Objective: To understand the relationship between chloroquine resistance and the virulence of Plasmodium berghei. Met hods: Dynamic changes of histopathologic features of livers, spleens, brains, hearts, lungs and kidneys of mice infected with the chloroquine-sensitive (N) and the chloroquine-resistant (RC) strains of P. berghei were compared. Results: In mice infected with the N strain, deposition of heavy hemoz oin in livers and spleens, congestive edema in lungs, and congestion and embolis m in the brain capillaries were observed. The histopathologic features revealed ac ute inflammatory reaction. In mice infected with the RC strain, histopathologic variations of livers and spleens were associated with changes of parasitemia. In terstitial pneumonia was displayed in lungs. There were chronic histopathologic changes of the organs in the mice infected with RC strain. Conclusion: The mice infected by the N strain with potent virulence die due to adher ence of the erythrocytes to microvascular endothelia and embolism of the microva scula, especially in their brain. Immune responses of the mice infected by the R C strain with poor virulence may be a delayed-type hypersensitive inflammation a ssociated with CD4+Th1 at an early stage of the infection, but may become anti body-dependent immune response assisted with CD4+Th2, which play a key role in elimination of the malaria parasites at later stage of the infection.

Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.
Administration, Intravenous ; Animals ; Caffeic Acids ; pharmacokinetics ; Chromatography, Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Lactates ; pharmacokinetics ; Macaca mulatta ; Mass Spectrometry ; Plant Roots ; chemistry ; Salvia miltiorrhiza ; chemistry

To enhance the quality and efficiency of ozagrel by investigating the differences between the ozagrel polymorphs in bioavailability. Solid ozagrel in different polymorph forms were orally administered to SD rats. An HPLC method was established to determinate plasma level of ozagrel. The bioavailabilities of two polymorph forms were calculated and compared. The pharmacokinetic parameters of ozagrel, were as follows: Cmax was 32.72 ± 17.04 and 34.01 ± 19.13 mg · L(-1), respectively; AUC0-t was 61.14 ± 14.76 and 85.56 ± 18.08 mg · L(-1) · h, respectively; t½ was 1.53 ± 0.51 and 4.73 ± 3.00 h, respectively. There was no significant difference in pharmacokinetic parameters between form I and II polymorphs of ozagrel while the t½ of form II is longer, which indicates that the use of form II polymorph as pharmaceutical product may prolong the effective action time in clinics. This would help the polymorph quality control in drug production.
Animals ; Biological Availability ; Chromatography, High Pressure Liquid ; Methacrylates ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

Artificial intelligence technology is being widely applied in drug screening. This paper introduces the characteristics of artificial intelligence, and summarizes the application and progress of artificial intelligence technology especially deep learning in drug screening, from ligand-based and receptor structure-based aspects. This paper also introduces how to apply artificial intelligence to drug design from these two aspects. Finally, we discuss the main limitations, challenges, and prospects of artificial intelligence technology in the field of drug screening.

BACKGROUND: The clinical treatment of bone defects is facing many problems. In order to solve the problem, the development of scaffold materials for bone tissue engineering has been an issue of concern. OBJECTIVE: To review the clinical application and development prospect of biological scaffold materials and mesenchymal stem cells in bone tissue engineering. METHODS: PubMed and CNKI databases were retrieved for the articles regarding bone tissue engineering published from January 2000 to December 2016. The key words were "bone tissue engineering; biological scaffold; mesenchymal stem cells" in English and Chinese, respectively. Articles addressing biological scaffolds and mesenchymal stem cells were included, except for repetitive research and Meta-analysis articles.RESULTS AND CONCLUSION: Current biological scaffolds mainly include synthetic scaffold materials (polyvinyl alcohol, polylactic acid, polyglycolic acid, poly(lactic-glycolic acid)) and natural scaffold materials (collagen, chitosan, gelatin, silk fibroin). Each material has its own merits and demerits. Mesenchymal stem cells have a strong self-replicating and multi-directional differentiation ability, which are considered to be relatively ideal seed cells. Based on the characteristics of the components of biological scaffolds and the proliferation and multi-directional differentiation ability of mesenchymal stem cells, it is of great importance for bone defect repair to design and construct ideal biological scaffold materials with better repair function. Construction of a mesenchymal stem cell/3D scaffold complex is still in its infancy. However, the clinical application of biological scaffolds and mesenchymal stem cells in bone tissue engineering is expected to be achieved with the development of nanomaterials, international regenerative medicine and biomimetic science.

BACKGROUND: Loosening of the sterile prosthesis in joint replacement is a simple radiological phenomenon, but a complex immune process. The abrasive particles produced by the implant usually lead to osteolysis, which is known as particle-associated periprosthetic osteolysis. OBJECTIVE: To summarize the characteristics of particle-associated periprosthetic osteolysis in order to provide reference for early identification and treatment, thereby improving the patients' prognosis. METHODS: The first author retrieved PubMed database for the articles addressing particle-associated periprosthetic osteolysis using the English keywords of "wear particles, particle-associated periprosthetic osteolysis".RESULTS AND CONCLUSION: (1) Osteolysis can induce bone resorption, but the relevant clinical, animal and in vitro studies have shown that particle-associated periprosthetic osteolysis involves various biological reactions, not only osteoclasts, and the bioactivity highly depends on the property and quantity. (2) Although total hip arthroplasty has achieved rapid progression, particle-associated periprosthetic osteolysis and aseptic loosening are still the main factors for the life of prosthesis. (3) Biomarkers can be used as simple and objective diagnostic and prognostic criteria for osteolysis after total hip arthroplasty. (4) Further research is needed to identify new biomarkers in periprosthetic osteolysis to develop new treatments to reverse or inhibit the particle-associated biological response.

