Objective To evaluate the immunogenicity of an immune complexed hepatitis B vac-cine ( HBsAg-HBIG immune complexes , IC) in mouse and cynomolgus monkeys by using recombinant hepa-titis B vaccine ( Saccharomyces cerevisiae, HBsAg) as the control .Methods BALB/c mice were vaccinated with single dose of IC and single dose of HBsAg respectively and then serum samples were collected at differ -ent time points for the detection of dynamic anti-HBs by using ELISA .The serum anti-HBs titers in BALB/c mice vaccinated with different immunization strategies were also analyzed .ELISPOT assay was performed to detect the numbers of IFN-γSFC and IFN-γpositive rate in splenocytes of BALB/c mice intramuscularly im-munized with IC, HBsAg or standard hepatitis B vaccine at 5μg/mouse.ED50 was measured to evaluate the stability of IC.Twelve cynomolgus monkeys were equally divided into two groups and immunized with high dose (100 μg) and low dose (20 μg) of IC respectively and then , serum anti-HBs levels at different time points were detected .Results The serum anti-HBs titers in IC immunized group at different time points were higher than those immunized with HBsAg .Moreover, the anti-HBs titer induced by two doses of IC reached a level comparable to that elicited by three doses of HBsAg .ELISPOT assay showed that both the numbers of IFN-γSFC and IFN-γpositive rate were the highest in IC immunized group as compared with those immunized with HBsAg and standard hepatitis B vaccine .IC had a lower ED50 than HBsAg, indicating a good long term stability .Cynomolgus monkeys immunized with high or low dose of IC produced high levels of anti-HBs titer during a long time period .Conclusion IC has a higher immunogenicity inducing both hu-moral immunity and cellular immunity as compared with HBsAg or standard hepatitis B vaccine .

OBJECTIVE:To optimize the formulation and preparation technology of Propylthiouracil(PTU)solid lipid nanopar-ticles(PTU-SLN)and to evaluate the quality of PLN-SLN. METHODS:PTU-SLN was prepared by emulsion ultrasound dispersing method. The formulation of PTU-SLN was optimized by orthogonal design with the entrapment efficacy and particle size as index, using the amount of lipid material,soybean lecithin and poloxamer 188 and ultrasonic time as factors. The quality of prepared nanoparticles was evaluated with particle size,Zeta potential,entrapment efficiency,stability and in vitro drug release rate as in-dex. RESULTS:The optimal formulation and technology was as follows as lipid material 0.6 g,soybean lecithin 1.0 g,poloxamer 188 0.8 g,ultrasonic time 10 min. The obtained PTU-SLN was round and smooth in appearance and distributed evenly in particle size with average particle size of 93.5 nm,Zeta potential of -30.8 mV and average entrapment efficiency of 74.9%. Prepared nanoparticles had no significant change after placing for 15 d at 4 ℃. Accumulative release rate of PTU-SLN was 56.1% at 4 hour in vitro and reached 98.4% at 24 hour. CONCLUSIONS:PTU-SLN is prepared successfully and reasonable in technology,and can reach sustained-release effects.

Child ; Electrocardiography ; Humans ; Male ; Ventricular Fibrillation ; physiopathology

Cholangiocarcinoma is a malignant tumor originating from the bile duct epithelium, with the increasing incidence year by year. Its early symptoms are atypical and the diagnosis rate is low. Most of the patients are already in advanced stage when they are diagnosed, losing the best surgery period. Currently, the conservative treatments for unresectable extrahepatic cholangiocarcinoma include stent placement, radiofrequency ablation, radiotherapy and chemotherapy, targeted and immunotherapy and other systemic treatments. But due to the high malignancy of biliary tract tumors, the tendency to develop drug resistance and the limited population benefited from the emerging treatment modalities, we urgently need to explore new treatment strategies to break this bottleneck. As a new treatment for cholangiocarcinoma, photodynamic therapy has attracted much attention for its clinical application and therapeutic effects. In this paper, we summarize the principles of photodynamic therapy, the combination of photodynamic and other therapeutic modalities, especially the combination of photodynamic with emerging immune and targeted therapies, and describe the current hotspot directions of photodynamic therapy research at home and abroad to provide reference for clinical treatment and research.

Objective To investigate the pharmaceutical care and the key points of drug intervention for a patient with cancer pain treatment provided by clinical pharmacists.Methods Clinical pharmacists took part in the therapy of a cancer pain patient with unknown primary,performed pain assessment,adjusted the drugs for pain control status together with clinicians.In addition,clinical pharmacists closely monitored the adverse reactions of patient induced by analgesic drugs,provided pharmaceutical suggestion for patient's constipation,established suitable treatment scheme.Results and Conclusion For patients with cancer pain,the pain controlling and the prevention of adverse reaction from opioids are very important,clinical pharmacists can help physicians serving patients better as to improve the quality of life for patients by taking part in clinical work and providing treatment suggestions from the perspective of pharmaceutical.

