To prepare the oral self-microemulsifying drug delivery system (SMEDDS) of GBE50, balance solubility method was used to screen emulsifier and assistant emulsifier; a pseudo-tamary phase diagram was used to prepare microemulsion; and orthogonal design was used to optimize formulation. Self-microemulsifying efficiency, dissolution, stability and pharmacokinetics of the preparation were studied. As a result, GBE50-SMEDDS of IPM, Cremophor EL, 1,2-propanediol and GBE50 could be self emulsified to form stable microemulsion with particle diameter between 20 and 50 nm when emulsifying with water. Its self-microemulsifying efficiency and dissolution are quick with good stability and it has a higher bioavailability than market existing agents Xingling particles. GBE50-SMEDDS is stable and effective.
Biological Availability ; Drug Delivery Systems ; methods ; Drugs, Chinese Herbal ; administration & dosage ; chemical synthesis ; pharmacokinetics ; Ginkgolides ; administration & dosage ; chemical synthesis ; pharmacokinetics ; Technology, Pharmaceutical ; methods

Objective To assess the accuracy of puncture guided by intelligent positioning (IP) system using magnetic navigation.Methods Five prepared targeted models at three certain depth (<50 mm, samll depth;50-100 mm,medium depth;>100 mm,large depth) underwent puncture guided by intelligent positioning system using IP and conventional ultrasound (US),respectively.Puncture errors,the number of attempt and spent time were recorded and compared .Results For the targets at small,medium and large depth,the errors of IP was (1.88 ±1.18),(1.56 ±0.56) and (3.99 ±1.10) cm,and the errors of conventional US was (4.52 ±2.23),(4.49 ±1.73) and (3.93 ±2.19) cm respectively.The errors of IP were significantly less than those of conventional US at small(t=-2.345,P=0.047) and medium(t=-3.608,P=0.007) depth,but there was no statistically significant difference at large depth (t=0.058,P=0.955). In the IP group,there were statistically significant differences for puncture errors between the small and large depth,as well as between medium and large depth ( F =8.923,P =0.010).There was no statistically significant difference for the errors of IP between the small and medium depth (t=-1.927,P=0.501).For the targets at small,medium and large depth,each puncture was performed in single attempt when guided by IP and in 2,1 and 2 attempt when guided by conventional US .At small and large depth,the numbers of attempt of IP were significantly less than those of conventional US (U=-2.372,P=0.018;U=-2.39, P=0.032).Whereas at medium depth,there was no significant difference (U=-1.000,P=0.690).For the targets at small,medium and large depth,each puncture spent (21.20 ±2.39)s, (27.00 ±4.00)s and (31.80 ±3.83)s when guided by IP,and(45.20 ±9.68),(26.80 ±4.21) and (54.60 ±13.48)s when guided by conventional US.The spent time of IP was less than that with conventional US for small and large depth targets(t =-5.383, P =0.001;t =-3.637, P =0.007).Whereas no statistically significant difference was found for the medium depth target (t=0.077,P=0.916).Conclusion In comparison with conventional US,IP system guided puncture is more accurate and the number of attempt and spent time is less .

Objective To investigate the imaging features of active Crohn′s disease on conventional ultrasound and contrast-enhanced ultrasound (CEUS). Methods The imaging features of 20 patients with an established diagnosis of Crohn′s disease on transabdominal high-frequency ultrasound and contrast-enhanced ultrasound in Shanghai Tenth People′s Hospital from August 2011 to December 2012 were studied retrospectively. Contrast-specific imaging modes were performed and the ultrasound contrast agent was SonoVue. The thickness of inner, outer and all layers of intestinal walls in the lesion area were observed;the ratio between inner and outer bowel wall thickness was calculated;Limberg classiifcation was determined by Power-Doppler results. Likewise, contrast-enhanced ultrasound was used to evaluate the degree and area of bowel wall enhancement, as well as the changes over time. Variance analysis was applied to compare intestinal wall thickness, arrive time of contrast agent, time to peak and washing time of patients with Crohn′s disease from different Limberg groups, and further comparison between groups were anlysed with LSD-t test. Results The intestinal wall thickness of all 20 patients was larger than 4 mm, while the mean thickness of intestinal walls was (8.8±0.4) mm (range 5.5-12.0 mm);the ratio between inner and outer wall thickness was greater than 1.0. Limberg classiifcation wasⅡin 2 patients,Ⅲin 8 patients andⅣin 10 patients. There were two enhancement patterns shown on contrast-enhanced ultrasound:Pattern 1 in 13 (13/20, 65.0%) patients showing simultaneous enhancement in both inner and outer intestinal walls at the same time. Pattern 2 in 7 (7/20, 35.0%) patients showing outward enhancement from inner to outer wall with a predominance of inner wall. The wall thicknesses of patients with Crohn′s disease from Limberg Ⅱgroup, Limberg Ⅲgroup and Limberg Ⅳgroup were (6.6±0.1), (7.5±0.4) and (10.2±0.4) mm respectively. The thicknesses of inner bowel walls were (3.6±0.6), (5.0±0.2) and (7.3±0.3) mm respectively. CEUS time to peak was (30.5±2.1), (26.9±2.4) and (21.0±1.6) s respectively. The wash-in time of the contrast agent was (18.0±5.7), (10.6±1.0) and (8.7±1.2) s respectively. As the Limberg level increased, the thickness of the entire and inner bowel wall both increased, while CEUS time to peak and wash-in time of the contrast agent became longer. These difference was statistically significant. In addition, the ratio between inner and outter wall thickness also increased as the Limberg level increased, however, the difference was statistically insigniifcant. Likewise, the outer bowel wall thickness and the arrival time of the contrast agent in patients with Crohn′s diseases from different Limberg level groups showed no statistical significance. Conclusions The patients with active Crohn′s disease always showed thickened bowel walls, higher Limberg level and complete or partial enhancement of bowel wall on CEUS. There were some correlations between the above-mentioned ifndings.

