Objective To investigate the effect of erythropoietin (EPO) on the expression of MMP-2 in hippocampus of neonatal rats after hypoxic-ischemic brain damage (HIBD), and the mechanism of its neuroprotective effect. Methods Neonatal Sprague-Dawley rats of 7 days old were randomly divided into three groups (n?=?48 in each group): sham-operated group, HIBD group and EPO treated group, then each group was further divided into four subgroups (n?=?12) based on different time points following the injection of medication ( 6 h, 24 h, 3 d, 7 d). The expression of MMP-2 in hippocampus was determined by immunohistochemistry and real-time lfuorescent quantitative PCR method. Results Immunohistochemistry: MMP-2 has a small amount of expression in the hippocampus of the sham-operated group, and at each time point, there is no statistically signiifcant difference (P?>?0.05);The expression of MMP-2 in HIBD group and EPO group all show a trend of increase, and peaked at 7 d, the differences between each time point in two groups are statistically signiifcant (P??0.05). Gene expression in HIBD group at 24 h and 7 d points showed twin peaks, and the peak is higher at the 7 d point, but without difference (P?>?0.05). MMP-2 expression of EPO group presents a trend of increase, and differences are signiifcant between each time point (P?

Photodynamic therapy (PDT) has attracted wide attention due to its unique advantages such as minimal invasiveness, high efficiency and high selectivity, and its ability to induce anti-tumor immune response. However, the treatment process is heavily dependent on the oxygen content of the treatment site, and the widespread oxygen deficiency in malignant tumors severely limits its efficacy. In addition, PDT-mediated oxygen depletion exacerbates tumor hypoxia, which further reduces its therapeutic effect. In recent years, many researches have been devoted to overcoming this problem. This paper summarized various strategies based on tumor hypoxic PDT in recent years, discussing the advantages and disadvantages of these strategies, and analyzing the main challenges and future directions of PDT in the treatment of tumors, so as to provide references for the in-depth study of photodynamic therapy of tumors.

Objective To assess the feasibility for the automated treatment planning verification system Mobius3D (M3D) to perform an independent 3D dose calculation in intensity-modulated radiotherapy (IMRT) for cervical cancer.Methods Twenty patients with cervical cancer were randomly selected.With treatment planning systems (Pinnacle,Version 9.2;Eclipse,Version 13.5),all IMRT plans were divided into 7 fields to meet the dosimetric goals.The optimized plans were exported to the M3D server.The percentage differences in the volume of region of interest (ROI) and the dose calculation of target volume and organ at risk (OAR) were evaluated for the two treatment planning systems,and theγ passing rate was used to assess the accuracy of M3D calculation.Results The difference in the volume of ROI for Pinnacle 9.2 to M3D was less than that for Eclipse 13.5 to M3D,with maximum differences of 0.22％±0.69％ and 3.5％±1.89％ for Pinnacle 9.2 and Eclipse 13.5,respectively.The differences in the dose calculation of target volume and OAR for the two treatment planning systems to M3D were within ± 1％.After recalculating by M3D,the dose difference between Pinnacle 9.2 and M3D was smaller than that between Eclipse 13.5 and M3D,but the mean differences were all within ±3％.The γ passing rates for target volume and OAR were more than 95％ on average.Conclusions The method of utilizing the automated treatment planning verification system to validate the accuracy of plans is convenient.It can be used as a secondary check tool to improve accuracy in IMRT dose calculation.

″Herb-Pairs″, also known as pair drugs, refers to a prescription consisted of two relatively fixed traditional Chinese medicine, is the most basic, most simple and most common form of medication prescription in traditional Chinese medicine compound compatibility. It is not a random combination of two herbs, nor is the simple accumulation of efficacy, but the simple and delicate experience of ancient Chinese medicine practitioners. As a bridge between single drug and prescriptions, it is the embodiment of the regular and dialectical connotation. Therefore, research on Herb-Pairs has always been the most basic and most important entry point for compound compatibility studies. However, the interaction between herbs and herbs is an effect with a downside as well as benefits. The beneficial herb-herb interaction in Herb-Pairs include mutual promotion, mutual enhancement, mutual restraint between two drugs and counteract toxicity of another drug. And the harmful herb- herb interaction in Herb- Pairs includes mutual inhibition and antagonism. All of these interactions areby means of affecting the metabolism of components to play a therapeutic effect. Using the pharmacokinetic-pharmacodynamic (PK-PD) binding model, the combination of drug metabolism and pharmacodynamics can further elucidate the influence on effect caused by drug concentration and metabolism, which can help elucidate the mechanism of drug action. Consequently, in this review, the herb-herb interactions in terms of pharmacokinetic were summarized to elucidate rule of TCM compatibility.

