The aim of this study is to prepare hyaluronic acid (HA) modified core-shell liponanoparticles (pHA-LCS-NPs) as gene delivery system and investigate its gene transfection efficiency in human retinal pigment epithelium (ARPE-19) cells in vitro. The pHA-LCS-NPs was prepared by firstly hydrating dry lipid film with CS-NPs suspension to get LCS-NPs, then modifying the lipid bilayer with HA by amidation reaction between HA and dioleoyl phosphatidylethanolamine (DOPE). Its morphology, particle size and zeta potential were investigated. XTT assay was used to evaluate the cell safety of different vectors in vitro. The gene transfection efficiency of pHA-LCS-NPs modified with different contents of HA was investigated in ARPE-19 cells with green fluorescent protein (pEGFP) as the reporter gene. The results showed that the obtained pHA-LCS-NPs exhibited a clear core-shell structure with the average particles size of (214.9 +/- 7.2) nm and zeta potential of (-35 +/- 3.7) mV. The 24 h cumulative release of gene from pHA-LCS-NPs was less than 30%. After 48 h incubation, gene transfection efficiency of pHA-LCS-NPs/pEGFP was 1.81 times and 3.75 times higher than that of CS-NPs/pEGFP and naked pEGFP, respectively. Also no obvious cytotoxicity was observed on pHA-LCS-NPs. It suggested that the pHA-LCS-NPs might be promising non-viral gene delivery systems with high efficiency and low cytotoxicity.
Cell Survival ; Gene Transfer Techniques ; Genes, Reporter ; Genetic Vectors ; Green Fluorescent Proteins ; metabolism ; Humans ; Hyaluronic Acid ; chemistry ; pharmacology ; Lipids ; Nanoparticles ; Particle Size ; Phosphatidylethanolamines ; chemistry ; pharmacology ; Retinal Pigment Epithelium ; drug effects ; Transfection

The purpose of this study is to prepare galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles (GPEM) to enhance the antitumor efficacy against hepatocellular carcinoma cells. The irinotecan (CPT-11) loaded mesoporous silica nanoparticles (MSNs) was coated with the Gal-P123 modified functional lipid bilayer by thin-film dispersion method. Nanoparticles were characterized with particle size, zeta potential, morphology and drug release in vitro. Afterwards, the cell uptake, intracellular concentration of CPT-11, cell apoptosis rate and cytotoxicity were evaluated on human hepatocellular carcinoma cell line Huh-7. The results showed that MSNs were coated with intact lipid bilayers and the nanoparticles had clear core-shell structure. GPEM is stable with the mean particle size of (78.01 +/- 2.04) nm. The low leakage rate in normal physiological conditions in vitro is contributed to the protection of stable lipid bilayer, and the fast drug release in acid environment due to the destruction of the lipid bilayer. On the cell level, the vector could improve the intracellular CPT-11 concentration by 4 times because of the functional lipid bilayer. The high CPT-11 concentration led to the increasement of apoptosis rate by 48.6%, and the reduction of half maximal inhibitory concentration (IC50) values of CPT-11 by 2 times, indicating stronger cell cytotoxicity.
Antineoplastic Agents ; chemistry ; pharmacokinetics ; Apoptosis ; Camptothecin ; analogs & derivatives ; chemistry ; pharmacokinetics ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Humans ; Lipid Bilayers ; chemistry ; Liver Neoplasms ; drug therapy ; pathology ; Nanoparticles ; chemistry ; Particle Size ; Silicon Dioxide ; chemistry

Coronary Sinus ; abnormalities ; Humans ; Male ; Middle Aged ; Subclavian Vein ; Vena Cava, Superior

The rhizome of Panax japonicus var. major have been used as the natural medicinal agent by Chinese traditional doctors for more than thousand years. Most of the therapeutic effects of P. japonicus var. major had been reported due to the presence of tetracyclic or pentacyclic triterpene saponins. In this study, Illumina pair-end RNA-sequencing and de novo splicing were done in order to understand the pathway of triterpenoid saponins in this species. The valid reads data of 15. 6 Gb were obtained. The 62 240 unigenes were finally obtained by de novo splicing. After annotation, we discovered 19 unigenes involved in ginsenoside backbone biosynthesis. Additionally, 69 unigenes and 18 unigenes were predicted to have potential function of cytochrome P450 and UDP-glycosyltransferase based on the annotation results, which may encode enzymes responsible for ginsenoside backbone modification. This study provides global expressed datas for P. japonicus var. major, which will contribute significantly to further genome-wide research and analysis for this species.
Gene Expression Profiling ; Panax ; genetics ; Saponins ; biosynthesis ; Sequence Analysis, RNA

