Preparation and enhanced photodynamic therapy of supramolecular nanoparticles to overcome tumor hypoxia / 药学学报

The therapeutic effect of tumor photodynamic therapy is severely limited by the hypoxic tumor microenvironment. Inhibiting tumor celloxygen consumption is a more effective way than increasing its oxygen supply to overcome the tumor hypoxia and enhance photodynamic therapy. To carry out this strategy, the supramolecular nanoparticles VER-ATO-SMN loaded with photosensitizer verteporfin (VER), oxygen-consuming inhibitor atovaquone (ATO), and stabilizer polyvinylpyrrolidone (PVP)-K30 were prepared by the nanoprecipitation method, and the optimal prescription was screened and optimized by single factor experiments. The results showed that the optimal prescription for VER-ATO-SMN was ATO∶VER (w/w) = 1∶1, PVP-K30 = 100 mg, N,N-dimethylformamide∶water (v/v) = 1∶10. The morphology, particle size, particle dispersion index and encapsulation efficiency of supramolecular nanoparticles were characterized. The VER-ATO-SMN showed a spherical morphology and was well dispersed. The hydrodynamic size of VER-ATO-SMN was 101.21 ± 4.30 nm as determined by dynamic light scattering (DLS). The encapsulation efficiencies of VER and ATO in VER-ATO-SMN prepared with the optimal prescription were 70.86% and 77.52%, respectively. The VER-ATO-SMN exhibited good laser stability and also showed high stability in conditions which simulated the physiological solution. Compared with free VER and VER liposome, VER-ATO-SMN performed enhanced therapeutic effect at the cell level. The mechanism was that VER-ATO-SMN could effectively incorporate into cells and improving the intracellular oxygen concentration by reducing the oxygen consumption of tumor cells could increase the amount of reactive oxygen species generated by VER mediated photodynamic therapy. The in vivo anticancer efficacy results of tumor-bearing mice suggested that VER-ATO-SMN could effectively inhibit the tumor growth or even completely eliminate the tumor. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of 900 Hospital of the Joint Logistics Team.

Preparation and quality evaluation of fluorocarbon microemulsion-based gel loaded with both 5-aminolevulinic acid and carbon dioxide / 药学学报

To improve the efficacy of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT), a fluorocarbon microemulsion-based gel (FMBG) loaded with both 5-ALA and carbon dioxide (CO2) was prepared in this study. Its physical and chemical properties such as particle size, zeta potential, morphology, pH value and viscosity were characterized. Acid-base titration experiment was used to determine the CO2 loading, a fluorescence derivatization method was established to determine the content of 5-ALA, and the confocal laser scanning microscope and Franz diffusion cell method were carried out to investigate its transdermal ability. Through the laser speckle contrast imaging, the CO2-affected blood flow perfusion of skin was measured. Finally, the skin irritation test was tested by hematoxylin-eosin staining (H&E) method. These results showed that the prepared FMBG was a milky white gel, with an average particle size of 202.4 nm, a zeta potential of -25.3 mV, a pH of 6.0, and a viscosity of 1 062.0 mPa·s. It can be stored stably for seven days at room temperature. The 5-ALA content of FMBG was measured to be approximately equal to 20% (w/w). At room temperature and normal pressure, the CO2 loading content of FMBG was 5.016 mg·L-1, which was 1.5 times as much as that of water. The transdermal absorption experiment and blood perfusion results showed that the FMBG can effectively enable the transdermal delivery of 5-ALA and CO2, and significantly increased the blood perfusion of skin. H&E staining results indicated that FMBG had negligible skin irritation (all animal tests were approved by the Ethics Committee of 900 Hospital of the Joint Logistics Team). In this study, a safe and stable FMBG loaded with both 5-ALA and CO2 was successfully prepared. It was suitable for transdermal application, having the potential of enhancing the efficacy of 5-ALA-mediated PDT.

Surgical Indications of Exploring Optic Canal and Visual Prognostic Factors in Neurosurgical Treatment of Tuberculum Sellae Meningiomas / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tuberculum sellae meningiomas (TSMs) present a special symptom because of the adherence and compression to the optic nerve, optic artery, and the chiasm. A significant number of patients with TSMs appear visual deficits. This study aimed to investigate the surgical indications of exploring the optic canal and visual prognostic factors in the neurosurgical treatment of TSMs.</p><p><b>METHODS</b>Totally 21 patients with TSM, who were operated from September 2007 to August 2011 in the Department of Neurosurgery, Tongren Hospital were enrolled in this study. Results of orbital computed tomography (CT) and magnetic resonance imaging (MRI), visual acuity, Goldmann visual field test, orbital color Doppler flow imaging (CDI) test in these patients were retrospectively analyzed.</p><p><b>RESULTS</b>Visual deficit and optic canal involvement (OCI) were detected in all the 21 patients. Fourteen patients had bone proliferation within the area of the optic canal. After the operation, visual outcomes were improved in 13 patients, unchanged in 7 patients, and deteriorated in 1 patient. All the 21 patients performed orbital CDI test preoperatively, the results showed that if the peak systolic velocity (PSV) of central retinal artery (CRA) value was ≤ 8 cm/s, the visual outcome would be better.</p><p><b>CONCLUSIONS</b>The surgical indications of exploring optic canal in TSM cases included: (1) The neuroimaging evidences of OCI (CT and/or MRI); (2) PSV of CRA in orbital CDI test was ≤ 8 cm/s; (3) visual acuity was below 0.1; (4) visual field deficit. The PSV of CRA in CDI test could be a prognostic factor for visual outcomes of TSMs.</p>

