Comparison of Plerixafor or Cyclophosphamide Combined with G-CSF in Mobilization of Peripheral Blood Stem Cells in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34+ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens.@*RESULTS@#The 41 patients underwent 97 mobilization collections, and the median number of CD34+ cells collected was 6.09 (0-34.07)×106/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34+ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34+ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34+ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05).@*CONCLUSION@#PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34+ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.

Impact of Particle Size on Density of Binary Powder Mixture of Chinese Medicine / 中国实验方剂学杂志

Objective:To investigate the influence of particle size on density of binary powder mixture of traditional Chinese medicine （TCM）， and to provide reference for formulation design of TCM preparations. Method:Three groups of binary powder mixtures with different particle size ratio （<italic>α</italic>） were constructed， namely Oroxyli Semen-microcrystalline cellulose PH102 （MCC PH102） （<italic>α</italic>=0.071 7）， Stellariae Radix-MCC PH200 （<italic>α</italic>=0.158 7） and Angelicae Sinensis Radix-MCC KG802 （<italic>α</italic>=0.840 6）. Binary powder mixtures with nine mass ratios （90∶10， 80∶20， 70∶30， 60∶40， 50∶50， 40∶60， 30∶70， 20∶80 and 10∶90） were prepared for each group， and 27 binary powder mixtures containing TCM were obtained. The particle size distribution， density and other parameters of six single materials and 27 binary powder mixtures were characterized. Based on the packing theory and multivariate analysis， the effects of particle size related parameters on the filling structure and density of the binary powder mixtures were elucidated. Result:The <italic>α</italic> of Angelicae Sinensis Radix-MCC KG802 binary mixture system was larger than the replacement rate （<italic>α</italic>_r=0.741 0）， and its density had a good linear relationship with the mass ratio， which conformed to the replacement mechanism. The <italic>α</italic> of Oroxyli Semen-MCC PH102 binary mixture system was smaller than the critical ratio （<italic>α</italic>_c=0.154 0）， and its density was nonlinear with the mass ratio of components， which conformed to the filling mechanism. The <italic>α</italic> of Stellariae Radix-MCC PH200 binary mixture system was between <italic>α</italic>_c and <italic>α</italic>_r， its density was affected by both of replacement mechanism and filling mechanism. Based on the partial least squares （PLS） model， the variable importance in the projection （VIP） analysis further proved that the mixing mass ratio （VIP value=1.62）， <italic>α</italic> （VIP value=1.13） and <italic>D</italic>₁₀ （the corresponding particle size when the particle size distribution accumulated to 10%， VIP value=1.06） were the key factors affecting the density of binary powder mixtures of TCM. Conclusion:In the binary powder mixtures of TCM， the linearity relationship between density and mass ratio is largely depended on particle size difference of components.

The influence of pressure range on the fitting results of tablet compression equation / 药学学报

According to the commonly used tablet compressibility, compactability and tabletability equation, the influence of pressure range on the fitting results and parameters of different compression equations was studied, and the optimal pressure range of different equations was determined. Plastic material microcrystalline cellulose (MCC) PH102, brittle material spray dried lactose and Chinese medicine Sanqi were used as experimental objects, the compression curves of tablets were obtained by the combination of dies with different diameters. For Heckel equation, the shape of Heckel section of different materials is not uniform, and the specified linear fitting range cannot be obtained, therefore, different distances between fitting pressure starting point and starting point were set to observe the influence of pressure range on R2 of Heckel equation. The Kawakita equation, Gurnham equation, Ryshkewitch-Duckworth (R-D) equation and Power equation are fitted in three different pressure ranges of 15-200, 15-300 and 15-400 MPa, respectively. In order to find the best linear region of Heckel equation, the 3D scatter diagram of "starting point of pressure, pressure range and R2" is drawn. The best linear pressure ranges of Heckel curves of MCC, lactose and Sanqi were 20-170, 20-220 and 10-90 MPa, respectively. It is proved that the 3D scatter diagram is an effective method to find the linear range of Heckel equation. The change of pressure range has little influence on the curve fitting effect and compression parameters of Kawakita equation, Gurnham equation and Ryshkewitch-Duckworth equation. The low pressure range of 15-200 MPa can meet the fitting requirements of Kawakita equation, Gurnham equation, R-D equation and Power equation for different materials. Therefore, only by optimizing the pressure range, can the good fitting effect be ensured and the obtained compression parameters be more reliable and interpretable.