Abstract?AlM: To observe the effects of Shuangdanmingmu capsule on VEGF expression and retinal vascular morphology in rats with diabetic retinopathy ( DR) .?METHODS: DR rats were fed with Shuangdanmingmu capsule. By comparing with the normal group, the model control group, and positive control group, the effect of Shuangdanmingmu capsule on retinal tissue of DR rats was observed under electron microscopy. After HE staining, retinal structure was observed under the light microscope. lmmunohitochemical staining was used to detect the VEGF expression in retina.?RESULTS:Two months after treatment, the layers tissue of retina presented mild edema, capillary pericytes performed edema, mitochondria showed mild swelling and less clear structure, some endothelial cells showed slight proliferation in Shuangdanmingmu group. Compared with the normal group, the expression level of VEGF in retina increased in the other groups, especially in model control group. A significant differential in expression of VEGF was found between Shuangdanmingmu group, positive control group and model control group (P<0. 01).? CONCLUSlON: Shuangdanmingmu capsule can effectively improve the retinal microvascular, reduce edema and necrosis of each layer of retina, improve the ultrastructure of retina's tissue and inhibit VEGF expression in DR rats.

OBJECTIVETo explore the molecular mechanism via which the chemotherapeutic drug hydroxyurea (HU) enhances K562 cell apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

METHODSChronic myelogenous leukemia-derived K562 and SVT-35 cells were treated with recombinant soluble TRAIL (rsTRAIL) alone or combined with HU for a time course, and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-4-sulfophenyl-2H-tetrazolium-phenazine methosulphate assay. Western blot was performed to analyze the activation of apoptosis-related protein kinases and the expression of apoptosis inhibitor molecules.

RESULTSThe survival rates of SVT-35 and K562 cells treated with 1 μg/ml rsTRAIL for 24 hours were 32% and 93%, respectively. HU significantly increased the sensitivity of K562 cells to rsTRAIL cytotoxicity. Combination of rsTRAIL and HU resulted in the phosphorylation of rat sarcoma (RAS), mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase and in the significant reduction of apoptosis-inhibited molecule Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 in K562 cells.

CONCLUSIONSHU enhanced K562 cell sensitivity to rsTRAIL is mediated by Ras-MEK-ERK signaling pathway. Expression of antiapoptotic proteins cellular Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 is also down-regulated during this process. These results may through light on the therapeutic study of human chronic myelogenous leukemia.

Apoptosis ; drug effects ; physiology ; CASP8 and FADD-Like Apoptosis Regulating Protein ; metabolism ; Humans ; Hydroxyurea ; pharmacology ; Inhibitor of Apoptosis Proteins ; metabolism ; K562 Cells ; MAP Kinase Signaling System ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology

Objective: To explore the current situation and related factors of AIDS discrimination among junior medical students in Jiangxi Province, so as to provide a reference for effective AIDS anti discrimination intervention measures in medical colleges. Methods: Using a convenience sampling approach, 2 484 medical students were selected from five universities in Jiangxi Province from July to August 2023. An anonymous survey was conducted using a general information questionnaire, a AIDS knowledge questionnaire, and the Chinese version of Zelaya s AIDS Stigma Scale. Independent sample t-tests and analysis of variance were carried out to analyze the level of AIDS discrimination among medical students with different characteristics. Multiple stepwise regression analysis was performed to identify the related factors of AIDS discrimination. Results: The total score of AIDS discrimination among medical students was (2.55±0.67). The dimension with the highest score was fear of contracting the disease (2.89±1.01). The results of the multiple stepwise regression analysis showed that the factors related to AIDS discrimination included gender ( β = -0.17 ), grade ( β =-0.08), being an only child or not ( β =-0.04), whether knowing about AIDS knowledge or not ( β =0.22), willingness to use condoms during sexual activity ( β =0.07), willingness to participate in school sexual health knowledge based activities ( β =0.05) and the perceived importance of selfhealth ( β =0.11) ( P <0.05). Conclusions AIDS discrimination is prevalent among junior medical students in Jiangxi Province. Efforts should be undertaken to enhance humanistic education and relevant knowledge dissemination among junior medical students to reduce the level of AIDS discrimination.