OBJECTIVETo investigate the effect of the combination therapy of biofeedback with electrical stimulation on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) through clinical trials.

METHODSA total of 140 cases of diagnosed CP/CPPS were randomly divided into a control group (n = 20), a biofeedback group (BF, n = 40), an electrical stimulation group (ES, n = 40), and a biofeedback plus electrical stimulation group (BF + ES, n = 40). The latter three groups were treated by corresponding methods 5 times a week for 2 weeks, while the controls left untreated. After the treatment, all the patients were followed up for 30 days. The NIH chronic prostatitis symptom index (NIH-CPSI) scores and the results of uroflowmetry were obtained and compared before and after the treatment.

RESULTSCompared with the control group, the scores on pain, urinary symptoms and quality of life (QOL) and the total NIH-CPSI scores were obviously decreased (P < 0.05), and the maximum flow rate (MFR) markedly improved (P < 0.05) in the BF, ES and BF + ES groups after the treatment, with significant differences between the former two and the latter one (P < 0.05), but not between the BF and ES groups (P > 0.05), nor in the control group before and after the treatment (P > 0.05).

CONCLUSIONThe combination therapy of biofeedback with electrical stimulation has a synergistic effect on CP/CPPS by alleviating pain and urinary symptoms, improving QOL and elevating MFR.

Adolescent ; Adult ; Biofeedback, Psychology ; Chronic Disease ; Electric Stimulation ; Humans ; Male ; Middle Aged ; Pelvic Pain ; therapy ; Prostatitis ; therapy ; Syndrome ; Young Adult

BACKGROUND: Posterior pedicle screw fixation of lower cervical spine has many advantages. However, because of the special anatomy of pedicle, the technical requirements of nailing placement are high and it is also a challenge to surgeons. The application of three-dimensional (3D) printing technology can help to complete screw placement, and has certain advantages. OBJECTIVE: To introduce the method of 3D printing personalized navigation template assisted posterior lower cervical pedicle screw fixation and evaluate its clinical application value. METHODS: Totally 20 patients with lower cervical spine pedicle screw internal fixation who were treated from June 2015 to December 2016 in Affiliated Hospital of Yan'an University were retrospectively analyzed. Before the surgery, the patient's lower cervical spine CT data was introduced into the relevant software and the 3D printing personalized navigation template assisted nailing pedicle screw was designed. The number of screws inserted was recorded. After the operation, CT scan was used to calculate the accuracy rate of screw placement. Preoperative and postoperative cervical spine Visual Analogue Scale score and spinal function score of Japanese Orthopedic Association were used to evaluate the clinical effect of cervical nerve. RESULTS AND CONCLUSION: (1) All patients were followed up for 3 months postoperatively. (2) 3D printing personalized navigation template assisted 132 pedicle screws. The precise insertion rate was 94.7%. Among them, 125 screws were at grade 0 (94.7%, 125/132), 3 screws grade 1 (2.3%, 3/132), 4 screws grade 2 (3.0%, 4/132), no screw grade 3. (3) At postoperative 1 and 3 months, the neck shoulder Visual Analogue Scale score and spinal function score of Japanese Orthopedic Association of the patients were significantly improved (P < 0.05), but there was no significant difference (P > 0.05), compared with those at preoperative. (4) In summary, 3D printing personalized navigation template assisted cervical pedicle screw placement had the high insertion rate and satisfactory clinical efficacy.

BACKGROUNDThe neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil (FA, COX inhibitor) and its therapeutic time window in a model of transient middle cerebral artery occlusion (MCAO) in rats.

