Background Nanoemulsions (NEs) is one of the most popular ophthalmic colloidal drug delivery system due to its long-term stability, low toxicity and irritancy, considerable capacity for solubilization of lipophilic drug molecules and great potential in bioavailability improvement.The cornea pathway is the main route of intraocular absorption after topical use of NEs.Though NEs possess numerous physiological and physicochemical advantages,the use of NEs cannot always obtain satisfactory results.Objective This study was to investigate the impacts of epithelium and stroma on the corneal permeation of topical ophthalmic terbinafine hydrochloride nanoemulsions (TH-NEs).Methods TH-NEs was prepared by the self-emulsification method.The size and Zeta potential of the oil droplets in the formulation were analyzed using a dynamic light-scattering particle size analyzer.The high performance liquid chromatography (HPLC) was used for the in vitro release study.Sixty New Zealand albino rabbits were randomly divided into intact cornea group and cornea epithelium debrided group.The cornea epithelium of the left eyes was debrided in the cornea epithelium debrided group.The TH-NEs were instilled into the lower conjunctival sac of left eyes.Six rabbits were executed from each group 15,30,60,120 and 240 minutes after dosing,respectively.The corneas were collected and analyzed by HPLC.The fluorescein diacetate (FDA) was used to label the TH-NEs.Two C57BL/6 mice with left cornea epithelium debrided and 2 normal mice were used for the fluorescence tracing study.The fluorescence distribution of FDA labeled TH-NEs was observed by a two-photon laser confocal scanning microscope 30 minutes and 60 minutes after single instillation.Results The average size and Zeta potential of the oil droplets were 51.37 nm and-0.232 7 mV respectively,and 0.482％ of encapsulated drugs was released from the TH-NEs after 12 hours.The peak concentrations of TH in the intact cornea and epithelium debrided cornea were (17.85 ± 2.79) μg/g and (4.40± 1.75) μg/g respectively, which occurred 15 minutes postdose.The drug concentrations in the intact cornea were significantly higher than that in the debrided cornea 15,30,60 and 120 minutes after dosing, with significant differences between them (t =9.998,8.658,6.903,7.576;all at P=0.000).The fluorescence was observed in the cornea epithelium when the cornea was intact.The fluorescence intensity in the superior layer of corneal epithelium was obviously higher than that in the deep layers of corneal epithelium 30 minutes and 60 minutes after dosing.No fluorescence was observed in the cornea stroma of both eyes.Conclusions The cornea epithelium is the main of absorption and distribution position of TH-NEs.The cornea stroma is the dominating permeation barrier for the intraocular transportation of the TH-NEs.The cornea stroma may stop the permeation of TH-NEs by molecular exclusion mechanism.

Objective To establish a tandem affinity purification(TAP) system of innate immune-regulatory protein PKR and analyze PKR function, for the future screen and identification of novel PKR-interaction proteins. Methods PKR gene was amplified by PCR, and then cloned into a mammalian expression vector pcTAP-A. Recombinant pcTAP-PKR was transfected into PKR knock-down(PKRkd) HeLa cells by LipofectAMINE 2000,and the PKR overexpressed HeLa cells were harvested for mitogen-activated protein kinases(MAPK) activation analysis. Cell extracts of PKR overexpressed cells were purified using TAP kit and examined by Western blot. Results Cal modulin resin(CBP) and streptavidin resin(SBP) tagged PKR was detected in PKRkd HeLa cells as early as 24 h upon transfection with pcTAP-PKR, and its expression decreased at later time points. The overexpression of PKR was autophosphorylated, and thus involved in the regulation of MAPK actviation. After small-scale TAP kit purification, PKR protein was detectable by Western blot. Conclusion We have successfully established a TAP system that over-expresses functional PKR, providing a useful tool for the future study on the identification of PKR interacting proteins.