Objective To study the cardiotoxicity of trastuzumab in human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients.Methods We retrospectively collected the clinical data of general characteristic,left ventricular ejection fraction (LVEF) and clinical efficacy in 102 HER2 positive metastatic breast cancer patients treated with trastuzumab and analyzed the factors which influence the changes of LVEF and the incidence of cardiotoxicity induced by trastuzumab.Results In all of the 102 patients,the complete remission and partial remission were 7 cases (6.86％) and 73 cases (71.57％) in patients firstly treated with trastuzumab-based regimens respectively.The LVEF value was (72.85 ± 4.64) ％ at baseline and decreased to (66.05 ±5.96)％ and (65.15 ±3.38)％ as the valley points at21 and 39 months in patients who continually used trastuzumab.The progression free (PFS) of the first use of trastuzumab containing regimen and trastuzumab usage time were the clinical factors influencing the LVEF decreased value (P ＜ 0.05).The cumulative incidence of trastuzumab associated cardiotoxicity (TACT) was 14.71％ (15 cases) in the whole course of LVEF monitoring.All patients had no occurrence of heart failure and trastuzumab treatment related death caused by trastuzumab.Conclusion The heart function deceased and recovered periodically under treatment with trastuzumab in metastatic breast cancer.The incidence of cardiotoxicity was stable.Long term use of trastuzumab was well tolerated and safe.

OBJECTIVETo investigate the feasibility of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using hybrid internal fixation of pedicle screws and a translaminar facet screw for recurrent lumbar disc herniation.

METHODSFrom January 2010 to December 2011, 16 recurrent lumbar disc herniation patients, 10 male and 6 female patients with an average age of 45 years (35-68 years) were treated with unilateral incision MIS-TLIF through working channel. After decompression, interbody fusion and fixation using unilateral pedicle screws, a translaminar facet screw was inserted from the same incision through spinous process and laminar to the other side facet joint. The results of perioperative parameters, radiographic images and clinical outcomes were assessed. The repeated measure analysis of variance was applied in the scores of visual analogue scale (VAS) and Oswestry disablity index (ODI).

RESULTSAll patients MIS-TLIF were accomplished under working channel including decompression, interbody fusion and hybrid fixation without any neural complication. The average operative time was (148 ± 75) minutes, the average operative blood loss was (186 ± 226) ml, the average postoperative ambulation time was (32 ± 15) hours, and the average hospitalization time was (6 ± 4) days. The average length of incision was (29 ± 4) mm, and the average length of translaminar facets screw was (52 ± 6) mm. The mean follow-up was 16.5 months with a range of 12-24 months. The postoperative X-ray and CT images showed good position of the hybrid internal fixation, and all facets screws penetrate through facets joint. The significant improvement could be found in back pain VAS, leg pain VAS and ODI scores between preoperative 1 day and postoperative follow-up at all time-points (back pain VAS:F = 52.845, P = 0.000;leg pain VAS:F = 113.480, P = 0.000;ODI:F = 36.665, P = 0.000).

CONCLUSIONRecurrent lumbar disc herniation could be treated with MIS-TLIF using hybrid fixation through unilateral incision, and the advantage including less invasion and quickly recovery.

Adult ; Aged ; Bone Screws ; Feasibility Studies ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Intervertebral Disc Displacement ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Spinal Fusion

Objective: To investigate the deposition rate of Artemisia pollen in different nasal cavity regions and its influence factors in residents of northwest China. Methods: Thirty healthy adults from northwest China were enrolled. The computational fluid dynamics (CFD) and discrete phase model (DPM) were used for numerical simulation of nasal structures. The pollen deposition fraction in each anatomical part was counted and the effects of pollen density and breathing rate on deposition were analyzed. SPSS 19.0 software was used for statistical analysis. Results: The hottest deposition parts of Artemisia pollen were nasal septum (30.70%±12.27%), vestibule (27.45%±8.21%), middle turbinate area (13.59%±8.98%) and nasopharynx (7.14%±5.90%). When the inspiratory flow rate increased to 30 L/min, the deposition rates of pollen in nasal vestibule and nasal septum were significantly higher than that at the rate of 15 L/min (43.20%±11.14% vs 27.45%±8.21%, 51.48%±9.77% vs 30.70%±12.27%, t value was -8.126,-5.264, respectively, all P<0.05), which indicated that with the increase of the inspiratory flow rate, the deposition hotspot moved forward. Compared with the wet Artemisia pollen, the deposition rate of the dry pollen in nasal vestibule and nasal septum decreased significantly (16.55%±4.33% vs 27.45%±8.21%, 7.09%±3.69% vs 30.70%±12.27%, t value was 8.669, 9.173, respectively, all P<0.05). The escape rate at outlet increased from 17.00%±9.57% to 43.48%±13.43% (t=-9.282, P<0.05). Conclusions The deposition of Artemisia pollen in nasal cavity is highly concentrated. The inhalation velocity and the dry-wet degree of pollen are the main determinants of the deposition site.