This study aims to investigate the regulatory effects of Astragalus polysaccharide(APS) and APS combined with 5-fluorouracil(5-FU) on indoleamine-2,3-dioxygenase(IDO1) in the colon tumor microenvironment. Sixty Balb/c mice were randomized into a blank group, a model group, an APS group, an APS + 5-FU group, an APS + low-dose 5-FU group, and a 5-FU group. A tumor model was established by subcutaneous transplantation with CT-26 mouse colon cancer cells in other groups except the blank group. After successful modeling, each group was treated with corresponding drugs for 7 days. The general condition, body weight, and tumor volume of the mice were observed and measured daily during the treatment period. The mice were sacrificed at the end of treatment, and the tumor suppression rate and spleen index of the mice were calculated. Western blot and fluorescence quantitative PCR were employed to determine the protein and mRNA levels, respectively, of IDO1 in the tumor tissue of mice. High performance liquid chromatography was employed to measure the levels of tryptophan(Trp) and kynurenine(Kyn) in the tumor tissue of mice. Hematoxylin-eosin(HE) staining was performed to observe the histological changes of the tumor tissue, and immunohistochemistry to detect the changes of CD4 and CD8 expression in the tumor tissue. Compared with that in the model group, the tumor volume of mice in each treatment group significantly reduced. The body weights of mice in APS + 5-FU group and 5-FU group significantly reduced from day 4 to day 7 of treatment. In addition, the APS + 5-FU group and 5-FU group showed significantly decreased spleen index. The protein and mRNA levels of IDO1 were significantly down-regulated in the APS, APS + 5-FU, and APS + low-dose 5-FU groups. The drug interventions significantly increased the Trp content and decreased the Kyn content. The APS + 5-FU group showed significantly reduced infiltration of CD4~+ T lymphocytes and increased infiltration of CD8~+ T lymphocytes. APS inhibited the expression of IDO1 in the colon tumor microenvironment to increase CD8~+ T lymphocyte infiltration, and the combination of APS with 5-FU demonstrated better effect.
Mice ; Animals ; Tumor Microenvironment ; Colonic Neoplasms/genetics* ; Fluorouracil/pharmacology* ; Polysaccharides/pharmacology* ; CD8-Positive T-Lymphocytes/metabolism* ; RNA, Messenger/metabolism*

The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.
Humans ; Blood-Brain Barrier ; Liposomes ; Micelles ; Drug Delivery Systems ; Biological Transport ; Brain ; Brain Diseases

Solid preparations account for more than 50% of traditional Chinese medicines(TCM). TCM powder is an important raw material for solid preparations of TCM. Its powder properties directly affect the quality of solid preparations, and even clinical safety and effectiveness. Particle design technology based on the characteristics of powder in TCM is an important means to improve and enhance the quality of solid preparations. This study summarized the relevant principles, methods, characteristics, classification, equipment, and other elements of particle design technology in recent years, analyzed the difficulties in its application in the field of TCM powder, and proposed the strategies in conjunction with the development of computer data mining. The present study is expected to provide a reference for the suitability of particle design in the field of TCM powder.
Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Powders ; Technology

Targeting the deficiencies of Lingzhu Powder, this study introduced the particle design technology to improve its quality. Based on the mechanism of particle design for powder and the characteristics of solvent evaporation method, composite particles consisting of Succinum, Cinnabaris, and artificial Bovis Calculus were prepared. And the powder properties of composite particles and physical mixtures as well as the content uniformity of toxic components were investigated for exploring the technological advantages of particle design in improving the quality of Lingzhu Powder. The results showed that the composite particles prepared using solvent evaporation method and particle design technology were micro-particles, and the stable agglomerate structure could be observed under SEM. Composite particles exhibited better fluidity and compliance in oral intake than physical mixtures. The differences in chromatism, bulk density, and content uniformity of the composite particles were smaller than those of physical mixtures, and the corresponding RSD values \[4.8%, 1.8%, 3.4%(bilirubin), and 0.63%(HgS), respectively\] were smaller. The solvent evaporation combined with particle design technology can be utilized to significantly improve the quality of Lingzhu Powder, which has provided new ideas for the optimization of the quality of traditional Chinese medicinal powder.
Particle Size ; Powders ; Solvents ; Technology

