The low aqueous solubility is the main reason that for most pharmacological active ingredients are challengeable to develop into oral solid formulation. Polymeric amorphous solid dispersion(PASD) can greatly improve the apparent solubility and dissolution rate of poorly soluble drugs, has become a common technology to improve the oral bioavailability of poorly soluble drugs. However, due to the amorphous form of the drug at a high surface free energy in PASD, crystallization would occur during storage and dissolution, thereby losing its formulation advantages. The review attempts to provide a structural development approach of PASD products from the aspects of formulation and technology, in order to guide the development of stable and commercially viable PASD formulations. And the trend analysis of marketed products and patents of PASD will be discussed to understand the prospects of PASD's application in improving the bioavailability of poorly soluble oral solid formulations.

The most effective sequence of small interfering RNA (siRNA) silencing STAT3 of psoriatic keratinocytes (KCs) was screened out,and the effects of the most effective siRNA combined with ultrasonic irradiation and SonoVue microbubbles on the expression of STAT3 of KCs and the dose-and time-response were investigated.Three chemically-synthetic siRNAs targeting STAT3 carried by Lipofectamine 3000 were transfected into KCs,and the effects on STAT3 expression were detected,then the most effective siRNA was selected for the subsequent experiments.The negative controls of siRNA (siRNA-NC) labeled with Cy3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles were transfected into KCs,then the optimal parameters of ultrasonic irradiation were determined.The most effective siRNA carried by Lipofectamine 3000 combined with ultrasonic irradiation at the optimal parameters and SonoVue microbubbles was transfected into KCs,and the dose-and time-response of RNA interference was determined.The effect of RNA interference by the most effective siRNA at the optimal time and dose carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group) was compared with that only carried by Lipofectamine 3000 (L group).The results showed that siRNA-3 achieved the highest silencing efficacy.0.5 W/cm2 and 30 s were selected as the parameters of ultrasonic irradiation.The siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue mierobubbles could effectively knock down the STAT3 expression at mRNA and protein levels in dose-and time-dependent manners determined at 100 nmol/L with maximum downregulation on mRNA at 48 h,and on protein at 72 h after transfection.The LUS group achieved the highest silencing efficacy.It was concluded that siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles could effectively knock down the STAT3 expression in psoriatic KCs,and the optimized transfection condition and the sequence of siRNA-3 could serve for further research on gene therapy of psoriasis.

Cleistocalycis Operculati Cortex is the dry bark of Cleistocalyx operculatus. It is the raw material of Compound Hibiscuse which is external sterilization antipruritic drugs. The quality standard of Cleistocalycis Operculati Cortex in Guangdong Province "standard for the traditional Chinese medicine" (second volumes) only contains TLC identification. It is unable to effectively monitor and control the quality of Cleistocalycis Operculati Cortex. A reversed-phase HPLC method was established for the determination of 3, 3'-O-dimethylellagic acid from Cleistocalycis Operculati Cortex and the content was calculated by external standard method for the first time. Under the selected chromatographic conditions, the target components between peaks to achieve effective separation. 3,3'-O- dimethylellagic acid standard solution at the concentration of 1.00 - 25.0 mg x L(-1) showed a good linear relationship. The standard curve was Y = 77.33X + 7.904, r = 0.999 5. The average recovery was 101.0%, RSD was 1.3%. The HPLC method for the determination of 3,3'-O-dimethylellagic acid in Cleistocalycis Operculati Cortex is accurate and reliable. It can provide a strong technical support for monitoring the quality of Cleistocalycis Operculati Cortex.
Chromatography, High Pressure Liquid ; methods ; Chromatography, Reverse-Phase ; methods ; Drugs, Chinese Herbal ; analysis ; Plant Bark ; chemistry ; Syzygium ; chemistry

