Objective: To determine the prescription technology of gastrodin starch microsphere and investigate its nasal mucoadhesion and in vitro release characteristics. Methods: Gastrodin starch microspheres were prepared by compound emulsion crosslinking method. According to the particle diameter, drug loading efficiency (DLE), and entrapment efficiency (EE), the best prescription technology was selected by using single-factor investigation and uniform design. Using toad palate mucosa as model and average residence time as indicator, mucoadhesion of gastrodin starch microsphere was evaluated. Using gastrodin API as a control, paddle method was applied to in vitro release test of gastrodin starch microspheres. The content of gastrodin was determined to calculate the cumulative release percentage. In addition, the curve of drug release in vitro was fitted with different release model to analyze the in vitro release characteristics of gastrodin starch microsphere in nasal cavity, synthetically. Results: The optimum prescription and preparation technology of gastrodin starch microsphere were as follows: gastrodin 2.0 g, starch 4.5 g, liquid paraffin 100.0 mL, Span80 3.5 g, ECH 5.1 mL, preparation temperature 40℃, and rotational speed 1000 r/min. The particle diameter of gastrodin starch microsphere was (47.69±1.92) μm, the DLE and EE of microsphere were (9.78±0.70)% and (35.72±3.28)%, respectively. It was about (176.92±23.25) s that in adhesive powder resided in nasal cavity, which translated into human nasal residence time was just 20-30 min, while the average residence time of gastrodin starch microspheres was extended to (944.33±68.29) s, translated into human nasal residence time was about 3 h. The cumulated release percent of gastrodin starch microspheres was more than 90% in 3 h. Compared with other in vitro release models, Weibull model was the fittest model to gastrodin starch microspheres, the t50 of gastrodin starch microspheres was 40.08 min, and t90 was 245.73 min. Conclusion: Gastrodin starch microspheres prepared with optimum prescription technology have uniform particle diameter, high DLE and EE. Microspheres have good mucoadhesion and sustained release, ensure that gastrodin release gently and completely during the nasal retention period.

The stability of pharmaceutical preparations prepared Chinese medicine liposomes by liposome novel technology combined with traditional Chinese herbs is the main contents of quality study, not only affects preparations molding, but also relates to the efficiency and safety of traditional Chinese medicine. From the view of main influencing factors of stability about the Chinese medicine liposomes and combining with literatures published in home and abroad in recent years, the article analyzes, arranges and sums up measures of improving the stability of Chinese medicine liposomes, to provide reference for the study on the preparation of Chinese medicine liposomes.
Drug Combinations ; Drug Compounding ; Drug Stability ; Drug Storage ; Drugs, Chinese Herbal ; administration & dosage ; Hydrogen-Ion Concentration ; Liposomes ; chemistry ; Nanoparticles ; Particle Size ; Quality Control ; Technology, Pharmaceutical ; methods

Objective To analyze the characteristics,electroencephalographic(EEG)features,neuroimaging findings,therapeutic effects and prognoses of 114 cases of idiopathic nocturnal frontal lobe epilepsy (NFLE). Methods The clinical data of 114 patients with idiopathic NHLE admitted in the epilepsy outpatient department from June,1999 to January,2007 were collected and analyzed. Results Idiopathic NFLE was clinically characterized by nocturnal clustered,postural or dystonic seizures and complex motor activities.The interictal routine EEG in 22.9% and dynamic EEG in 28% of the cases in wakefuIness and the interictal dynamic EEG in 38% of tbe cases in sleep showed frontal lobe epileptiform discharge,which was found in the EEG during seizure attacks in66.7% of the cases.Drug therapy was effeclive in 79.8% of the cases.with 29.7% of the cases showing complete seizure control. Conclusions Idiopathic NFLE has distinct clinical features wim relatively low rate of EEG abnormality during seizure attack or the interictal period.Frontal lobe epilepsy is more likely to occur in sleep,and sleep EEG is therefore of much importance in the diagnosis of idiopathic NFLE.