METHODSForty-eight male SD rats were randomly assigned into six groups (n = 8 in each group); three FA groups, vehicle, sham and ischemia/reperfusion (I/R) groups. Three doses of FA (5, 10 or 20 mg/kg, intravenous infusion) were administered just after cerebral ischemia/reperfusion (I/R). The degree of neurological outcome was measured by the neurologic deficit score (NDS) at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage (MBIVP) was determined with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 hours after I/R. In three other groups (n = 8 in each group), the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R.

RESULTSThe three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12 - 24 hours after ischemia reperfusion.

CONCLUSIONCOX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12 - 24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.

Animals ; Cyclooxygenase Inhibitors ; administration & dosage ; pharmacology ; Disease Models, Animal ; Flurbiprofen ; administration & dosage ; analogs & derivatives ; pharmacology ; Infusions, Intravenous ; Ischemic Attack, Transient ; chemically induced ; drug therapy ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Time Factors

OBJECTIVETo investigate the effects of neuropeptide Y (NPY) Y1 receptor antagonist PD160170 in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and accelerating healing of femoral defect in rats.

METHODSThe third generation of rat BMSCs were treated with PBS (control) or 10, 10, or 10 mol/L NPY Y1 receptor antagonist PD160170. After 7 and 14 days of treatment, the cells were examined for osteogenic differentiation with alkaline phosphatase (ALP) and alizarin red staining. At 7 and 21 days of treatment, the mRNA and protein expressions of collagen type I (COLI), osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) in the cells were detected using q-PCR and Westem Blotting. In a male SD rat model (body weight 300∓20 g) of bilateral femoral condyle defects (2.5 mm in diameter), the effect of daily local injection of 0.2 mL PD160170 (10 and 10 mol/L, for 28 consecutive days) in promoting bone defect repair was evaluated with micro-CT scans.

RESULTSALP and alizarin red staining showed that the BMSCs treated with PD160170, at the optimal concentration of 10 mol/L, contained more intracellular cytoplasmic brown particles and mineralized nodules in extracellular matrix than PBS-treated cells. PD160170 (10 mol/L) significantly up-regulated the mRNA and protein expressions of COLI at day 7 and those of OCN and Runx2 at day 21 (P<0.05). In the rat models of femoral bone defect, the volume/tissue volume ratio, bone mineral density and the number of bone trabeculae were significantly greater in 10 mol/L PD160170 group than in the control group (P<0.05), but the bone trabecular thickness (P=0.07) and bone volume (P=0.35) were similar between the two groups.

CONCLUSIONNPY Y1 receptor antagonist PD160170 can promote osteogenic differentiation of BMSCs and healing of femoral defects in rats, suggesting the potential of therapeutic strategies targeting NPY Y1 receptor signaling in the prevention and treatment of bone fracture and osteoporosis.

OBJECTIVETo clone and express nucleocapsid (N) protein of the severe acute respiratory syndrome (SARS)-associated coronavirus, and to evaluate its antigenicity and application value in the development of serological diagnostic test for SARS.

METHODSSARS-associated coronavirus N protein gene was amplified from its genomic RNA by reverse transcript nested polymerase chain reaction (RT-nested-PCR) and cloned into pBAD/Thio-TOPO prokaryotic expression vector. The recombinant N fusion protein was expressed and purified, and its antigenicity and specificity was analyzed by Western Blot, to establish the recombinant N protein-based ELISA for detection of IgG antibodies to SARS-associated coronavirus, and SARS-associated coronavirus lysates-based ELISA was compared parallelly.

RESULTSThe recombinant expression vector produced high level of the N fusion protein after induction, and that protein was purified successfully by affinity chromatography and displayed higher antigenicity and specificity as compared with whole virus lysates.

CONCLUSIONThe recombinant SARS-associated coronavirus N protein possessed better antigenicity and specificity and could be employed to establish a new, sensitive, and specific ELISA for SARS diagnosis.

Antibodies, Viral ; blood ; Blotting, Western ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Genome, Viral ; Humans ; Immunoglobulin G ; blood ; Nucleocapsid Proteins ; genetics ; immunology ; metabolism ; RNA, Viral ; genetics ; Recombinant Proteins ; isolation & purification ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; SARS Virus ; genetics ; immunology ; isolation & purification ; metabolism ; Severe Acute Respiratory Syndrome ; blood ; diagnosis ; virology

The introduction of artificial intelligence into the medical field is also facing social ethical challenges while promoting changes in the field of health services. To realize the healthy development of medical artificial intelligence, we must consider the ethical issues inherent in the application of artificial intelligence technology in medical services. The article analyzes the ethical issues brought about by medical artificial intelligence from the aspects of security, doctor’s principal status, doctor-patient relationship, and fair benefit. By implementing special supervision, clarifying the principal status of doctors, and strengthening ethical protocols, the application of artificial intelligence in medical services will be guided to promote artificial intelligence to better improve the service capabilities and quality of healthcare system.