Objective To investigate the effect of brain-derived neurotrophic factor (BDNF) gene modified neural stem cells (NSCs)transplantation on cerebral ischemic injury in rats.Methods NSCs from newborn rat hippocampus were isolated,cultured in a medium containing fibroblast factor (FGF) in vitro. Their proliferation and differentiation were detected by immunohistochemistry.Virus vectors pLXSN-BDNF were built and BDNF were transfected into NSCs.Biological activity were detected to obtained engineering stem cells of BDNF protein with secretary activity.Middle cerebral artery occlusion (MCAO) models were made and transplanted with NSCs-BDNF by stereotaxic technique.The effect of transplantation on MCAO models was evaluated histologically and behaviorally.Results Statistical analysis showed that the behavioral performance of the animals improved after transplantation (Longa mark being 1.343?0.293 four weeks after stem cell transplantation).The number of hippocampal dentate gyrus neurons increased to 87.5%?6.6% , four weeks after stem cell transplantation on Nissle stained hippocampal sections,which was significantly different from that of controls.Positively BrdU stained neural stem cells revealed by immunohistochemistry in the cultured cells and in the transplanted brain sections,indicated that the engineering cells transplanted had survived in the host brain and began to proliferate.Conclusion Transplantation of BDNF genetically modified NSCs can effectively promote the recovery from cerebral ischemic injury.

Cutaneous Fistula ; Digestive System Abnormalities ; therapy ; Endoscopy, Gastrointestinal ; methods ; Female ; Humans ; Infant ; Treatment Outcome

Objective To investigate the effects of repeated neonatal administration of dizocipline maleate (MK-801), the N-methyl-D-aspartate (NMDA) receptor antagonist, on the expression of NMDA receptor subunits NMDAR 1 (NR1), NMDAR2A (NR2A), NMDAR2B (NR2B) and the protein levels of nerve growth factor (NGF) in neonatal rats. Methods Neonatal Sprague-Dawley (SD) rats were randomly divided into research group and control group, with 15 ani-mals in each group. Rats were administrated subcutaneously with MK-801 or normal saline from postnatal day (PND) 5 to PND14 (0.25 mg/kg, twice a day). The expression levels of NR1, NR2A, NR2B and NGF were examined on PND15, PND42 and PND70 in the prefrontal cortex and hippocampus. Results At PND15 (neonatal period), there were no signifi-cant differences in the expression levels of NR1, NR2A, NR2B and NGF in the prefrontal cortex and hippocampus be- tween the two groups (P>0.05). At PND42 (adolescence), NGF protein levels in the prefrontal cortex was significantly low-er in research group than in control group [(56.19±37.87) vs. (152.54±53.92), P<0.01]. At PND70 (adulthood), the expres-sion of NR1, NR2A in the hippocampus was significantly higher in research group than in control group [NR1:(149.55%± 27.00%) vs. (100.00%±32.08%);NR2A:(171.54%±19.85%) vs. (100.00%±51.04%). P<0.05]. Conclusion Neonatal re-peated treatment of MK-801 increases the expression of NMDA receptor subunits NR1, NR2A in the hippocampus in adulthood while decreases the expression of NGF in the prefrontal cortex in adolescence, suggesting that neonatal block-ade of the NMDA receptor may influence the growth and development of the nervous system.

AlM: To investigate expressions of matrix metalloproteinase-2 ( MMP-2 ) and extracellular matrix metalloproteinase inducer ( EMMPRlN) in retinoblastoma (Rb) and the relationships between MMP-2, EMMPRlN and tumor development.METHODS:lmmunohistochemical technique was used to detect expressions of MMP-2 and EMMPRlN in 39 cases of paraffin embedded Rb samples. Quantitative analysis of expressions of MMP-2 and EMMPRlN were assessed by measuring the mean gray scale of Rb tissue with LElCA lM50 Color Pathologic Analysis System. The differences of expressions of MMP-2 and EMMPRlN in each clinical and pathological stage were statistically analyzed, and the same step was also undertaken to study the relationship between Rb with MMP-2 positive expression and that with EMMPRlN positive expression.RESULTS:The positive expression rate of MMP-2 was 90% (Gray value: 109. 64 ± 14. 52; 35/39), and that of EMMPRlN was 85% (Gray value:108. 01±13. 60;33/39). The expressions of MMP - 2 and EMMPRlN were significantly higher in tumors of glaucomatous stage (Gray value:108. 21±11. 47 and 107. 56±14. 32) than those in intraocular stage ( Gray value: 121. 13 ± 11. 32 and 119. 34 ± 12. 66; P<0. 01 and P<0. 05). And the same conclusion can be concluded between those in extraocular stage (Gray value: 91. 03 ± 11. 71 and 92. 26 ± 12. 93) with those in glaucomatous stage (P<0. 01 and P<0. 05). The expressions of MMP-2 and EMMPRlN were significantly higher in tumors with optic nerve invasion (Gray value:103. 89±13. 39 and 105. 23±14. 00) than those without optic nerve invasion ( Gray value: 118. 39 ± 15. 11 and 117. 53±16. 13) (P<0. 01 and P<0. 05).CONCLUSlON:The positive expression levels of MMP-2 and EMMPRlN may correlate with tumor infiltration and metastasis.

