Objective To prepare human anti-postsynaptic neurotoxin monoclonal antibody from phage antibody library using recombined postsynaptic short-chain neurotoxins ofLapemis curtus.Methods The three postsynaptic neurotoxins were expressed inEscherichia coli and phage antibodies against neurotoxins were screened. The obtained scFvs were further constructed to full antibodies. The antigen binding ability, biochemical and pharmacokinetic characteristics of the depurated antibodies were evaluated, and the anti-toxin effects of the antibody drugs were verifiedin vivo.Results Two positive scFvs with specific binding ability to all the three neurotoxins were obtained after 4 rounds of panning, and then the full antibodies were generated, expressed and purified. Antibody binding specificity was further confirmed. Pharmacokinetics of these two antibodies, SM-SD-911 and SM-SD-861 were similar to a conventional IgG molecule. SM-SD-911 and SM-SD-861 also showed strong antitoxin effectin vivo. Conclusionfull human anti-postsynaptic neurotoxin antibody has been successfully obtained by using recombinant neurotoxin technology and a large phage antibody library which may achieve clinical efficacy in navy medical applications.

Humans ; Liver Neoplasms ; diagnosis ; diagnostic imaging ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; Ultrasonography

Objective To investigate the difference in infarction characteristics between large artery atherosclerosis and cardioembolism acute ischemic stroke (AIS). Methods A retrospective study was done on 99 AIS patients, who were admitted to Emergency Room of our hospital and underwent multi-modal computed tomography (CT) after admission and before treatment. Forty-six of 99 AIS patients had large artery atherosclerosis and 53 had cardioembolism. The NIHSS score and GCS score on admission, infraction core and ischemic penumbra volumes and the volume difference, and vascular occlusion rates of posterior circulation and large artery were compared between the two groups. Results Compared with the cardioembolism group, the NHISS score was significantly lower and the GCS score was significantly higher in the large artery atherosclerosis group (9.5 [2.0, 16.0] vs 15.0 [6.0, 24.0], Z=2.31, P<0.001; 13.52±2.69 vs 11.60±3.31, t=1.04, P=0.002). The volumes of infarction core and ischemic penumbra in the cardioembolism group were 1 (0, 22) mL and 64 (30, 126) mL, respectively, and were both significantly larger than those in the large artery atherosclerosis group (0 [0, 1] mL and 10 [0, 70] mL; Z=3.85 and 3.43, both P<0.01). However, the volume difference of ischemic penumbra and infraction core was not significantly different between the cardioembolism and large artery atherosclerosis groups (46 [4, 103] mL vs 10 [0, 64] mL, Z=1.92, P>0.05). The large artery occlusion rate and posterior circulation occlusion rate were both significantly different between the large artery atherosclerosis and cardioembolism groups (30.43% [14/46] vs 50.94% [27/53] and 36.96% [17/46] vs 9.43% [5/53]; χ2=11.82 and 6.77, both P<0.001). Conclusion The clinical symptoms, cerebral changes and intracranial large artery changes are different in AIS patients with large artery atherosclerosis and cardioembolism. Etiology evaluation based on clinical features and multi-modal CT examination can help to accurately assess the ischemic state of AIS patients.

Ischemia/reperfusion injury (IRI) is a common clinical pathophysiological process characterized by ischemia and hypoxia. Hypoxia-inducible factors (HIFs) are a group of transcription factors vital to cell responding and adapting to hypoxia environment. Hypoxia can activate HIF, thus enhancing the tolerance of cells to hypoxia. The role of HIF in IRI has become a research focus of many scientists. Elucidating the related mechanism can not only help to reduce IRI, but also lay a basis for further studying the role of HIF in other pathophysiological processes. In this paper, we reviewed the structure, function of HIF and the specific role and related mechanisms of HIF in IRI.

To discuss the clinical value of diluted contrast enhanced Dyna CT in evaluating direct carotid-cavernous fistula(DCCF). Methods The clinical data of 16 patients with traumatic and solo fistulous DCCF were retrospectively studied. The images by 3D rotatory digital subtraction angiography (3D-DSA) and diluted contrast enhanced Dyna CT were used for comparison and analysis of their values for diagnosis of DCCF. The comparison items included information on the orificium fistulae, the retrograde leptomeningeal venous drainage (RLVD), the draining veins and the compartment of the cavernous sinus. Results Compared with 3D rotatory DSA, Dyna CT demonstrated 21 more findings in 15 patients (93.75%), including the detection of the orificium fistulae (n=8), the RLVD (n=2), the draining veins (n=2), and compartment of the cavernous sinus (n=9), with significant difference found between Dyna CT and 3D-DSA in revealing the orificium fistulae and compartment of the cavernous sinus (P<0.05), while not in revealing RLVD and the draining veins. Conclusion Compared with 3D-DSA, Dyna CT can more effectively demonstrate the orificium fistulae and compartment of the cavernous sinus of DCCF, which may benefit the clinical diagnosis and treatment of DCCF.