Extracorporeal shockwaves induce osteogenic differentiation of human mesenchymal stem cells by ATP release / 医用生物力学

Objective To investigate whether extracorporeal shockwave could induce differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells by ATP release and the activation of P2X7 receptors. Methods Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase (ALP) activity, osteocalcin (OC) production, and calcium nodule formation. The mRNA expression of P2X7 receptors was determined with real-time RT-PCR. P2X7-siRNA, apyrase, and P2 receptor antagonists were used to evaluate the roles of ATP release and P2X7 receptors in shockwave-induced osteogenic hMSCs differentiation. Results Shockwave treatment released significant amounts of ATP from hMSCs. Shockwaves and exogenous ATP induced hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7-siRNA or selective antagonists prevented osteogenic differentiation of hMSCs. Conclusions Shockwaves can contribute to osteogenic differentiation of hMSCs by realeasing cellular ATP that activate signaling. These research findings provide the theoretical basis for shockwave therapy in treating fracture healing and bone nonunion.

Bone cement injection into tibial condyle for the prevention of degenerative osteoarthritis / 中国骨伤

<p><b>OBJECTIVE</b>To observe therapeutic effects of preventing degenerative osteoarthritis by injecting bone cement into tibial condyle.</p><p><b>METHODS</b>From January 2006 to Junary 2009, 24 patients with degenerative osteoarthritis were treated by injecting bone cement into tibial condyle, including 10 males and 14 females, ranging in age from 46 to 65 years, with an average of 50 years. The mean course of duation was 1 year. HSS scoring system was used to evaluate therapeutic effects preoperatively and one year after follow-up.</p><p><b>RESULTS</b>All patients were followed up over 2 years. HSS score after two years follow-up was 66.65 +/- 6.30, which was higher than that of preoperative 35.70 +/- 4.80. There was no significant difference between preoperation and one year after follow-up in anatomy angle of tibia.</p><p><b>CONCLUSION</b>Bone cement injection into tibial condyle can prevent degenerative osteoarthritis and varus knee.</p>

Craniotomy with endoscopic assistance in the treatment of nasopharygeal fibroangioma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Nasopharygeal fibroangioma (NPF) can be approached through lateral rhinotomy, the middle skull fossa approach and the transcranial-facial combined approach. It is complicated and thus results in more insults, and when adopted, the total resection rate of tumor is still low. The nasal endoscope is minimally invasive, the dead angles of a craniotomy, such as sphenoid sinus, maxillary sinus, and nasopharynx are easily approached by an endoscope. Lateral rhinotomy have to make facial incision and affects maxillary bone development. We combined the craniotomy and endoscopic approach intending to take advantages of the two approaches.</p><p><b>METHODS</b>Twelve NPF patients who underwent craniotomy with endoscopic assistance from March 2002 to July 2008 at the Beijing Tongren Hospital were selected. All patients were male. Their ages ranged from 11 to 33 years. The main symptoms were visual deterioration, exophthalmos, nasal obstruction, epistaxis and pharynx nasalis neoplasm. The diagnosis was based on CT, MRI and digital subtraction angiography (DSA). All patients had intracranial encroachment and all underwent DSA and embolism treatment were taken before surgery. Seven patients had a pterional craniotomy, five had a frontal-temporal-orbital-zygomatic craniotomy. Most of the tumor was resected piecemeal, then removed through the sphenoidal sinus. Finally, using an endoscope in the nasal cavity, tumor in nasal cavity was resected and removed through the sphenoidal sinus, observing the dead angle of the craniotomy and confirming that sinus drainage was unobstructed.</p><p><b>RESULTS</b>The tumor was removed completely in 11 patients and partially resected in one patient because of hemorrhage. One patient had an infection after the operation and one patient had cerebrospinal rhinorrhea 3 years after surgery that was remediated by endoscopic repair.</p><p><b>CONCLUSION</b>Craniotomy with endoscopic assistance in the treatment of NPF was minimally invasive, safe and efficient, and avoided facial incision.</p>