Objective To investigate the age-associated changes of ultrastructure,mRNA and protein expressions of H+-K+-ATPase in elderly gastric parietal cell. Methods Fifty patients with relative normal stomach without gastroduodenal diseases were enrolled,including younger group (aged 20-59 years,n=19) and elderly group (aged≥60 years,n=31).Furthermore,the elderly group was divided into 3 subgroups:60-69 years old (n =11 ),70-79 years old (n=10 ),above 80 years old (n =10).The ultrastructure of gastric parietal cell was observed under electron microscope.The expression of H+-K+-ATPase α subunit mRNA and H+-K+-ATPase β subunit protein were assessed by quantitative real-time PCR and Western-blot,respectively.The ageing-associated changes of all these data were respectively compared. Results No significant difference was showed in the morphology of gastric parietal cell and acid-secretion-associated organelles among all the groups.The average ratio Am to Ac (Am means the area of mitochondria,Ac means the area of cytoplasm) of gastric parietal cell and the average At to Ac ratio (At means the area of secretory canaliculi and tubulovesicular system )between younger group and elderly group had no significant difference[(48.4±7.5) ％ vs.(50.6±7.6) ％,t=-0.775,P=0.444; (13.8±4.1) ％ vs.(12.2±4.7) ％,t=0.984,P=0.332].Meanwhile,there were no distinctions in the expression of H+-K+ -ATPase α subunit mRNA and H+-K+-ATPase protein among all elderly subgroups(F=1.522,2.32,P=0.24,0.114).However,the mRNA expression of H+-K+-ATPase a subunit was higher in the elderly group than in the younger group(t=-3.682,P=0.001).Furthermore,the expression of H+ -K+ -ATPase protein in the elderly group was increased as compared with younger group(t=-3.389,P=0.004). Conclusions Acidsecretion-associated organelles of human gastric parietal cell have no degeneration and the expression of H + -K+-ATPase is in trend of increase with aging,indicating that healthy elderly people have the basis of ultrastructure and molecular biology to maintain well function of acid secretion.

Obesity is an established risk factor for endometrial cancer. Leptin, a secreted protein of the ob gene by white adipose tissue, plays an important role in the regulation of food intake and energy consumption in the brain and acts as a potential growth stimulator in normal and neoplastic cancer cells. However, a direct role for leptin in endometrial cancer has not been demonstrated. In the present study, the effect of leptin on the proliferation of Ishikawa endometrial cancer cells was investigated as well as the possible mechanism(s) underlying this action in endometrial cancers which express both short and long isoforms of leptin receptors. The expression of leptin receptor (ObRb) in Ishikawa cells was detected by RT-PCR and Western blotting. The cells after serum starvation, were treated by leptin with various concentrations (0, 10, 50, 100, 150 ng/mL) for different durations (6, 12, 24 h). The effect of leptin treatment on cell proliferation was examined by MTT assay. Meanwhile, inhibitory effect of Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) inhibitor AG490 or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on the proliferation of Ishikawa cells induced by leptin was also studied. Ishikawa cells were treated with 100 ng/mL leptin for various periods (0, 20, 40, 60 min), and the levels of STAT3 phosphorylation and ERK1/2 phosphorylation were examined by Western blotting. The results showed that leptin induced the phosphorylation of STAT3 and the activation of ERK1/2 in a time- and dose-dependent manner in the Ishikawa endometrial cancer cells. Blocking STAT3 phosphorylation with the inhibitor AG490, or blocking ERK1/2 activation by the specific ERK1/2 kinase inhibitor, PD98059, abolished leptin-induced proliferation of Ishikawa cells. In addition, leptin was found to potently induce the invasion of endometrial cancer cells in a Matrigel invasion assay. Leptin-stimulated invasion was effectively blocked by pharmacological inhibitors of STAT3 (AG490) and ERK1/2 kinase (PD98059). These results suggested that leptin promotes endometrial cancer growth and invasiveness by activating STAT3 and ERK1/2 signaling pathways and therefore blocking its action at the receptor level can be a rational therapeutic strategy.