To develop a LC-MS/MS method for the determination of five kinds of trace ginkgolic acids in diterpene ginkgolides meglumine injection materials, the column was Agilent ZORBAX Eclipse plus C18 (3.0 mm x 50 mm, 1.8 µm), and the mobile phase consisted of methanol-water (containing 0.2% formic acid) (95:5) at a flow rate of 0.5 mL · min(-1). The multiple reaction ion monitoring (MRM) with an ESI interface in the negative ion mode was selected. The results showed that the linear ranges of five kinds of ginkgolic acids were in the range of 0.2-36.0 µg · L(-1) (r ≥ 0.999 5). The lowest limit of quantification (LOQ) of ginkgo acid C13: 0, C15:1, C17:2, C15:0 and C17:1 were 0.18, 0.18, 0.21, 0.10 and 0.20 µg · L(-1), respectively. The average recovery was between 73.28% and 87.56%, and the average content of total ginkgolic acids in three batches of samples was in the range of 0.023-0.028 µg · g(-1), which was much lower than 2 µg · g(-1) prescribed in drug registration standards. This method is simple and rapid with high sensitivity, which can be used for the determination of five kinds of trace ginkgolic acids in diterpene ginkgolides meglumine injection materials.
Chromatography, Liquid ; methods ; Ginkgolides ; analysis ; Injections ; Limit of Detection ; Salicylates ; analysis ; Tandem Mass Spectrometry ; methods

Objective To observe the effect of acupuncture plus rehabilitation in treating deglutition disorders due to cerebral stroke and its effect on each link of the neural pathway of deglutition function. Method By adopting the prospective randomized controlled method, ninety-nine patients with deglutition disorders after cerebral stroke were recruited and divided into an acupuncture-rehabilitation group, a pharyngeal acupuncture group, and a control group, respectively 33 cases, 34 cases, and 32 cases in each group. The acupuncture-rehabilitation group was intervened by acupuncture respectively at scalp, pharyngeal, and the root of tongue plus basic treatment, the pharyngeal acupuncture group was by acupuncture at the deglutition point (Extra) plus basic treatment, while the control group was by the basic treatment alone, once a day, 4 weeks in total. The Functional Oral Intake Scale (FOIS) and Clinical Nursing Swallowing Assessment Tool (CNSAT) were evaluated and statistically analyzed before and after intervention. Result The component scores of CNSAT were significantly improved after intervention in the acupuncture-rehabilitation group (P<0.01); the component scores of CNSAT were significantly changed after intervention in the pharyngeal acupuncture group (P<0.05);the CNSAT component scores in the acupuncture-rehabilitation group were significantly different from that in the pharyngeal acupuncture group and control group after intervention (P<0.01); the CNSAT component scores in the pharyngeal acupuncture group were significantly different from that in the control group after intervention (P<0.05). The FOIS scores were enhanced in the three groups after treatment; the FOIS score was significantly changed in the acupuncture-rehabilitation group after intervention (P<0.01);the FOIS score was markedly changed in the pharyngeal acupuncture group after intervention (P<0.05);the FOIS scores in the acupuncture-rehabilitation group and pharyngeal acupuncture group were both significantly higher than that in the control group (P<0.01,P<0.05). Conclusion The scalp-pharyngeal-root of tongue sequential-acupuncture plus rehabilitation can effectively mitigate the deglutition problems after cerebral stroke, improve the food-intake ability of the patients, and reduce the risk of mistake inhalation.

Cerebrovascular disease has become the first cause of death in China, which brings heavy social economy burden and psychological pressure to the patients and their families. Recent years have witnessed rapid development in cerebrovascular disease research, which promotes the rapid development of its prevention and treatment. This review summarized several focuses in studies of cerebrovascular diseases, including focuses of basic research, diagnoses and therapies of acute ischemic stroke and endovascular treatments, cerebral hemorrhage, prevention and rehabilitation of cerebral stroke, evidence-based medicine, translational medicine and precision medicine, hoping to provide insights for all those who involved in the field.