Objective: To test the hypothesis that acute phase reactants, such as alpha 1-antitrypsin and alpha 1-acid glycoprotein, could protect mammalian cells from further damage.Methods: Human dermal fibroblasts (5 × 104) were cultured with DMEM plus 10％ FBS at 37℃ in a 5％ CO2incubator. Different doses of LPS (lipopolysaccharide) and/or acute phase reactants were added. After 24 hours, the cultured supernatant was aspirated, the cells were washed, fixed and stained by methylene blue. The unbound stain was washed off. The stained cells were solubilized in 0.1 mi of 1％ Triton X-100. The absorbance of each well was measured using an ELISA spectrophotometer. The concentration of LPS which decreased the absorbance to 70％ of the control LPS-free ) cultures was defined as LD30.Results: In order to achieve LD30 in the presence of acute phase proteins, it was necessary to alter the LPS concentrations. The LD30 of LPS treated with 0, 0.5, 2, 10mg/ml antitrypsin and 0, 0.5, 2, 10 mg/ml glycoprotein was 5.4, 6.5, 7.6, 14.2 mg/ml and 5.2, 5.9, 6.9, 10.5mg/ml, respectively. Statistically, with the treatment of more than 2 mg/ml antitrypsin or glycoprotein, LD30increased significantly.Conclusions: Our data show that fibroblasts are susceptible to the direct toxicity of LPS. Alpha 1-antitrypsin and alpha 1-acid glycoprotein can reduce the toxicity and/or increase the tolerance of mammalian cells to LPS.

Research into the rational delivery and targeting of pharmaceutical, therapeutic, and diagnostic agents is at the forefront of projects in nanomedicine with the launch of ‘precision medicine’, and into the era of ‘precise’ targeted nano drug delivery system design. According to the lesion feature of disease endangering human health, it is one of the important strategies to design nano drug delivery system that targets each of the lesions which could change the distribution of drugs in the body, specifically increasing the concentration of drugs in the target sites and reducing the concentration of non-target sites, so as to enhance the efficacy, reduce adverse reactions and achieve precise nano-targeted treatment of diseases.at last. This article introduces the design principle and latest research progress of drug passive and active nano targeting delivery of drugs based on local microenvironment characteristics of lesions in tumors, atherosclerosis, inflammatory diseases in recent years, aiming to provide reference and basis for the design of more nano-targeted drug delivery systems for tumors and other diseases.

OBJECTIVETo introduce a safe and specific approach of (13)C magnetic resonance spectrum ((13)C MRS) spectroscopy and investigate the alterations in hepatic anabolism.

METHODSRelative anaplerotic, pyruvate recycling and gluconeogenic fluxes were measured by (13)C MRS isotopomer analysis of blood glucose from rats with 40% body surface area burn injury, and from rats exposed to sham injury. A short chain fatty acid, [U (13)C] propionate which was avidly extracted by the liver, was infused intravenously to deliver (13)C into the citric acid cycle. Proton-decoupled (13)C MRS of deproteinized plasma or extracts of the freeze-clamped liver were used to determine the distribution of (13)C in blood or hepatic glucose.

RESULTSThere was no difference in the multiplets detected in the glucose carbon-2 anomer from blood or liver after 45 or 60 minutes of the infusion of the propionate, indicating that steady-state isotopic conditions were achieved. Gluconeogenesis relative to citric acid cycle flux was not altered by burn injury; in both sham and burn groups the rate of glucose production was about equal to flux through citrate synthase. In the sham group of animals, the rate of entry of carbon skeletons into the citric acid cycle was about 4 times than that in the burn group. Similarly, flux through pyruvate kinase (again relative to citrate synthase) was significantly increased after the burn injury.

CONCLUSIONSSince results from analysis of the blood glucose are the same as that of the hepatic glucose, (13)C distribution in the glucose and hepatic metabolism can be assessed based on the (13)C MRS analysis of the blood glucose.

Animals ; Blood Glucose ; analysis ; Burns ; complications ; Carbon Isotopes ; Citric Acid Cycle ; physiology ; Disease Models, Animal ; Gluconeogenesis ; physiology ; Liver Diseases ; etiology ; pathology ; Liver Function Tests ; Magnetic Resonance Spectroscopy ; methods ; Male ; Probability ; Radiographic Image Enhancement ; Rats ; Rats, Sprague-Dawley ; Reference Values ; Sensitivity and Specificity

Prostate cancer (PCa) risk calculators (RCs) with prostate-specific antigen (PSA) and other risk factors can greatly improve the accurate prediction of potential risk of PCa compared to PSA. The European Randomized Study of Screening for PCa Risk Calculator (ERSPC-RC) and the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) are developed on the Western population. However, the Western RCs showed limited diagnostic efficacy in the Eastern Asian population, mainly due to racial differences between the two populations. We aimed to review the application of Western RCs and Eastern Asian RCs in Eastern Asian cohorts and to identify the characteristics and efficacy of these RCs.
Aged ; Early Detection of Cancer ; Asia, Eastern ; Humans ; Male ; Middle Aged ; Models, Theoretical ; Prostate-Specific Antigen/blood* ; Prostatic Neoplasms/diagnosis* ; Risk Assessment ; Risk Factors

Esophageal cancer is a common malignant tumor of the upper gastrointestinal tract. Early symptoms of the disease are inconspicuous and the disease is often diagnosed at a later stage, leading to higher morbidity and mortality. Esophageal cancer morbidity and mortality in both genders ranks among the top 10 most common cancers. Early detection and early treatment are effective means to reduce the incidence and mortality of esophageal cancer. Tumor markers play an important role in early diagnosis, treatment monitoring and prognosis evaluation of esophageal cancer. This paper reviews the clinical application of tumor markers related to esophageal cancer and the exploration and application progress of new tumor markers for esophageal cancer.