Objective: To investigate the clinical effect and safety of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in the treatment of previously untreated HBeAg-positive chronic hepatitis B (CHB) patients with a high viral load. Methods: A retrospective analysis was performed for the clinical data of 152 HBeAg-positive CHB patients with a high viral load (HBV DNA≥10⁶ IU/ml) who were firstly treated with ETV (ETV group) or TDF (TDF group), with 76 patients in each group. The serum levels of alanine aminotransferase (ALT), HBV DNA, HBeAg, anti-HBe, creatinine, and creatine kinase were measured at baseline, and the patients were followed up and evaluated at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96 of treatment. The Kaplan-Meier survival curves were used to analyze cumulative complete virologic response, HBeAg seroconversion, and ALT normalization rate. The Cox proportional hazards regression model was used to identify the influencing factors for virologic response. P < 0.05 was considered statistically significant. Results: There were no significant differences in ALT normalization rate between the ETV group and the TDF group at weeks 4, 12, 24, 48, 72, and 96 of treatment (18.1%/55.6%/83.3%/90.3%/93.1%/97.2% vs 16.0%/53.6%/75.4%/94.2%/100%/100%, P > 0.05). There were also no significant differences in virologic response rate between the ETV group and the TDF group at weeks 48 and 96 of treatment (89.5%/97.3% vs 93.4%/98.7%, P > 0.05). The multivariate analysis showed that the baseline parameters were not predictive factors for virologic response. At week 48 of treatment, the TDF group had a significantly higher HBeAg seroconversion rate than the ETV group (14.5% vs 3.9%, P = 0.048); at week 96 of treatment, there was no significant difference in HBeAg seroconversion rate between the two groups (15.8% vs 7.9%, P = 0.132). The Kaplan-Meier survival analysis showed that there were no significant differences between the two groups in cumulative ALT normalization rate, cumulative HBV DNA undetectable rate, and cumulative seroconversion rate. Only one patient in the ETV group experienced virologic breakthrough from weeks 60 to 72 of treatment, and there were no serious adverse reactions. Conclusion TDF and ETV had similar clinical effects, HBeAg seroconversion rate, and safety in previously untreated HBeAg-positive CHB patients with a high viral load.

Objective To establish a comprehensive method combining physical model experiment and numerical simulation for studying airflow state of upper respiratory tract. Methods Based on CT medical images published online, a three-dimensional (3D) model of human upper respiratory tract was reconstructed. Based on 3D printing technology, an experimental model of the upper respiratory tract was established and the flow process of respiration was measured. A numerical simulation model was created based on the meshing of upper respiratory tract model and the turbulent Realizable k-ε model. Results Firstly, the result of numerical simulation was compared with the experimental conditions, and good agreement was achieved. The numerical simulation results showed that the airflow in respiratory process was in a parabolic shape; the distribution of flow field, pressure on wall and vortex structure were different between inspiratory and expiratory phases; there were air residues in the upper and lower nasal passages during the respiratory exchange process. In addition, the effects of airflow on physiological environment of the upper respiratory tract were preliminarily analyzed through the steak line, pressure field and vortex structure distribution. Conclusions The method proposed in this paper has the characteristics of pertinence, rapidity and accuracy, which gives full play to the advantages of reliable physical experiments and fine numerical simulation, and is applicable for studying different problems of the upper respiratory tract in different cases, with a high value for personalized diagnosis and treatment in clinic.

Aim To explore the key genes of osimertinib aequired resistanee in non-small eell lung eaneer eells based on transcriptomics, anrl to analyze the significance in osimertinib resistant eells. Methods Hu man lung cancer HI975 cells and osimertinib resistant HI 975/OR cells were cultured in vitro. The effect of osimertinib and ferroptosis inducers on cell viability was measured by CCK-8 assay. The difference in gene expression was measured by transcriptomics. Hie expression levels of ferroptosis-related proteins were measured by Western blot. Results Osimertinib j eould inhibit the proliferation of HI975 eells and HI 975/OR eells in different concentrations, and HI975 cells were more sensitive. Transcriptomics analysis revealed remarkable differences in gene expression levels between HI975 and H1975/OR cells, among which the ferroptosis pathway was most significant. Western blot assay validated that different degrees of change existed in the expression levels of ferroptosis-re- lated proteins in HLF-1 , H1975 and H1975/OR eells. After the treatment of ferroptosis inducers RSL3 and Erastin, H1975/OR cells showed higher sensitivity, while little significance was observed on HI975 cells. Conclusions There were significant differences between HI975 lung cancer cells and osimertinib resist-ant H1975/OR cells on the gene expression levels, and the ferroptosis pathway plays an important role in acquired resistance to osimertinib.

