Objective: The current investigation aimed to determine the appropriate dosage form by comparing solid dispersion and liposome to achieve the purpose of improving the solubility and bioavailability of linarin. Methods: Linarin solid dispersion (LSD) and linarin liposome (LL) were developed via the solvent method and the thin film hydration method respectively. The Transwell chamber model of Caco-2 cells was established to evaluate the absorption of drug. The pharmacokinetics of linarin, LSD and LL in rats after ig administration were carried out by high performance liquid chromatography (HPLC) method. Results: The solubility of LSD and LL was severally 3.29 times and 3.09 times than that of linarin. The permeation coefficients of LSD and LL were greater than 10

Objective:To study the real-world outcome of China FDA-approved Sofosbuvir (SOF)/Velpatasvir (VEL) in Northwest China.Methods:In this multicenter, prospective, real-world cohort study, we recruited patients from 10 sites from Northwest China, who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019. Patients received SOF (400mg)/VEL (100mg) for 12 weeks, and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis. The primary endpoint was sustained virological response at 12-weeks post-treatment (SVR12) and safety. The secondary endpoint was the change of liver function after the achievement of SVR12.Results:Totally, 143 patients were enrolled in the study, four patients were lost to follow-up and one died during the follow-up, 138 patients were included in per-protocol analysis. Of the 138 patients, the mean age 53 years, 53.6% male, 94.2% Han nationality, 53.6% liver cirrhosis, 10.1% HBsAg +, 6.5% renal dysfunction, 5.1% treatment-experienced, and 16.7% patients received ribavirin treatment. The genotype distribution was as follows: 35.5% GT1, 42.8% GT2, 15.9% GT3, and 5.8% un-typed. The SVR12 rate was 96.5% (138/143, 95% CI: 93.5%-99.6%) for intention-to-treat analysis, and in per-protocol analysis, all 138 patients obtained SVR12 (100%). Compared with baseline, the serum total bilirubin, ALT and AFP levels decreased (all P < 0.05), as well as increased ALB and platelet count (all P < 0.001) at post-treatment 12-weeks. Overall adverse events (AEs) rate is 29.0%, and the most common AEs were anemia (14.5%) and fatigue (8.0%). Severe side effects (edema and fatigue) occurred in 2 patients, one of whom needed a short-term interruption of treatment due to fatigue. Conclusion:In this real-world cohort study, 12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates (96.5%-100% overall) with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis, and led to improvement of liver function.

Assisted reproductive technology (ART), as an important means of procreation, has been increasingly applied to clinical practice. Morphological evaluation and genetic screening before embryo implantation is an important part of modern ART and an essential means to improve embryo implantation rate and clinical pregnancy rate. The safety of existing preimplantation genetic screening methods has been questioned due to their needs for embryo biopsies. How to achieve non-invasive preimplantation screening has become a research hotspot at the present stage. This paper mainly discusses some methods or technologies with clinical value in recent years, hoping to provide references for the clinical application of non-invasive screening.

Assisted reproductive technology (ART), as an important means of procreation, has been increasingly applied to clinical practice. Morphological evaluation and genetic screening before embryo implantation is an important part of modern ART and an essential means to improve embryo implantation rate and clinical pregnancy rate. The safety of existing preimplantation genetic screening methods has been questioned due to their needs for embryo biopsies. How to achieve non-invasive preimplantation screening has become a research hotspot at the present stage. This paper mainly discusses some methods or technologies with clinical value in recent years, hoping to provide references for the clinical application of non-invasive screening.

Objective To analyze the clinical effects of thrombolytic therapy in patients with ischemic in-hos-pital stroke (IHS). Methods The clinical data were collected from patients with ischemic IHS in the last five years. The patients were divided into thrombolysis group and non-thrombolysis group, according to the use of recombinant tissue plasminogen activator (r-tPA) treatment. The clinical outcomes were measured by the modified Rankin scale (mRS) at discharge. Results There were a total of 121 patients in this study. There were 6 patients in thrombolysis group and 115 patients in the non-thrombolysis group, respectively. Six patients (100%) in the thrombolysis group achieved favor-able outcomes (mRS 0~2) at discharge whereas only 42 patients (36.5%) in the non-thrombolysis group achieved fa-vourable outcomes. The rate of favorable outcomes was significantly higher in the thrombolysis group than in the non-thrombolysis group (P<0.05). Conclusions R-tPA thrombolytic therapy can improve the prognosis of patients with ischemic IHS.

After ischemic stroke, secondary damages such as neuron loss, gliosis, and axonal degeneration occur in the nonischemic remote brain regions that have synaptic connections with the primary infarction site.These secondary damages in the remote brain regions may affect the recovery of neurological function.Several advanced neuroimaging techniques have been used to detect these secondary damages.This article reviews the research progress in this field.