Due to the complex source and different physical and chemical properties of traditional Chinese medicines(TCM) powder, there are many common pharmaceutical problems in its preparation, such as large particle size difference, poor mixing uniformity, and poor compliance with oral intake, which has directly affected the quality of solid preparations as well as their clinical efficacy and safety. This study observed the property of Zhuhuang Chuihou Powder and extract its pharmaceutical defects. It was found that realgar and calcined Borax in Zhuhuang Chuihou Powder were heavy in texture and toxic, and they were easy to be isolated, indicating the potential safety hazard. At the same time, Coptidis Rhizoma and Phellodendri Chinensis Cortex were the main sources of its bitterness. Therefore, based on the idea of "drug-excipients unity", the particle design technology was used to prepare core/shell-type composite particles with bitter medicines as the core and mineral medicines as shell. Both infrared spectroscopy and scanning electron microscopy results indicated the formation of composite particles, and the taste of these composite particles were improved. Compared with the physical mixtures, the composite particles exhibited significantly decreased RSD values in the content uniformity of berberine hydrochloride, arsenic disulfide, and sodium tetraborate and appearance uniformity. The introduction of particle design technology solved the problem of uneven dispersion of Zhuhuang Chuihou Powder, thus ensuring its uniform dispersion, stability, and control and improving the quality of the original preparation. This has provided a scientific basis for the quality control of TCM powder.
China ; Drugs, Chinese Herbal ; Particle Size ; Powders ; Taste

Targeting the poor powder characteristics of the contents in Hewei Jiangni Capsules, this study characterized the powder properties of the contents and employed particle design technique for improving the content quality. The content composite particles of Hewei Jiangni Capsules prepared by the particle design technique were evaluated by scanning electron microscopy(SEM), followed by infrared ray(IR), content uniformity, and in vitro dissolution detection. It was found that there was a good correlation between the crushed particle size of slices and the crushing time, and the calcined Haematitum was responsible for the poor content uniformity. After the fine powder of calcined Haematitum was super-finely ground for 8.5 min and those of the other contents in the capsule for 1 min, they were prepared into the composite particles, whose property characterizations were compared with those of the physical mixtures. The content uniformity of the prepared composite particles was significantly improved, and the preparation process was stable and reliable. The adoption of particle design technology to correct the poor uniformity of the physical mixture, solve the pharmaceutical defects of Hewei Jiangni Capsules, and improve the quality of prescriptions has provided important reference for the clinical application and development of Chinese medicinal preparations.
Capsules ; Microscopy, Electron, Scanning ; Particle Size ; Powders

Based on the defects in powder properties of the contents of Ziyin Yiwei Capsules, this study screened out the main medicinal slice powders causing the poor powdery properties, and introduced the powder modification process to improve the powdery properties of these slice powders, the pharmaceutical properties of the capsule contents, and the content uniformity of Ziyin Yiwei Capsules, so as to provide a demonstration for the application of powder modification technology to the preparation of Chinese medicinal solid preparations. Through the investigation on the powder properties of the contents of Ziyin Yiwei Capsules, it was clarified that the pulverized particle size of the capsule contents had a good correlation with the pulverization time. According to the measurement results of the powder fluidity and wettability, the quality defects of the capsule contents were caused by the fine powders of Taraxaci Herba and Lungwortlike Herba. "Core-shell" composite particles were prepared from medicinal excipients magnesium stearate and fine powders of Taraxaci Herba and Lungwortlike Herba slices after ultra-fine pulverization to improve the powder properties of the problematic fine powders. Powder characterization data including fluidity and wettability were measured, followed by scanning electron microscopy(SEM) and infrared ray(IR) detection. It was determined that the optimal dosage of magnesium stearate was 2%, and the compositing time was 3 min. The composite particles were then used as content components of the Ziyin Yiwei Capsules. The powder characteristics between the original capsule and the modified composite capsule including the particle size, fluidity, wettability, uniformity of bulk density, and uniformity of chromatism as well as the content uniformity and in vitro dissolution were compared. The results showed that the powder characteristics and content uniformity of the prepared composite capsule were significantly improved, while the material basis of the preparation was not changed before and after modification. The preparation process was proved to be stable and feasible. The powder modification technology solved the pharmaceutical defects that were easy to appear in the preparation of traditional capsules, which has provided experimental evidence for the use of powder modification technology for improving the quality of Chinese medicinal solid preparations and promoting the secondary development and upgrading of traditional Chinese medicinal dosage forms such as capsules.
Capsules ; Excipients ; Particle Size ; Powders ; Wettability

OBJECTIVETo study the effect of astrocyte exosomes on hypoxic-ischemic neurons.