Abstract】 【Objective】To investigate the effect and mechanism of ginsenoside Rb1 attenuating human umbilical vein endothelial cells(HUVEC) senescence induced by high glucose through Sirt3/SOD2 pathway.【Methods】The senescence of HUVEC induced by high glucose(40 mmol/L)was assessed by senescence-associated β-galactosidase(SA-β-Gal)staining,and the expression of plasminogen activator inhibitor 1(PAI-1)and P16. Annexin V-FITC/PI was performed to measure apoptotic effect. The expression of sirtuins 3(Sirt3)and superoxide dismutase 2(SOD2)was detected by western blot. Meanwhile,the level of intracellular malondialdehyde(MDA)and the activity of SOD2 were measured.【Results】Treatment of HUVEC with high glucose for 24 hours induced premature senescence instead of apoptosis,as indicated by a larger proportion of the cells stained with SA-β-Gal and the up-regulated expression of PAI-1 and P16. Pretreatment of HUVEC with ginsenoside Rb1(40 μmol/L)could reverse endothelial cell senescence,as indicated by the reduced SA-β-Gal positive cells and the down-regulated expression of PAI-1 and P16. Furthermore,ginsenoside Rb1 pretreatment upregulated the protein expression of Sirt3 and SOD2,and eventually increased the activity of SOD2 and decreased the level of MDA.【Conclusion】Ginsenoside Rb1 could antagonize high glucose-induced premature senescence of HUVEC via Sirt3/SOD2 signaling pathway.

OBJECTIVETo search the evidence for the presence of superantigen of Staphylococcus aureus enterotoxin (SE) in the pathogenesis of nasal polyposis.

METHODSIn a cohort of population composed of 42 cases who belonged to three groups: nasal polyposis, simple chronic rhinosinusitis (CRS), and control group without any rhinopathy, detecting the specific IgE against SE-A and B (SEA and SEB), total IgE (TIgE), eosinophilic cationic protein (ECP) of the local mucosa by means of FRAST (UniCAP system), as well as the serum TIgE, and serum anti-SEA and SEB SIgE (only in 8 cases); meanwhile the secretion culture was performed for aerobic bacteria from the middle meatus.

RESULTSThere was no evidence to support that SE played as a superantigen in all mucosa samples (42 cases) and 8 cases serum samples out of the 42 patients. The range of TIgE in mucosa was 4.59 -70.21 kIU/2 mg tissue protein, the mean was (17.85 +/- 14.31) kIU/2 mg tissue protein; in serum the total IgE was 7.44 - 344.00 kIU/L, the mean was (88.65 +/- 80.03) kIU/L The positive culture of Staphylococcus aureus was obtained from only 3 cases from secretion of middle meatus (1 from nasal polyps, 2 from CRS). There was no significance statistically among the three groups on the tissue fluorescence value of SIgE for SE, the means of tissue TIgE and ECP.

CONCLUSIONSNo evidence was found to support the role of SE acting as a superantigen among our cases who did not have persistent asthma. It is suggested that further study and investigation is required to prove the superantigen Hypothesis in the pathogenesis of NPs.

Adolescent ; Adult ; Aged ; Antibodies, Bacterial ; blood ; Enterotoxins ; immunology ; Female ; Humans ; Immunoglobulin E ; blood ; Male ; Middle Aged ; Nasal Polyps ; immunology ; microbiology ; Sinusitis ; immunology ; microbiology ; Staphylococcus aureus ; immunology ; isolation & purification ; Superantigens ; blood ; Young Adult

