensitivity of artesunate against pancreatic cancer. Methods Based on microarray mRNA expressions of 55 tumor cell lines in the National Cancer Institute common database,peroxisome pathway-related key genes which were significant correlation with half-inhibitory concentration (IC50 )values of artesunate antitumor activity against human pancreatic cancer were selected by Kendall test.The candidate genes associated with artesunate sensitivity were identified and their mRNA expressions in pancreatic cancer cells were tested using fluorescent quantitative PCR.The contents of peroxi-dase in pancreatic cancer cells were detected through the DAB staining.Results Thirteen key genes mRNA expressions in peroxidase pathways were significantly correlated with IC50 values for artesunate antitumor activi-ty.Compared with normal liver cells HL-7702 (1.00),CRAT (2.89 ±0.06),PEX11B (1.90 ±0.07)and PEX16 (1.35 ±0.07)mRNA expression levels were significantly increased in pancreatic cancer Panc-1 cells which sensitive to artesunate (t =33.00,P <0.01;t =17.85,P <0.01;t =4.54,P <0.05).While CAT
(1.43 ±0.03),SOD1 (2.07 ±0.04)and SOD2 (1.15 ±0.01)mRNA expression levels were also signifi-cantly increased in Panc-1 cells which sensitive to artesunate (t =11.71,P <0.01;t =35.85,P <0.01;t =13.22,P <0.01).However,PEX12 (0.51 ±0.02),CAT (0.47 ±0.02),PRDX1 (0.43 ±0.01),and SOD1 (0.44 ±0.01)mRNA expression levels in pancreatic cancer BXPC-3 cells which resistant to artesunate were significantly lower than that of HL-7702 cells (t =37.53,P <0.01;t =16.52,P <0.01;t =84.20, P <0.01;t =48.24,P <0.01).DAB staining showed that the positive expression rate of peroxisomal content was apparently higher in Panc-1 cells (61.5%)than that of HL-7702 cells (43.8%),with a significant difference (χ2 =16.11,P <0.01).Conclusion Peroxisome and its related ROS antioxidant enzymes CAT, PRDX1,SOD gene expression may be the important factors that affect artesunate antitumor activity against human pancreatic cancer.

It has been proved that FAS is a potent oncogene. Its expression and activity is normal in most of the non-neoplastic cells, but it is over-expressed and associated with poor prognosis in several human malignancies. Recent studies show that FAS inhibitor can induce significant anti-tumor effect. It reduces cell proliferation,enhances apopto-sis,inhibits tumor invasion and metastasis,while it is also an chemosensitization for other chemotherapy drugs. In this paper, the anti-tumor mechanism of FAS inhibitors is reviewed to prospect the research direction of its anti-tumor ef-fect.

ObjectiveTo investigate the biological effects and its mechanisms of ascorbic acid on pancreatic cancer PANC1 cells. Methods PANC1 cells were treated by ascorbic acid of different concentrations (0 ～40 mmol/L) for 24,48,72 hours.The proliferation of PANC1 cells was analyzed by MTT method; cell cycle and apoptosis were assessed by flow cytometry (FCM); inverted microscopy and transmission electron microscopy were used to observe cell morphology. The membrane potential of mitochondria were mearured by with JC-1 staining and FCM.Meanwhile,the changes of cell morphology and mitochondrial membrane potential induced by ascorbic acid after pretreatment with hydrogen peroxidescavenging enzyme (catalase) and red blood cells were also detected. Results Ascorbic acid in pharmacologic concentrations selectively inhibited the proliferation of PANC1 cells in a dose and time dependent manner.PANC1 cells were arrested in G2/M phase after treatment with 5 mmol/L ascorbic acid [ (32.55 ± 7.14)％ vs (22.00 ±1.27)％,t =5.808,P＜0.05],but there was no changes on apoptosis rate [ (1.98 ± 1.80)％ vs (1.09 ±0.16)％ ].Inverted microscope and transmission electron microscopy showed that oncosislike cell death of PANC1 cells was induced after treatment with ≥5 mmol/L ascorbic acid.Mitochondrial membrane potential of PANC1 cells was significantly lower than that of the control group in a dose dependent manner.The descent of mitochondrial membrane potential was significantly inhibited by pretreatment with catalase and red blood cells,and the degree of cell oncosis was attenuated.ConclusionsAscorbic acid significantly inhibited the proliferation of pancreatic cancer PANC1 cells in vitro.Ascorbic acid induced PANC1 cell oncosis,but not apoptosis.The possible mechanisms of inducing oncosis may be related to the descent of mitochondrial membrane potential.

Objective To analyze the reliability of the Boston bowel preparation scale (BBPS) for the assessment of bowel preparation quality. Methods Demonstration video of Boston bowel preparation scale provided by Boston Medical Center were viewed by 49 clinicians,who came from several hospitals in Guangdong province and participated in an education conference.Then 3 testing colonoscopy videos were scored with BBPS and inter-observer reliability was assessed. 13 participants repeated the above test 3 months later,and intra-observer reliability was assessed.Results The correlation coefficient of inter-observer for BBPS scores was 0.987 (95％ CI:0.949 - 1.000 ),and that of intra-observer was 0.713(95 ％ CI:0.452 -0.849).Conclusion BBPS is a reliable measure of bowel preparation,while the validity of BBPS deserves further analysis.