Sphenoid wing meningioma en plaque: report of 37 cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sphenoid wing meningioma en plaque is a special morphological subgroup of intracranial meningiomas, defined by a carpet-like, soft tissue component that infiltrates the dura and invades the sphenoid wing and orbit associated with a significant hyperostosis. This report summarized our experiences in 37 patients with sphenoid wing meningioma en plaque who had been treated with transcranio-orbital approach surgery.</p><p><b>METHODS</b>A retrospective study was made on clinical manifestations, neuroradiological features, and operative techniques in 37 patients undergoing transcranio-orbital approach from Sep. 1998 to Apr. 2009. Patients ages: 16 years to 67 years, 45.5 years in average; sex: 15 males, 22 females. Chief complaints were progressive proptosis and visual acuity deficits. All patients were operated on using a fronto-temporal approach with orbital decompression. The extent of tumor resection and postoperative complications were investigated.</p><p><b>RESULTS</b>Simpson grade II resection was achieved in 9 patients, Simpson grade III in 22 patients and Simpson grade IV in 6 patients. Pathological examination showed 27 (73%) patients were meningothelial meningiomas. After surgery, proptosis improved in all patients, visual acuity improved in 18 patients (69%). Temporary ophthalmoplegia was found in 8 patients, cerebrospinal fluid leak was found in 1 patient. Duration of follow up was from 3 months to 9 years, tumor recurred in 7 patients, and 5 patients underwent second surgery, including two trans-nasal endoscopic surgeries to resect sphenoid sinus-involved tumor. There were no operation-related deaths or other significant complications.</p><p><b>CONCLUSIONS</b>Sphenoid wing meningioma en plaque, mainly meningothelial meningiomas, are more likely to produce adjacent hyperostosis and have characteristic radiological appearances. All the hyperostosis bone of the great wing of sphenoid bone should be removed to prevent recurrence. Extensive tumor removal with bony decompression at the orbital apex can produce satisfactory cosmetic and functional outcome. Close co-operation between the neurosurgeons and the ophthalmologists is important.</p>

Endoscopic transpterygoid intervention of meningoencephalocele within lateral recess of sphenoid / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To report the results of endoscopic transpterygoid intervention of nine patients with meningoencephalocele and cerebrospinal fluid (CSF) leaks within lateral recess of sphenoid sinus (LRSS). The diagnosis, operative techniques and their related problems were discussed.</p><p><b>METHODS</b>Nine hospitalized patients with meningoencephalocele and CSF leaks within lateral recess of sphenoid sinus (LRSS) were included in this paper. Six were male and 3 were female, aged from 27 to 56 years old. Two patients had the histories of endoscopic repair. The preoperative orientation of CSF leaks and meningoencephalocele depended on CT scan and MR cisternography. Endoscopic transpterygoid intervention and the repair of skull base defects were undertaken under general anesthesia.</p><p><b>RESULTS</b>All the operations were successful. One patient had a postoperative intracranial hypertension and Hydrocephalus. Two patients had postoperative ipsilateral facial, upper lip and palatal hypesthesia. One of them had a xerophthalmia. All the symptoms above mentioned relieved gradually 6 months after operation. No recurrence was found during follow -up for 6 to 58 months (mean 25. 6 months).</p><p><b>CONCLUSIONS</b>Endoscopic transpterygoid intervention for meningoencephalocele and CSF leaks within LRSS is a minimally invasive technique and a straightforward approach.</p>

Transcranial approach for resecting spheno-orbital meningiomas / 眼科

Objective To explore the effect and safety of transcranial approach for spheno-orhital meningioma. Design Retro- spective case series. Participants Thirty-two patients being operated with transcranial approach. Twenty-four cases were meningothelial meningiomas, 3 cases were fibrous meningiomas, 1 case was psammomatous meningioma, 2 cases were atypital meningiomas, 2 case were malignant meningiomas. Methods All patients underwent frontal-temporal craniotomy, the involved sphenoid wing bone and peri- orbit were removed to prevent recurrence. The superior orbital fissure and optic canal were decompressed, the dural and periorbital de- feet were repaired by autogenous temporal fascia or artificial dura. Main Outcome Measures Preoperative and postoperative exoph- thalmus and eyeball movement, the extent of tumor resection, the ratio of recurrence. Results The extent of tumor resection: 8 cases were Simpson gradeⅡ, 20 cases Simpson gradeⅢ, 4 cases Simpson grade IV. After surgery, proptosis were improved in all patients, ophthalmoplegia was found in 6 eases. There was no operation-related death or other significant complication. Tumor recurred in 6 cas- es. Conclusions Adequate exposure of the tumor and bony decompression of the cranial nerves can result from transcranial approach, all the involved bone should be removed in order to prevent recurrence. This approach is relatively safe and the ptoptosis are improved significantly. Complete surgical resection is difficult because of the involvement of the orbital apex, superior orbital fissure and cav- ernous sinus.