Material manufacturability classification in high shear wet granulation process of Chinese medicine / 中国中药杂志

The high shear wet granulation(HSWG) process of Chinese medicine has a complicated mechanism. There are many influencing factors that contribute to this process. In order to summarize the manufacturability of different kinds of materials in HSWG, this paper constructed a material library composed of 11 materials, including 4 Chinese medicine extracts and 7 pharmaceutical excipients. Each material was described by 22 physical parameters. Several binders were employed, and their density, viscosity and surface tension were characterized. Combining empirical constraints and the principle of randomization, 21 designed experiments and 8 verification experiments were arranged. The partial least squares(PLS) algorithm was used to establish a process model in prediction of the median granule size based on properties of raw materials and binders, and process parameters. The surface tension and density of binders, as well as the maximum pore saturation were identified as key variables. In the latent variable space of the HSWG process model, all materials could be divided into three categories, namely the Chinese medicine extracts, the diluents and the disintegrants. The granulation of Chinese medicine extracts required low viscosity and low amount of binder, and the resulted granule sizes were small. The diluent powders occupied a large physical space, and could be made into granules with different granule sizes by adjusting the properties of binders. The disintegrants tended to be made into large granules under the condition of aqueous binder. The combination use of material database and multivariate modeling method is conducive to innovate the knowledge discovery of the wet granulation process of Chinese medicine, and provides a basis for the formulation and process design based on material attributes.

Mitochondrial DNA Heteroplasmy of Hair Shaft Using HID Ion GeneStudioTM S5 Sequencing System / 法医学杂志

Objective To study the heteroplasmy of the whole mitochondrial genome genotyping result of hair shaft samples using HID Ion GeneStudioTM S5 Sequencing System. Methods The buccal swabs and blood of 8 unrelated individuals, and hair shaft samples from different parts of the same individual were collected. Amplification of whole mitochondrial genome was performed using Precision ID mtDNA Whole Genome Panel. Analysis and detection of whole mitochondrial genome were carried out using the HID Ion GeneStudioTM S5 Sequencing System. Results The mitochondrial DNA sequences in temporal hair shaft samples from 2 individuals showed heteroplasmy, while whole mitochondrial genome genotyping results of buccal swabs, blood, and hair samples from the other 6 unrelated individuals were consistent. A total of 119 base variations were observed from the 8 unrelated individuals. The numbers of variable sites of the individuals were 29, 40, 38, 35, 13, 36, 40 and 35, respectively. Conclusion Sequence polymorphism can be fully understood using HID Ion GeneStudioTM S5 Sequencing system.

Apoptosis of gastric cancer MGC-803 cells induced by rosmarinic acid analogue-11 by inhibiting ERK/MAPK pathway / 中国药理学通报

Aim: To explore the apoptosis and mechanisms of human gastric cancer cells MGC-803 induced by RAA-11. Methods: MTT and colony assays were used to detect the survival of MGC-803 cells treated with RAA-11. The effect of RAA-11 on the apoptotic morphology of MGC-803 cells was observed by Hoechst 33258 staining. The effect of RAA-11 on the apoptosis rate of MGC-803 cells was detected with flow cytometry. The effects of RAA-11 on apoptosis related protein expression of caspase-3, Bcl-2 and Bax as well as pathway proteins ERK and p-ERK in MGC-803 cells were observed by Western blot. Results: MTT assay showed that the proliferation of MGC-803 cells was effectively inhibited in a time- and concentration-dependent manner (P <0. 01). The result of colony suggested that RAA-11 could inhibit the proliferation of MGC-803 cells. Hoechst 33258 staining indicated that the nucleus of MGC-803 cells had a typical apoptotic morphological change after intervention with RAA-11. The result of flow cytometry suggested that RAA-11 had a significant apoptotic effect on MGC-803 cells. The expressions of Bax and caspase-3 were significantly up-regulated (P <0. 01), and the expressions of Bcl-2, ERK and p-ERK were down-regulated (P <0. 01) in MGC- 803 cells treated with RAA-11. Conclusions: RAA-11 inhibits the proliferation and induces apoptosis in MGC-803 cells, which may be related to the inhibition of ERK/MAPK pathway.

