Research progress of EGFRvIII targeted immunotherapy in the treatment of glioblastoma / 药学学报

Glioblastoma (GBM) is the most common primary brain tumor, which is prone to recurrence and metastasis with poor prognosis. In recent years, immunotherapy has prolonged the survival of patients with GBM, providing a new option for the treatment of GBM. Target selection is very important for immunotherapy. Epidermal growth factor receptor variant III (EGFRvIII) is highly expressed on the surface of GBM cells in some patients, and EGFRvIII was not expressed in normal tissues. EGFRvIII are pivotal for the occurrence and progression of GBM, various targeted therapy including immunotherapy is promising to improve the efficacy of GBM. Currently, there are various approaches to target EGFRvIII, including humanized monoclonal antibodies, adoptive cell therapies and therapeutic vaccines. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM.

Bone morphogenetic proteins and inner ear development / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-β superfamily, and they play important roles in the development of numerous organs, including the inner ear. The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance. Here, we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.

Antibody-drug conjugates:design and clinical progress / 药学学报

Antibody-drug conjugates, constructed with monoclonal antibodies, linker and cytotoxins, have distinctive advantages over chemotherapy drugs and antibody drugs in cancer therapy. In this review, the strategy of developing ADCs, and the important progress in past decade are well summarized. The representative ADCs in the pipeline are introduced and characterized with their new features. While, perspective for future directions of ADCs is proposed.

Effects of high glucose on expression of OPG and RANKL in rat aortic vascular smooth muscle cells

OBJECTIVE@#To explore effect of high glucose on expression of osteoprotegerin (OPG) and receptor activator of NF- κ B ligand (RANKE) in rat aortic vascular smooth muscle cells.@*METHODS@#SD rats were intraperitoneally injected with streptozotocin, OPG and RANKL expression in rat thoracic aortas were detected by immunohistochemical staining. In cultured vascular smooth muscle cells (VSMCs) (A7r5), qRT-PCR and Western blot analysis were used to examine the mRNA and protein levels of OPG and RANKL.@*RESULTS@#Our results demonstrated that OPG expression was increased in hyperglycemic rat aortic VSMCs, while RANKL expression was decreased. Besides, in vitro experiments high glucose induced OPG expression, but depressed RANKL expression by dose- and time-dependent manner in cultured A7r5.@*CONCLUSIONS@#Our findings suggested that high glucose could promote the expression of OPG, and inhibit the expression of RANKL in VSMCs, which may be partly be the molecular mechanism of diabetic vascular calcification.

Effects of high glucose on expression of OPG and RANKL in rat aortic vascular smooth muscle cells

Objective: To explore effect of high glucose on expression of osteoprotegerin (OPG) and receptor activator of NF- κ B ligand (RANKE) in rat aortic vascular smooth muscle cells. Methods: SD rats were intraperitoneally injected with streptozotocin, OPG and RANKL expression in rat thoracic aortas were detected by immunohistochemical staining. In cultured vascular smooth muscle cells (VSMCs) (A7r5), qRT-PCR and Western blot analysis were used to examine the mRNA and protein levels of OPG and RANKL. Results: Our results demonstrated that OPG expression was increased in hyperglycemic rat aortic VSMCs, while RANKL expression was decreased. Besides, in vitro experiments high glucose induced OPG expression, but depressed RANKL expression by dose- and time-dependent manner in cultured A7r5. Conclusions: Our findings suggested that high glucose could promote the expression of OPG, and inhibit the expression of RANKL in VSMCs, which may be partly be the molecular mechanism of diabetic vascular calcification.

Artificial antigen-presenting cells plus IL-15 and IL-21 efficiently induce melanoma-specific cytotoxic CD8+ CD28+ T lymphocyte responses

OBJECTIVE@#To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8(+) CD28(+) cytotoxic T lymphocyte (CTL) responses.@*METHODS@#Cell-sized Dynabeads® M-450 Epoxy beads coated with H-2K(b): Ig-TRP2180-188 and anti-CD28 antibody were used as artificial antigen-presenting cells (aAPCs) to induce melanoma-specific CD8(+)CD28(+) CTL responses with the help of IL-21 and IL-15. Dimer staining, proliferation, ELISPOT, and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs.@*RESULTS@#Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8(+)CD28(+)CTLs. Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- γ under the stimulation of H-2K(b): Ig-TRP2-aAPCs, IL-15, and IL-21. In addition, cytotoxicity experiments showed that induced CTLs have specific killing activity of target cells.@*CONCLUSIONS@#The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8(+) CD28(+) CTLs against the melanoma. Our study provides evidence for a novel adoptive immunotherapy against tumors.