Objective:To observe the effect of modified Guilu Erxianjiao decoction combined with cisplatin on the immune function， resistance-related genes and interleukin-7（IL-7）-mediated Wnt/β-serial protein（β-catenin）signaling pathway in Lewis lung cancer mice by establishing a mouse model of Lewis lung cancer with deficiency of both Qi and Yin. And the anti-cancer mechanism of modified Guilu Erxianjiao decoction was clarified， so as to provide a basis for its clinical application. Method:A Lewis lung cancer mouse model （type of deficiency of both Qi and Yin） was established. Mice were divided into a normal group （no modeling）， a model group （saline solution）， a cisplatin group （cisplatin， 2 mg·kg^-1）， a traditional Chinese medicine （TCM） group （modified Guilu Erxianjiao decoction， 19.63 g·kg^-1·d^-1）， and a combined group （modified Guilu Erxianjiao decoction， 19.63 g·kg^-1·d^-1 + cisplatin， 2 mg·kg^-1）. The 10 mice in each group were administered separately for 21 days of intervention. The general conditions and organ indexes of mice were observed， and tumor inhibition rate was calculated. CD4⁺CD25⁺ regulatory T cell （CD4⁺CD25⁺ Treg） were detected by flow cytometry， the IL-7 level of cytokines in serum was detected by enzyme linked immunosorbent assay（ELISA）， and real-time quantitative polymerase chain reaction（Real-time PCR） was used to detect the gene expression level of drug resistance-related genes P-glycoprotein（P-gp）， and multidrug resistance protein1（MRP1）in tumor tissues. The protein expression of Wnt/β-serial protein（β-catenin）signaling pathway in tumor tissues were detected by Western blot. Result:In the TCM group and the combined group， the food intake increased， the mental state was better， the response was sensitive， and the body weight increased. Compared with the cisplatin group， the thymus index and spleen index in the combined group were significantly increased （P<0.01）， and the tumor inhibition rate of the combined group was significantly increased （P<0.01）. Compared with the cisplatin group， the percentage of CD4⁺CD25⁺Treg/CD4⁺ in the TCM group and the combined group was significantly reduced （P<0.01）， and IL-7 in the TCM group and the combined group was significantly increased （P<0.01）. Compared with the cisplatin group， the expressions of P-gp and MRP1 genes in the TCM group and the combined group were significantly reduced （P<0.05， P<0.01）， and the protein expressions of secretory glycoprotein1（Wnt1）and β-serial protein（β-catenin）in the TCM group and the combined group were significantly reduced （P<0.01）. Conclusion:The combined use of modified Guilu Erxianjiao decoction and cisplatin can significantly inhibit the growth of tumors in mice with Lewis lung cancer， and its mechanism of action may be related to the efficacy of m odified Guilu Erxianjiao decoction in relieving the body's immunosuppressive state， promoting the body to produce IL-7， regulating IL-7-mediated Wnt/β-catenin signaling pathway and reducing the expression of resistance-related genes in lung cancer tissues.

OBJECTIVETo investigate the effects of resveratrol (RES) on apoptosis of human periodontal ligament cells (HPLC).

METHODSHPLC were subjected to oxidative injury induced by H2O2 for 24 h after pretreatment with different concentration of RES. HPLC were then divided into the control, model, vector, RES 1, 10, 30, 50 micromol/L treatment group. The viability of the HPLC was determined by methyl thiazolyl tetrazolium (MTT) method. Lactate dehydrogenase (LDH) rate and malondialdehyde (MDA) in the culture medium, superoxide dismutase (SOD) in the HPLC homogenate were evaluated by spectrophotometry. The apoptotic HPLC was detected by flow cytometry (FCM) and calculated by relative apoptosis rate. Bax and Bcl-2 protein levels were detected by Western blotting.

RESULTSRES increased the cell survival rate after H2O2 injury. The survival rate of RES 30 micromol/L group was (86.1 +/- 4.1)% and the model group was (54.6 +/- 4.0)%, which was significantly different between the two groups (P < 0.01). The LDH leakage rate and MDA content of the RES 30 micromol/L group were (32.6 +/- 2.0)% and (1.70 +/- 0.21) micromol/L, which were significantly different with that in the model group (P < 0.01). At the same time RES could remarkably restore the vitality of SOD in the HPLC. RES increased Bcl-2 and reduced the expression of Bax protein. The apoptosis rate of the RES 30 micromol/L group and model group was (14.84 +/- 1.36)% and (64.37 +/- 2.34)%, respectively (P < 0.01). The protective effect of RES on the cell apoptosis was in a dose-dependent manner, reaching peak at a concentration of 30 micromol/L (P < 0.01).

CONCLUSIONSRES reduced oxidative stress and apoptosis in an experimental HPLC injury model induced by H2O2. RES plays a key role in the HPLC protection against oxidative injury.

Apoptosis ; drug effects ; Cell Survival ; drug effects ; Flow Cytometry ; Humans ; Hydrogen Peroxide ; In Vitro Techniques ; L-Lactate Dehydrogenase ; analysis ; Malondialdehyde ; analysis ; Oxidants ; Oxidative Stress ; drug effects ; Periodontal Ligament ; cytology ; drug effects ; Stilbenes ; pharmacology ; Superoxide Dismutase ; analysis ; bcl-2-Associated X Protein ; analysis