METHODSRat astrocytes were cultured in vitro, and differential centrifugation was used to obtain the exosomes from the cell supernatant. Transmission electron microscopy, Nanosight, and Western blot were used for the identification of exosomes. BCA method was used to measure the concentration of exosomes. Rat neurons were cultured in vitro and then divided into control group, exosome group, oxygen glucose deprivation (OGD) group, and OGD+exosome group (n=3 each). The OGD and OGD+exosome groups were cultured in glucose-free medium under the hypoxic condition. The exosome and OGD+exosome groups were treated with exosomes at a final concentration of 22 μg/mL. The control and OGD groups were given an equal volume of phosphate-buffered saline. ELISA was used to measure the level of lactate dehydrogenase (LDH) in neurons. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure the apoptotic index of neurons.

RESULTSThe identification of exosomes showed that the exosomes extracted by differential centrifugation had the features of exosomes. Compared with the control and exosome groups, the OGD group had significant increases in LDH level and apoptotic index (P<0.05). Compared with the OGD group, the OGD+exosome group had significant reductions in LDH level and apoptotic index (P<0.05).

CONCLUSIONSThe exosomes from astrocytes have a protective effect on neurons with hypoxic-ischemic injury.

Animals ; Apoptosis ; Astrocytes ; physiology ; Cell Hypoxia ; Cells, Cultured ; Exosomes ; physiology ; Glucose ; deficiency ; Hydro-Lyases ; analysis ; Neuroprotection ; Rats ; Rats, Sprague-Dawley

Objective: To study the safety and efficacy of Bushen Daozhuo Granules (BDG) in the treatment of type Ⅲ prostatitis. METHODS: This multicenter randomized controlled clinical trial included 478 patients with type Ⅲ prostatitis, 290 in the trial group and 188 as controls, the former treated with BDG at 200 ml bid and the latter with tamsulosin hydrochloride sustainedrelease capsules at 0.2 mg qd, both for 4 weeks. Before treatment, after 4 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the NIH Chronic Prostatitis Symptom Index (NIHCPSI) scores and compared the safety and effectiveness rate between the two groups of patients. RESULTS: Compared with the baseline, the NIHCPSI score was markedly decreased in the control group after 4 weeks of medication (21.42 ± 4.02 vs 15.67 ± 3.65, P < 0.05) but showed no statistically significant difference from that at 4 weeks after drug withdrawal (19.03 ± 3.86) (P>0.05), while the NIHCPSI score in the trial group was remarkably lower than the baseline both after 4 weeks of medication and at 4 weeks after drug withdrawal (10.92 ± 2.06 and 12.91 ± 2.64 vs 21.58 ± 3.67, P < 0.05). The trial group exhibited both a higher rate of total effectiveness and safety than the control (P < 0.05). CONCLUSIONS BDG is safe and effective for the treatment of type Ⅲ prostatitis.
Capsules ; Chronic Disease ; Delayed-Action Preparations ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Male ; Prostatitis ; drug therapy ; pathology ; Sulfonamides ; adverse effects ; therapeutic use ; Tamsulosin ; Treatment Outcome ; Urological Agents ; adverse effects ; therapeutic use

OBJECTIVETo analyze the incidence of cytomegalovirus infection and related risk factors after allogeneic hematopoietic cell transplantation and to develop a rational strategy for the preemptive treatment of CMV infection.

METHODSThe clinical data of 398 patients undergoing allogeneic hematopoietic cell transplantation from December 2011 to December 2014 were analyzed retrospectively by using a Kaplan Meier analysis and Logistics model.

RESULTSOut of 398 patients 233 developed post-transplant CMV infection (58.5%). Univariate analysis showed that HLA mismatch, ATG administration, acute graft versus host disease (aGVHD), using prednisone ≥ 1 mg/kg body weight or equivalent were associated with increase of CMV infection. Multivariate analysis showed that HLA mismatch (HR = 2.765, P = 0.000), ATG administration (HR = 3.866, P = 0.000), using prednisone ≥ 1 mg/kg body weight or equivalent (HR = 4.767, P = 0.000) also were associated with increase of CMV infection.

CONCLUSIONHLA mismatch, ATG administration, using prednisone ≥ 1 mg/kg are risk factors for CMV reaction.

Cytomegalovirus Infections ; diagnosis ; epidemiology ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Incidence ; Kaplan-Meier Estimate ; Logistic Models ; Multivariate Analysis ; Prednisone ; administration & dosage ; Retrospective Studies ; Risk Factors