BACKGROUND: Alginic acid has a relatively mild gel condition and good biocompatibility, and it has been widely used in bio-tissue engineering.OBJECTIVE: To construct bone tissue engineering scaffolds using alginate gel composite bone xenograft approach, and to observe the cell biological properties and in vivo osteogenic potential in scaffolds.METHODS: The bone marrow was harvested from two 2-week-old New Zealand rabbits, 1 ×10~(-8)mol/L recombinant human bone morphogenetic protein-2 was used to induce bone marrow mesenchymal stem cells. The induced bone marrow mesenchymal stem cells at the second generation were incubated into 1% sodium alginate gel, after cultured for 4 days, the cell morphology in gel was observed by hematoxylin-eosin staining. Bone marrow mesenchymal stem cells at the second generation were divided into simple DMEM gel group and DMEM containing 1% sodium alginate gel group, followed by a culture of 7 days. Then bone morphogenic protein-2 immunohistochemical staining was performed. A total of 24 nude mice were randomly divided into two groups, both sides of the thigh muscle pockets were implanted with bone marrow-derived mesenchymal stem cells/alginate gel/bovine cancellous bone complex as an experimental group, with bone marrow-derived mesenchymal stem cells/bovine cancellous bone as a control group. At 2 and 4 weeks post-operation, the osteogenesis in the composite was observed by histological examination, the percentage area of new bone or cartilage was determined using image analysis system.RESULTS AND CONCLUSION: The bone marrow-derived mesenchymal stern cells in the sodium alginate gel exhibited a well-stacked morphology, they suspended in a gel, showing cell division and mitosis phase. In the simple DMEM gel group and DMEM gel containing 1% sodium alginate group, the immunohistochemical results showed that, cell division and proliferation were normal, with prominence at a variety of forms, large nucleus, and clear nucleolus. The bone morphogenetic protein-2 expression had no significant difference between the simple DMEM gel group and DMEM gel containing 1% sodium alginate group (P>0.05).Scanning electron microscopy revealed that, the alginate gel evenly composited in bovine cancellous bone micropores, cell grew at different planes. Animal experiments showed that there were significant differences regarding the percentage of new bone or cartilage area between the experimental group and control group at 2 and 4 weeks postoperation (P< 0.05). It is indicated that constructing bone tissue engineering scaffolds by using alginate gel/bovine cancellous bone, complies with the ultra-structural principle of tissue engineering scaffolds, can maximize the cell loads, achieve good bio-performance, without adverse affects on the proliferation, osteogenic phenotype and related biological properties of bone marrow-derived mesenchymal stem calls, the in vivo osteogenic efficiency was high.

Under laboratory condition, the compound materials of Poly (DL-lactic-co-glycolic acid)/Tricalcium phosphate [PLGA/TCP(L), with component ratio of 7:3] were fabricated by combining the thermally induced phase separation (TIPS) with solvent-casting particulate-leaching (SCPL) approach. On the other hand, rapid prototyping (RP) technique manufactured PLGA/TCP scaffolds [PLGA/TCP(RP)] were obtained. These two kinds of carriers were coated with collagen type I (Col I). The extracted bovine bone morphogenetic protein (bBMP) was loaded into carriers to establish biomimetic synthetic bones. PLGA/TCP(L) scaffolds, demineralized bone matrices (DBM) of bovine cancellous bone, PLGA/TCP(L) scaffolds, biomimetic synthetic bones and OsteoSet bone graft substitutes were investigated. Scanning electron microscopy revealed that the microarchitecture of PLGA/TCP(RP) scaffolds was much better than that of PLGA/TCP(L) scaffolds. The diameter of macropore of PLGA/TCP(RP) scaffold was 350 microm. The porosities of PLGA/ TCP(L) scaffolds, DBM, PLGA/TCP(RP) scaffolds and OsteoSet bone graft substitutes were 21.5%, 70.4%, 58.6% and 0%, respectively (P<0.01). Modification of PLGA/TCP scaffolds with collagen type I [PLGA/TCP(L)-Col I and PLGA/TCP(RP)-Col I] essentially increased the affinity of the carriers to bBMP. Among these synthetic materials, PLGA/TCP(RP)-Col I-bBMP composite is promising as a novel bone graft substitute due to its advanced fabrication technique, good tri-dimensional microarchitecture and ideal components.
Biocompatible Materials ; chemistry ; Bone Morphogenetic Proteins ; chemistry ; Bone Substitutes ; chemistry ; Calcium Phosphates ; chemistry ; Humans ; Lactic Acid ; chemistry ; Microscopy, Electron, Scanning ; Polyglycolic Acid ; chemistry ; Porosity ; Surface Properties ; Tissue Engineering ; methods