Comparison of direct immune-fluorescent assay and real-time quantitative PCR in detecting the Hantavirus / 中华预防医学杂志

<p><b>OBJECTIVE</b>To compare the differences between the direct immuno-fluorescent assay (DFA) and real-time quantitative PCR in detecting the Hantavirus (HV) in rat lungs.</p><p><b>METHODS</b>From April to October in 2012, a total of 479 rats were caught by mouse-trap in residential or wild areas in Huxian, Jingyang, and Meixian of Shaanxi province, where haemorrhagic fever with renal syndrome (HFRS) was highly prevalent. The rats were dissected to take the two lungs, one was frozen and applied immuno-fluorescent assay to detect HV antigen while the other one was extracted its RNA and detected HV nucleic acid by real-time quantitative PCR. Then we compared the positive rate of the two methods.</p><p><b>RESULTS</b>Out of the 479 rats, 105 were caught from residential areas and the other 374 were caught from wild areas. Among the 105 rats caught from residential areas, no HV were detected out neither by DFA nor by real-time quantitative PCR. Among the 374 wild rats, 13.1% (49/374) were detected HV positive by DFA and 14.7% (55/374) were detected HV positive by real-time quantitative PCR. The difference showed no statistical significance (χ(2) = 0.402, P = 0.526). When detecting each lung sample, the HV positive rate was 10.2% (49/479) under the detection by DFA while the HV positive rate was 11.5% (55/479) under the detection by real-time quantitative PCR. The difference had no statistical significance (χ(2) = 1.286, P = 0.257) and the consistency coefficient was 68.2% under the paired chi-square test analysis, which showed high consistency (u = 11.759, P < 0.05). The sensitivity of real-time quantitative PCR to detect HV was 77.6% (38/49) comparing with DFA as standard, and the specificity was 96.1% (413/430). Out of the 9 suspected HV positive sample detected by DFA, 6 were confirmed positive by real-time quantitative PCR and 3 were denied.</p><p><b>CONCLUSION</b>Compared with the DFA, real-time quantitative PCR could also be used to detect the infection of HV in rats, and the result might be more stable.</p>

Long term epidemiological effects of vaccination on hemorrhagical fever with renal syndrome (HFRS) in Shaanxi provincial HFRS epidemic areas / 中华流行病学杂志

Objective To evaluate the protective rate and the variation of HFRS-IgG on hemorrhagical fever with renal syndrome (HFRS) vaccine.Methods Cluster,random sampling and cross-sectional study were used to assess the protective rate of HFRS vaccination.Level of HFRS-IgG was detected with ELISA in epidemic and non-epidemic areas of HFRS.Results Curve equation was obtained as Yprocective rate=(0.863+0.283/Xvaccination term) × 100％ by protective rate with vaccination term.Protective rates showed a reducing trend,90％ after 7-8 years of vaccination,88％ after 10 years,and 94％ on average.Absorbance (A) value of HFRS-IgG was 4 times higher in persons with vaccination than those without,in the epidemic area.Higher antibody level could be obtained after primary vaccination,but the level of antibody had a 50％ reduction after 5-10 years of vaccination,and a 60％ reduction after 10 years of vaccination.Conclusion HFRS antibody had a 50％ reduction after 5-10 years of vaccination.The protective rate of HFRS vaccination had a 90％ loss,after 7-8 years of vaccination.Booster dose was necessary after 7 years of vaccination.

Three-dimensional morphological characteristics measurement of ankle joint based on computed tomography image post-processing / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As precise positioning of ankle radiography is not possible, quantitative measurement of all syndesmotic parameters on repeated ankle X-ray films may be of little value. The purpose of this study was to provide a set of scientific and objective evaluation criteria for assessing the quality of ankle fracture reduction accurately and reliably by an intelligent combining three-dimensional (3-D) computed tomography (CT) measurement model.</p><p><b>METHODS</b>From June 2008 to March 2011, all the thin-slice CT images of 100 cases (50 males and 50 females) with normal ankle joint scanned by 16-slice spiral CT were collected. Two-dimensional (2-D) and 3-D images of ankle joints were generated by using multiple planar reconstruction (MPR) and surface shaded display (SSD) respectively. The relevant parameters about bone structures and their relationship were measured and analyzed based on 3-D topological narrow division technique and 3-D measurement techniques combining essential elements of point, line and surface.</p><p><b>RESULTS</b>In this study, the mean distance from lateral malleolus tip to talocrural articular surface, the tip of medial malleolus anterior colliculus to talocrural articular surface and lateral malleolus tip to the tip of medial malleolus anterior colliculus were (22.83 ± 1.12) mm, (12.84 ± 1.09) mm, and (61.18 ± 2.03) mm respectively in male group, and (20.16 ± 1.00) mm, (10.30 ± 1.05) mm and (53.00 ± 1.40) mm respectively in female group. The above three parameters were correlated with gender, height and weight (P < 0.05). However, the mean perpendicular distance from lateral malleolus tip to the plane through the tip of medial malleolus anterior colliculus, the talocrural angle, later clear space, medial clear space, and the superior clear space were (9.93 ± 0.29) mm, (10.01 ± 0.38)°, (1.94 ± 0.16) mm, (2.78 ± 0.19) mm, and (3.14 ± 0.15) mm respectively in 100 cases, were not significance correlated with gender, height and weight (P > 0.05).</p><p><b>CONCLUSIONS</b>This study could provide a certain amount of relevant data for the standard of injured ankle anatomical reduction and the second surgery planning after malunion. The methods of measurement are reliable, reproducible, and easy to apply in practice.</p>