BACKGROUND: Several studies have demonstrated that many American women who are at high risk of developing osteoporosis have higher levels of serum phosphorus. This indicates that some substances which can lower the serum level of phosphorus will supply a new and effective method to prevent and treat osteoporosis.OBJECTIVE: To observe the influences of porcine bone protein on bone mineral density (BMD) and serum levels of calcium and phosphorus in a rat model of osteoporosis.METHODS: Wistar rat models of osteoporosis were established by intramuscular injection of dexamethasone. Rat models were randomly divided into physiological saline, Jiegu Qili tablet, 50, 100, 200 mg/kg porcine bone protein groups. Rats that did not receive any treatments served as normal controls. After 12 weeks of treatment, serum was collected and serum levels of phosphorus and calcium were determined by biochemistry method. At the same time, tibia sections were made to determine tibial DMD by QDR-400 dual energy X-ray absorptiometry and to observe tibia marrow cavity by hematoxylin-eosin staining.RESULTS AND CONCLUSION: There was no significant difference in serum level of calcium among groups (P＞0.05).Compared with the physiological saline group, serum level of phosphorus in the 50, 100, 200 mg/kg porcine bone protein groups was significantly decreased (P ＜ 0.05). BMD was significantly higher in the 50, 100, 200 mg/kg porcine bone protein, Jiegu Qili tablet groups than in the physiological saline group (P ＜ 0.05). The tibia marrow cavity was smallest in the normal control group and largest in the physiological saline group. The tibia marrow cavity was larger in the 50, 100, 200 mg/kg porcine bone protein,Jiegu Qili tablet groups than in the physiological saline group. These results indicate that porcine bone protein cannot change the serum level of calcium, but it lowers serum level of phosphorus, and increases BMD, in a rat model of osteoporosis. However, the dose-dependent effect of porcine bone protein was not observed within the present experimental dosage. In addition, porcine bone protein can also reduce the marrow cavity of the tibia of rats with osteoporosis.

BACKGROUNDPulmonary blastoma is a rare primary malignancy of the lung. It is now recognized in two forms: adult type pulmonary blastoma and childhood pleuropulmonary blastoma. The clinical characteristics, diagnosis and treatments of adult type pulmonary blastoma are discussed in this article.

METHODSThe clinical records of 5 patients with adult type pulmonary blastoma admitted in Cancer Center, Sun Yet-sen University from 1964 to 2004 were analyzed and the literature on pulmonary blastoma was reviewed.

RESULTSThree patients were male and two were female with the ages ranged from 22 years old to 70. Their symptoms consisted mainly of cough, hemoptysis and chest pain. The pulmonary blastomas were mainly manifested as a solitary parenchymal mass of the lung on chest radiograph and CT. None of these patients was diognosed by fibrobronchoscopy nor sputum cytology. Three patients underwent lobectomy, one underwent pneumonectomy, and these four patients underwent mediastinal lymph node resection also. The fifth one received wedge resection and postoperative chemotherapy. At the end of follow-up, three patients died and two was alive, and the survival time was from 6 months to 11 years.

CONCLUSIONSPulmonary blastoma is difficult to be diagnosed before operation. Surgery is the best therapeutic choice up to now. It has poor response to radiotherapy and chemotherapy. The prognosis of patient with pulmonary blastoma is variable.

Objective The toxicological compatibility of Aconiti Carmichaeli Radix, as a toxic Chinese medicinal herb, combined with the other ingredients in Sini Decoction was investigated to elucidate the rationality of the combination of the ingredients in Sini Decoction from toxicological point of view. Methods Three kinds of experiments, acute toxicity in mice, heart toxicity in rats and aconitines level in water extract of Sini Decoction and its ingredients including Aconiti Carmichaeli Radix alone and its combination with licorice or dried ginger were adopted in this study. In the toxicological experiments, LD50 values for the acute toxicity test and TD50 values for the heart toxicity (arrhythemia as a parameter) of Sini Decoction, Aconiti Carmichaeli Radix alone and its combination with licorice or dried ginger were comparatively determined. And levels of individual aconitines of the water extracts from Sini Decoction, Aconiti Carmichaeli Radix alone and its combination with licorice or dried ginger were measured, respectively. Results The LD50 and TD50 of the combination of Aconiti Carmichaeli Radix and licorice in Sini Decoction were found to be higher than Aconiti Carmichaeli Radix alone or Sini Decoction, while the LD50 and TD50 of the combination of Aconiti Carmichaeli Radix and dried ginger appeared to be not different from those of Aconiti Carmichaeli Radix alone. The level of the main toxic compound of the water extracts for the combination of Aconiti Carmichaeli Radix and licorice, and Sini Decoction was lower than that of Aconiti Carmichaeli Radix alone and its combination with dried ginger. Conclusion The combination of Aconiti Carmichaeli Radix and licorice can attenuate the toxicity of Aconiti Carmichaeli Radix.

Covalently modified drugs,which exert their pharmacological effects by covalently binding to the targets,have been avoided as far as possible for a long time in drug design due to the potential off-target effects and other side-effects.With the in-depth study of binding modes of market blockbuster covalent drugs,more and more attention has been concentrated on covalently modified drugs.Current challenges remain in development of potent selective covalently modified drugs with fewer adverse effects.This paper reviews the classification of some covalently modified drugs,the drug-target binding modes and the new strategies of designing covalently modified drugs,in order to provide reference for rational design of covalent drugs.