BACKGROUND:The structure of tissue engineering carrier affects the bio-action of cells greatly.OBJECTIVE: To investigate the biological characteristics of bone marrow stem cells (MSCs) in different concentrations of alginate combined with de-antigen bone xenograft (DBX).DESIGN: Observational trial.SETTING: PLA Institute of Trauma and Orthopedics, the Fourth Military Medical University of Chinese PLA.MATERIALS: Alginate, calcium chloride, MSCs, bone xenograft.METHODS: Bovine cancellous bone was out into cubes, which were degreased, deproteinized and then lyophilized.Cubes in pore size within 300-500 μm were selected for use after ethylene oxide sterilization. The purified sodium alginate was dissolved in DMEM cell culture medium of concentrations as different as 0.5%, 2%, 8% and 16%; 1×1012 L-1 induced MSCs were blended with isopyknic alginate-DMEM and compounded with DBX at a status of 0.5 Mpa negative pressure for 5 minutes in order to make a cell suspension fully fill into the pores of the cancellous bone. Then alginate was crosslinked with 50 g/L calcium gluconic acid for 30 seconds. The complex was put into a CO2 incubator and cultured for 4 days. The gel compound and cell growth in the pores of the complex were grossly observed with an inverted microscope. Status of cell growth in the complex with different concentrations of alginate was observed with scanning electron microscopeMAIN OUTCOME MEASURES: Compound status of alginate and bone xenograft, cell growth status and matrix secretion in compound carries.RESULTS: When the concentration of alginate was 0.25% or 1%, alginate was equally combined in DBX, while that of 4% and 8% only combined on the surface of cancellous bone. After in vitro cultured for 4 days, alginate of 0.25% were broken off from DBX surface. But alginate of 1% was equally combined with DBX pores with cells secreting well in alginate. Development of cells in alginate of 4% was restricted and no cells were seen in alginate of 8%.CONCLUSION: Alginate of 1% is suitable for constructing the carrier of bone tissue engineering with bone xenograft.

BACKGROUND: For xenogeneic bone transplantation, immune rejection is the major problem that affects the prognosis. However, the understanding about the expression and regulation of the immune factors in heterogenic bone transplantation is limited. Interleukin-1 (IL-1), interleukin-6 (IL-6)and tumor necrosis factor alpha (TNF-α) are important immune factors, and are closely related with post-transplantation rejection.OBJECTIVE: To observe the regional expressions of mRNA and protein of IL-1α, IL-6 and TNF-α in xenogeneic bone transplantation, and to in vestigate the effect of transforming growth factor (TGF)-β on these immune factors.DESIGN: A randomized controlled experiment. SETTING: The Orthopaedic Institute of Xijing Hospital of the Fourth Military Medical University of Chinese PLA MATERIALS: Totally 72 male Balb/c mice, with a body mass of 20 to 25 g, were randomly divided into 3 groups: combined bovine cancellous bone (bCB) granule group (Group A), simple bCB granule group (Group B) and blank control group (Group C) with 24 mice in each group.INTERVENTIONS: This experiment was conducted at the Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical Univessity of Chinese PLA from June 2003 to June 2004. In Group A, one bCB combined TGF-β was implanted into the muscles of left thigh of each mouse. In Group B, one bCB alone was implanted, and in Group C, no bCB was implanted. The number of proliferation of cells in bone implantation area or adjacent tissues of the operated area was observed at postoperative 4, 7, 14 and 21 days; and the regional expressions of several immune factors in im plants were detected with in situ hybridization and immunocytochemistry methods.MAIN OUTCOME MEASURES: Histological observation and detection of regional cellular density of the implants of the mice in each group; the regional expressions of mRNA and protein of IL-1α,IL-6 and TNF-α in the implants RESULTS: ①) Histological observation and detection of regional cellular density of the implants of the mice in each group: on day 7, the cellular density of the proliferated tissues was significantly higher in the Group A than in the Group B [(470.63±132.89), (311.46±93.69)/field,P ＜ 0.01];But on days 14 and 21, there was no significant difference. ②The regional expressions of mRNA and protein of IL-lα, IL-6 and TNF-α of the im plants of the mice in each group. On days 7 and 14 after xenografts were implanted, the regional expressions of IL-1α, IL-6 was respectively lower the xenografts combined with TGF-βthan in the simple xenogeneic bone (day 7: IL-1α 42.55±9.65 vs 67.95±17.82,IL-6 48.26±11.17 vs 77.21±15,16;day 14: IL-1α mRNA 84.77 ±7.42 vs 112.94±7.02,78.1 ±17.22 vs 121.18±15.44,P ＜ 0.01) ,but for the TNF-α, there was no significant difference (P ＞ 0.05).CONCLUSION: In the region of bone xenograft, a variety of cells express mRNAs and proteins of IL-1α, IL-6 and TNF-α, and their expressions are regulated by TGF-β. It may imply a kind of regulation of the immunity of bone xenograft by TGF-β.