Prevalence and risk factors of peri-procedure electrical storm in acute myocardial infarction patients underwent emergency percutaneous coronary intervention / 中华心血管病杂志

<p><b>OBJECTIVE</b>To determine the prevalence and to identify risk factors of peri-procedure electrical storm (ES) in patients with acute myocardial infarction (AMI) underwent emergency percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>The clinical data of 228 AMI patients underwent emergency PCI were retrospectively analyzed and patients were divided into ES group (n = 39) and non-ES (n = 189) group. ES was referred to spontaneous ventricular tachycardia or ventricular fibrillation occurring twice or more within 24 h and requiring emergency treatment including anti-arrhythmic medicine and/or cardioversion or defibrillation.</p><p><b>RESULTS</b>ES was diagnosed in 39 out of 228 patients (17.1%) during peri-procedure stage. The incidence of ES in patients with various infarct related arteries (IRA) was as follows: 55.6% with left main artery (LM), 23.7% with right coronary artery (RCA), 12.4% with anterior descending branch (LAD) and 0 with left circumflex artery (LCX). Older age, lager diameter of IRA, higher concentration of CK-MB and cTnT, higher incidence of reperfusion arrhythmia (RA), lower grade of TIMI after PCI and higher mortality were associated with increased risks of ES (The P value was 0.043, 0.012, 0.036, 0.018, 0.001, 0.049, respectively). Gender, systolic pressure, diastolic pressure, random blood glucose level, white blood count and concentration of hs-CRP were similar between ES and non-ES patients. Logistic analysis showed that the diameter of IRA (OR 2.381, 95%CI 1.127-5.028, P = 0.023), TIMI grade of IRA after PCI (OR 4.744, 95% CI 1.773-12.691, P = 0.002) and RA (OR 12.680, 95% CI 4.360-36.879, P = 0.000) were the independent risk factors of per-procedure ES in AMI patients underwent emergency PCI.</p><p><b>CONCLUSIONS</b>The AMI patients with LM as IRA had the highest incidence of ES during emergency PCI and the diameter of IRA, TIMI grade of IRA after PCI and RA were independent risk factors for the development of ES during peri-PCI stage.</p>

Anti-proliferation of human cervical cancer HeLa cell line by fascaplysin through apoptosis induction / 药学学报

This study is to investigate the effect of fascaplysin on human cervical cancer cells (HeLa) in order to provide insights into the mechanisms of growth suppression involved in fascaplysin-mediated apoptosis. Cytotoxic activity of fascaplysin on HeLa cells was determined using MTT assay, cell cycle analysis, and apoptosis (Annexin V-FITC and PI double staining) studies. The role of the molecules in cell cycle regulation and apoptosis was analyzed by Western blotting and flow cytometry. Fascaplysin markedly inhibited HeLa cells proliferation in a dose-dependent manner, however, did not provoke G1 phase arrest in HeLa cells with downregulation of CDK4, cyclin D1 and CDK4-specific Ser795 pRb phosphorylation. Furthermore, fascaplysin induced significantly apoptosis evidenced by sub-G1 peak and Annexin V-FITC and PI double staining. The molecular mechanism of fascaplysin-induced apoptosis was characterized with the activation of caspase-3, -8, and -9, truncation of Bid, release of cytochrome c into cytosol, and down-regulation of Bcl-2 level. Fascaplysin exhibits anti-proliferation effect towards human cervical cancer HeLa cells through induction of apoptosis via extrinsic death pathway and mitochondrial pathway, but not arresting cell cycle progression at G1 phase. All together, these data sustain our contention that fascaplysin has anticancer properties and merits further investigation as a potential therapeutic agent.