Objective To clone and express the HIV-1B gp120 genes isolated at different organizations from a patient died of AIDS dementia complex (ADC) in eukaryotic cells.Methods Using the genomic DNA isolated from peripheral lymphnodes,choroid plexus and occipital white matter from a patient died of ADC as the template,HIV-1B gp120 gene was amplified with PCR.After sequenced,HIVIB gp120 was inserted into pcDNA3.1 ( + ) and recombinant expressing vector gp120/pcDNA3.1 ( + ) was constructed succeffuly confirming with sequencing. Then expressing vector was transfected into eukaryotic cells U87 using liposome transfection and expression of HIV-1B gp120 gene was assayed with indirect immunofluorescence.Results HIV-I B gp120 genes isolated from peripheral lymphnodes,choroid plexus and occipital white matter of the ADC patient were successfully cloned and recombinant expressing vector gp120/pcDNA3.i ( + ) could express envelope glycoprotein HIV-1B gp120 in U87 cells.Conclusion All the HIV-1B gp120 gene isolated at the different organizations of the same ADC patient could express in U87 cells,which may supply a valuable basis for studying the neurotoxicity and neurotoxic mechanism of HIV-1 gp120 protein.

Background: Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation (c.5302G>C) of AGRN in a Chinese CMS pedigree. Methods: We performed a detailed clinical assessment of a Chinese family with three affected members. We screened for pathogenic mutations using a disease?related gene panel containing 519 genes associated with genetic myopathy (including 17 CMS genes). Results: In the family, the proband showed limb?girdle pattern of weakness with sparing of ocular, facial, bulbar, and respiratory muscles. Repetitive nerve stimulation showed a clear decrement of the compound muscle action potentials at 3 Hz only. Pathological analysis of the left tibialis anterior muscle showed predominance of type I fiber and the presence of scattered small angular fibers. The proband's two elder sisters shared a similar but more severe phenotype. By gene analysis, the same novel homozygous mutation (c.5302G>C, p.A1768P) of AGRN was identified in all three affected members, whereas the same heterozygous mutation was found in both parents, revealing an autosomal recessive transmission pattern. All patients showed beneficial responses to adrenergic agonists. Conclusions: This study reports a Chinese pedigree in which all three children carried the same novel AGRN mutation have CMS only affecting limb?girdle muscle. These findings might expand the spectrum of mutation in AGRN and enrich the phenotype of CMS.

Objective To analyze the immunostimulatory effects of cyclic dinucleotides ( CDN) on immune responses to a nasal spray influenza split virus vaccine and to evaluate its potential as a mucosal ad-juvant. Methods A H1N1 influenza split virus vaccine combined with different CDN was used for mouse immunization. Each mouse was intranasally immunized twice with 4. 5μg of hemagglutinin (HA) and 10μg of CDN with an interval of 21 d. Titers of hemagglutination inhibition ( HI) antibodies in serum, secretory IgA ( sIgA) in bronchoalveolar lavage fluid and IgG in serum were detected 21 d after the last immunization. Immunostimulatory activities of different CDN were compared. Effects of cyclic di-GMP ( c-di-GMP) and ch-itosan (CSN) on the immunogenicity of H1N1 and H7N9 influenza split vaccines were analyzed and com-pared. H1N1 influenza split vaccine combined with c-di-GMP or CSN was used to immunize mice. Three weeks after the last immunization, these mice were challenged with 10 times the median lethal dose ( LD50 ) of A/Puerto Rico/8/34 (H1N1) influenza virus. Survival rates of the mice were observed for 14 d. Results All three CDN induced high levels of HI antibodies and IgG in serum and sIgA in BALF. HI antibody sero-conversion rates were also higher than those of the control groups. c-di-GMP was superior to CSN in enhan-cing the immunogenicity of H1N1 and H7N9 antigens as higher titers of HI antibodies in serum and sIgA in BALF were induced. Conclusions CDN could enhance the immunogenicity of influenza antigens with better efficacy than CSN adjuvant.

Chemotherapy resistance is the main cause of poor prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC). Pyroptosis is one of the anti-tumor mechanisms by chemotherapy drugs. Studies have shown that DEP-domain containing mTOR-interacting protein (DEPTOR) is correlated with sorafenib and gefitnib resistance, which is discovered as a naturally negative regulator of mammalian/mechanistic target of rapamicin (mTOR). In this study, DEPTOR knockdown (shDEPTOR) lentivirus was used to establish the stable DEPTOR knockdown ESCC cell lines. The results showed that knockdown of DEPTOR reduced chemosensitivity to cisplatin in ESCC cells in vitro. The lower expression of DEPTOR caused less extensive morphological characteristics of pyroptosis than that was observed in sh-con cells with the treatment of cisplain. Further studies showed that knockdown of DEPTOR induced downregulation of Caspase-1 expression and reduction of Caspase-1 activation, thereby inhibiting the activation of the classical pathway of pyroptosis. This paper demonstrates that DEPTOR can improve cisplatin chemosensitivity in ESCC cells via inducing Caspase-1-mediated pyroptosis.