Phased array transducers are very attractive because the beam generated by the arrays can be electronically focused and steered. The present work characterizes far-field 2D properties of phased array system by functions that are deduced from rectangle source, rectangle line array and phased array based on point source. Results are presented for the distribution of ultrasound intensity on plane xoz and on x-axis by simulation using numerical calculation. It is shown that the shape of response of rectangle line array is modulated by the single array element. It is also demonstrated that the delay time of phased array is the key to steer the beam, sacrificing the value of main lobe and increasing the number of side lobes.
Computer Simulation ; Models, Theoretical ; Transducers ; Ultrasonics ; instrumentation ; methods

Objective To introduce the operation skills of tail vein injection in conscious rats , and improve the success rate of ingection .Methods The rat was fixed by the operator with a self-made binding clothes , one person assists to fix the rat tail, one person performs puncture , and one person performs injection .During the injection process , we should minimize the injury to the rat tail and the stress caused by operation , strictly limit the needle point , the number of puncture , the maximum dose and injection speed , and to make the needle position away from the injection site to avoid contamination and waste of the drug solution .Results The operation method was successfully established and it was fast , stable, with good repeatability and high degree of coordination .Conclusion This operation is rapid, reliable and stable, worthy of recommendation , especially for the intravenous injection of expensive drugs .

BACKGROUND:Pulsed electromagnetic field is a non-invasive and non-radiative treatment method.Clinical use of pulsed electromagnetic fields in the treatment of orthopedic diseases has achieved certain results. OBJECTIVE:To review the current clinical application of the pulsed electromagnetic field in the treatment of orthopedic diseases,providing a scientific theoretical basis for the clinical treatment of orthopedic diseases. METHODS:The first author used a computer to search PubMed,CBM,Cochrane Library,CNKI,and WanFang Data for related studies on the pulsed electromagnetic field in the treatment of orthopedic diseases,using the keywords of"pulsed electromagnetic field,orthopedics,osteoarthritis,osteoporosis,bone healing,electromagnetic navigation"in English and Chinese.For the literature related to the same content,recent publications were selected.A total of 69 articles were selected from the search results for review. RESULTS AND CONCLUSION:Pulsed electromagnetic field has a definite curative effect on fracture healing.It can be used in the treatment of osteomyelitis by antibacterial,bactericidal,anti-inflammatory and promoting bone healing,and can inhibit osteoporosis and its progress.In addition,the treatment of early osteoarthritis,femoral head necrosis and postoperative rehabilitation of late joint replacement through various ways can become a treatment for orthopedic diseases.However,the therapeutic mechanism of the pulsed electromagnetic field for a variety of orthopedic diseases is still unclear,and most of the research is still in the primary stage.In the future,it is still necessary to obtain more reliable evidence from high-quality research and clinical trials to provide a more perfect basis for the clinical treatment of orthopedic diseases.

Objective:To understand the current state of financial toxicity and suicide risk in head and neck cancer patients, to investigate the correlation between the level of financial toxicity and suicide risk in head and neck cancer patients, and to provide a basis for reducing the level of financial toxicity and the risk of suicide in head and neck cancer patients.Methods:A cross-sectional survey was conducted, from March 1 to July 31, 2022, 150 head and neck cancer patients were selected from Oncology Department of East Hospital Affiliated to Tongji Universityby by convenient sampling method. The survey was carried out by means of the general questionnaire, Comprehensive Score for Financial Toxicity based on the Patient-Reported Outcome Measures (COST-PROM), Cancer Suicide Risk Scale (CSRS), and then analysis the datum.Results:The score of COST-PROM of 150 head and neck cancer patients was (18.00 ± 6.12) points, and the score of CSRS of head and neck cancer patients was (36.31 ± 8.51) points. The total score of economic toxicity was significantly negatively correlated with the total score of suicide risk and its dimensions ( r values were -0.446 to 0.235, all P<0.05). The total score of suicide risk was negatively correlated with the total score of economic toxicity and the scores of each dimension ( r values were -0.446 to -0.251, all P<0.05). Conclusions:Patients with head and neck cancer were at higher risk of suicide, and financial toxicity was a significant contributing factor to suicide risk, with higher levels of financial toxicity associated with a higher risk of suicide. Reducing the level of financial toxicity in patients with head and neck cancer has important implications for reducing their risk of suicide.