Rosmarinic acid analogue-11 inhibited proliferation and migration of human gastric cancer MGC-803 cells via EGFR-JNK pathway / 中国药理学通报

Aim: To explore the effects of RAA-11 on the growth and migration of human gastric cancer cells MGC-803 via the EGFR-JNK pathway. Methods: The effect of RAA-11 on the activity of human gastric mucosa cells GES-1 and human gastric cancer cells MGC- 803 was observed by MTT assay. The effect of RAA-11 on the migration in human gastric cancer MGC-803 cells was detected by scratch test. The effect of RAA- 11 on EGFR mRNA expression in human gastric cancer MGC-803 cells was detected by qRT-PCR. The changes of apoptosis-related proteins caspase-3, Bcl-2, Bax as well as pathway proteins EGFR, JNK, and p-JNK expression in human gastric cancer MGC-803 cells were assessed by Western blot. Results: MTT results indicated that RAA-11 significantly inhibited the proliferation of MGC-803 cells in human gastric cancer compared with human gastric mucosa GES-1 cells (P < 0. 01), suggesting that RAA-11 had a selective effect on MGC-803 cells. The scratch result suggested that RAA-11 could suppress the migration of MGC-803 cells. The results of qRT-PCR indicated that RAA-11 decreased the expression level of EGFR mRNA in human gastric cancer MGC-803 cells. Western blot results suggested that RAA-11 up-regulated apoptosisrelated proteins caspase-3 and Bax in human gastric cancer MGC-803 cells, promoted the expression of pathway proteins JNK and p-JNK (P < 0. 01), downregulated the expression of apoptosis-related proteins Bcl-2, and reduced the expression level of pathway protein EGFR (P < 0. 01). Conclusions: RAA-11 can inhibit the proliferation and migration and induce apoptosis of human gastric cancer MGC-803 cells by the EGFR-JNK pathway.

Rosmarinic acid derivative RAD-9 induces apoptosis in gastric cancer MGC-803 cells via PI3K/Akt and p38 MAPK signaling pathway / 中国药理学通报

Aim To study the apoptosis-inducing effect of rosmarinic acid derivative RAD-9 on gastric cancer MGC-803 cells and the underlying mechanisms.Methods MTT assay was taken to detect the survival of gastric cancer MGC-803 cells effected by RAD-9.Cell apoptosis was detected by flow cytometry.The apoptotic morphology of MGC-803 cells was observed by Hoechst 33258 staining.The protein expression levels of Bcl-2,Bax,caspase-3,Akt,p-Akt,p38 MAPK and p-p38 MAPK were measured by Western blot.Results The results of MTT assay showed that RAD-9 inhibited the viability of gastric cancer MGC-803 cells in a time and concentration-dependent manner.Flow cytometry showed that RAD-9 significantly promoted apoptotic cell percentage in gastric cancer MGC-803 cells (P ＜ 0.01).Hoechst 33258 staining showed that the nucleus of MGC-803 cells could be observed with typical apoptotic morphological changes after RAD-9 administration.Compared with the control group,the protein expression levels of Bcl-2,Akt,p-Akt were significantly down-regulated (P ＜ 0.01),while those of Bax,caspase-3,p38 MAPK,p-p38 MAPK were significantly up-regulated (P ＜ 0.01).Conclusion RAD-9 can inhibit the growth and further induce apoptosis in gastric cancer MGC-803 cells,which may involve inhibiting PI3K/Akt and activating p38 MAPK signaling pathway.

In vitro study of genistein inducing apoptosis in MDA-MB-231 breast cancer cells via NF-κB and MAPK signaling pathways / 中国药理学通报

Aim To study the effect of genistein on apoptosis in human breast cancer MDA-MB-231 cells and the underlying mechanisms. Methods MTT as-say was used to observe the inhibitory rate on human breast cancer MDA-MB-231 cells treated with genistein. Colony assay was used to determine the cell colony formation rate on human breast cancer MDA-MB-231 cells treated with genistein. Western blot was used to detect the expression of Bcl-2, Bax, caspase-3,NF-κB, ERK, p-ERK, JNK and p-JNK in human breast cancer MDA-MB-231 cells treated with genistein. Results The results of MTT assay showed that genistein inhibited the viability of breast cancer MDA-MB-231 cells in a time- and concentration-de-pendent manner. Colony assay suggested that genistein had an antiproliferative effect on MDA-MB-231 cells. The expression levels of Bcl-2, NF-κB and p-ERK were significantly down-regulated compared with con-trol(P < 0.01). However, the expression of Bax, caspase-3 and p-JNK was significantly up-regulated(P<0.01). Conclusions Genistein could inhibit the growth of human breast cancer MDA-MB-231 cells and induce apoptosis,and the mechanism may be related to the inhibition of NF-κB, ERK/MAPK signaling path-ways and the activation of JNK/MAPK signaling path-way.