This study aimed to evaluate the vasorelaxant effect and mechanisms of compound reserpine and triamterene tablets (CRTTs) and its component triamterene on isolated rat thoracic aorta rings. Isolated rat thoracic aorta rings pre-contracted by high potassium or norepinephrine (NE) were used to evaluate the vasodilatory effect of CRTTs and its component triamterene. The mechanisms concerning endothelium, potassium channels and calcium channels were studied through the interventions of several tool drugs. Animal welfare and experimental procedures followed the requirements of the Laboratory Animal Management and Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. The results showed that both CRTTs and triamterene had potent relaxant effect on KCl and NE pre-contracted vessels. Triamterene showed partial endothelium dependency, and N-nitro-L-argininemethyl ester hydrochloride (L-NAME) could influence the relaxant effect, which may be related to the opening of calcium-activated potassium channels. Meanwhile, CRTTs could inhibit intracellular Ca²⁺ release and extracellular Ca²⁺ influx. Overall, CRTTs and its component triamterene have vasorelaxant effects on vessels in vitro, and the vasorelaxant effect of CRTTs may be related to intracellular Ca²⁺ release and extracellular Ca²⁺ influx, while this effect of triamterene may depend on vascular endothelial function and may also be related to the opening of calcium-activated potassium channels.

Collection and rating of evidence,survey of patients' preference and value and economic evaluation of the Practice Guideline for Therapeutic Drug Monitoring of Voriconazole have been finished.The Guideline Consensus Panel reached consensus of the recommendations by 3 rounds Delphi and Grading of Recommendations Assessment,Development and Evaluation grid method.Consensus of 38 recommendations was reached,with a consensus percentage of 50.7％.Twenty seven recommendations were finalized and approved by the Guideline Steering Committee.Draft recommendations were generated.

BACKGROUNDNon-cement femoral stems are recognized in clinical use, but there are still some problems. The aim of this research was to make non-cement femoral stems to be press-fit with the medullary cavity.

METHODSTwenty-four healthy adult mongrel dogs were randomly divided into experimental and control groups. In the right hip joint, an artificial femoral bone replacement surgery was conducted. For the experimental group, the replacement surgery of hydroxyapatite (HA)-coated femoral stems was done, while autogeneous morselized bone was implanted into the medullary cavity. For the control group, morselized bone was not implanted. At postoperative 1, 3, 6 months, a test for interfacial shear characteristics was conducted in the MTS810 Tester. The comparison between the two groups' bone-prostheses in shear strength for their interface from shearing destruction was made. A histological observation to check prosthesis-bone interface contact ratios and bone growth was carried out.

RESULTSFor the experimental group, shear strength was 0.317 MPa in 1 month, 1.447 MPa in 3 months, and 1.621 MPa in 6 months. For the control group, shear strength was 0.195 MPa in 1 month, 1.023 MPa in 3 months, and 1.483 MPa in 6 months. The difference was statistically significant. Stereomicroscope-based observation showed that the number of trabecular bones in the experimental group was larger than that of the control group, and bone growth of the former group was better than that of the latter group. Inverted microscopic observation showed that the binding degree between the prosthesis and trabecular bone of the experimental group was higher than that of the control group. Comparatively, the experimental group's trabecular bone had more stromal cells.

CONCLUSIONSThe morselized bones can effectively improve the biological bonding strength and bone-contact ratios in the short term for the HA-coated femoral stem and accelerate the bonding process. The use of morselized autogenous bones played a good role in bone in-growth of the femoral bone stem surface.

Animals ; Biomechanical Phenomena ; Coated Materials, Biocompatible ; chemistry ; Dogs ; Durapatite ; chemistry ; Female ; Femur ; pathology ; surgery ; Male ; Osseointegration ; Random Allocation ; Shear Strength

Aim To investigate the effects of salvianol-ic acid D ( SalD) on mitochondrial function and bio- synthesis in SH-SY5Y cells after MPP+injury and the possible mechanisms. Methods The cell model was established by MPP+injury in SH-SY5Y cells. The cytotoxicity of MPP+was detected by MTT assay. The effects of SalD on viability of SH-SY5Y cells were ex-amined by MTT and LDH assay. The apoptosis of SH-SY5Y cells was detected by AO/EB assay. The levels of ROS and mitochondrial superoxide were determined using DCFH-DA and MitoSOX probes, respectively. Mitochondrial function was examined by measuring ATP level and mitochondrial membrane potential. The levels of PGC-1α and its downstream regulatory genes NRF1 and TFAM mRNA were detected by qPCR. The protein levels of PGC-1α, NRF1 and TFAM in cells were detected by Western blot and immunofluorescence assays. Results MPP+injury resulted in a significant reduction of cell viability to 51.34%. 0.1, 1, 5 μmol ·L-1SalD and 5 mmol·L-1NAC could reduce MPP+-induced SH-SY5Y cell injury and LDH release. The cell viability increased to 67.98% , 71.79% , 76.91% and 77.55% , respectively. Moreover, SalD could reduce the increase of intracellular ROS and mi-tochondrial superoxide induced by MPP+, decrease mitochondrial membrane potential and improve mito-chondrial function. SalD also significantly increased both the transcription and expression levels of PGC-1α, NRF1 and TFAM. Conclusion SalD could in-hibit MPP+-induced SH-SY5Y cell injury and improve mitochondrial function and mitochondrial biosynthesis.