Background Ostrich acellular corneal stroma possesses a similar constitution to human corneal stroma,so it is expected to become one of ideal biological corneal carriers.Objective This study was to investigate the immunogenicity of acellular stroma carrier of ostrich cornea and offer the information for the development of industrialization and clinical use of acellular stroma carrier of ostrich cornea.Methods Twenty fresh ostrich eyeballs and 20 porcine eyeballs were collected.Acellular corneal stroma carriers of ostriches and pigs were prepared using low temperature freezing joint enzyme digestion method and desiccant dehydration method and sterilized by cobalt-60 irradiation.The corneal stroma carriers were preserved using drying and dehydration method.Forty-five male BALB/c mice were randomly divided into the sham operation group,ostrich acellular corneal stroma group and porcine acellular corneal stroma group.Acellular corneal stroma carriers of ostriches and pigs(wet weight after rewatering was 10 mg/piece) were subcutaneously implanted to the back of BALB/c mice,respectively.Wound healing and inflammatory response on the operative site were observed,and phenotype and activating rate of CD4+,CD8+ and CD25+in peripheral blood of mice were dynamically detected 7,14 and 28 days after ectopically implantation of heterogeneous corneal stroma by immunofluorescence labeling and flow cytometry analysis.Results No swelling and exudation were seen in the skin of operative site of the mice with a good healing of wound after surgery.There were no significant differences in the activating rates of CD4+,CD8+ and CD25+ cells in the peripheral blood of mice among the sham operation group,the porcine acellular corneal stroma group and ostrich acellular corneal stroma group in the three time points after surgery(CD4+:F=0.74,P=0.50;F=0.39,P=0.05;F=3.46,P=0.58.CD8+:F=1.75,P=0.21 ;F=1.14,P=0.35;F=0.78,P=0.48.CD25+:F=0.52,P=0.61 ;F=3.53,P=0.62;F=2.42,P=0.13).Conclusions The ostrich acellular heterogeneous corneal stroma carrier possesses low immunogenicity.It is inferred that ostrich acellular corneal stroma carrier can be used in heterogeneous corneal transplantation.

Female ; Humans ; Middle Aged ; Neoplasm Metastasis ; pathology ; physiopathology ; Pituitary Gland ; pathology ; Pituitary Neoplasms ; pathology

Humans ; Minimally Invasive Surgical Procedures ; utilization

Objective To investigate the development strategy of novel T cell based vaccine against HCV infection.Methods BALB/c mice were primed with pSCK-based DNA vaccine and boosted with type 5 adenoviral vector-based vaccine, which expressed the structural proteins ( Core, E1 and E2) de-rived from a Chinese HCV patient (genotype 1b, Hebei strain).Enzyme linked immunospot assay (ELIS-POT) and intracellular cytokine staining ( ICS) were used to analyze the elicited antigen-specific immune re-sponses and the efficacy of cross-protection.Results Immunization of mice with the prime-boost vaccination strategy elicited stronger T cell immune responses against multiple HCV antigens than using the DNA vac-cines alone, especially the IFN-γ-secreting T cell responses against E1 protein as indicated by ELISPOT as-say.ICS data indicated that the prime-boost regimen elicited more TNF-α-producing CD4+and IFN-γ-produ-cing CD8+T cells against E1 protein and high levels of IFN-γ-producing CD4+and CD8+T cells against E2 protein in comparison with immunization with DNA vaccines.Moreover, the prime-boost vaccination was ca-pable of eliciting effective cross-protection in a surrogate challenge model based on a recombinant heterolo-gous HCV (JFH1, 2a) vaccinia virus.Conclusion The prime-boost vaccination using DNA and rAd5-based vaccine expressing HCV structural antigens induced significant cellular immune response and cross-protection in mice, suggesting the possibility of using it as a promising T cell based vaccine against HCV in-fection.