Analysis of teaching difficulties in the chapter of antigen in Medical Immunology and teaching strategy / 细胞与分子免疫学杂志

The concept of "ntigen"is a relative one. The narrow concept of it condenses the process of activation of adaptive immune response and re-recognition of the same antigen, revealing the protective mechanism of vaccines with great significance for research and development of vaccines. However, the narrow concept involves adaptive immune system members: B cells, T cells and their effector products, which is difficult for beginners to understand the inherent meaning. Meanwhile, antigen classification fully summarizes the immune response process, so a variety of classification approach increases the difficulty in learning. Our teaching team analyzes the difficulties of this chapter in depth, and we implements the strategy that takes antibody structure and function as the breakthrough point and simplified adaptive immune response process as the core in teaching. A mind map that includes the main contents of this chapter is made during the process, which promotes the effectiveness of classroom teaching greatly.

Distribution of monocyte subsets and their surface CD31 intensity are associated with disease course and severity of hemorrhagic fever with renal syndrome / 细胞与分子免疫学杂志

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14++CD16-), intermediated monocyte subsets (CD14++CD16+) and non-classical monocyte subsets (CD14+CD16++) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.

Traditional Chinese medicine used as anti-aging agent by targeting nuclear factor erythroid 2-related factor 2 signaling pathway / 生理学报

The imbalance of redox homeostasis is a major characteristic of aging and contributes to the pathogenesis of various aging-related diseases. As a regulatory hub of redox homeostasis, nuclear factor erythroid 2-related factor 2 (NRF2) can attenuate oxidative stress by activating the transcription of many antioxidant enzymes. China is the birthplace of traditional Chinese medicine (TCM) which has been wildly used as medicine for thousands of years. Recently, TCM as anti-aging medicine has attracted enormous attention. Focusing on the NRF2 signaling pathway, this paper summarizes the correlation between various anti-aging TCM and the NRF2 signaling, and discusses the common key mechanisms by which TCM slows the aging process by targeting the NRF2 signaling network.

Research progress on the role of monocytes in viral hemorrhagic fevers / 细胞与分子免疫学杂志

Monocytes are important target cells of various hemorrhagic fever viruses. In viral hemorrhagic fevers (VHFs), monocytes can be infected by viruses and produce different kinds of cytokines, which contribute to the antiviral immune response and participation in the immunopathogenesis of VHFs. During the pathogenesis of various VHFs (early stage), monocytes change in cell counting, subpopulation distribution and expression of surface molecules with an activated phenotype. Several hemorrhagic fever viruses can infect monocytes and induce immune response, which may play an important role in immunopathological injury. Monocytes and the cytokines they produce may interact with platelets and vascular endothelial cells, contributing to disease progression.

Efficacy of BMMSCs on aGVHD and Its Correlation with SerumInflammatory Cytokines in Pediatric Patients with Severe Refractory Acute Graft-Versus-Host Disease / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy of bone marrow mesenchymal stem cells (BMMSC) on children with refractory graft-versus-host disease (GVHD) and to judge the efficacy of BMMSC by dynamically monitoring the changes of cytokines in children with GVHD before and after infusion of BMMSC, so as to provide a theoretical basis for clarifying the mechanism of BMMSC.@*METHODS@#17 children with refractory aGVHD including 7 of grade II, 6 cases of grade III and 4 cases of grade IV after allo-HSCT were enrolled. All the children with aGVHD, who received routine immunosuppressive therapy, but the state of disease not improved, were treated with immunosuppressive drugs combined with BMMSC infusion. Study endpoints included safety of BMMSC infusion, response to BMMSC, and overall response of aGVHD. The serum levels of IL-2α, IL-6, IL-10, IL-8 and TNF-α in aGVHD patients were measured by chemiluminescence before infusion of BMMSCs and Day 7, Day 14 after infusion of BMMSCs.@*RESULTS@#The cumulative median dose of BMMSCs was 5.5 (3.4-11.1) × 10/kg for average of 3.7 times, and the median time of 16.5 (4-95) days for the first infusion of MSCs. In 17 cases of refractory GVHD, 14 responded to treatment, whereas 3 patients failed. The total effective rate was 82.4% and no adverse reactions occurred. Of the 14 survived cases (82.4%), the median follow-up time was 944 (559-1245) days from the first infusion of MSCs. The levels of TNF-α in children with grade II, III and IV GVHD before treatment were 9.5±4.3 pg/ml, 16.3±10.9 pg/ml and 35.8±21.2 pg/ml respectively. The difference between grade II and IV, III and IV was statistically significant (P<0.05). Compared with the ineffective group of BMMSC infusion, the serum TNF-αlevel in the BMMSCs treatment effective group was 10.8±5.6 pg/ml vs 40.6±14.8 pg/ml (t=-3.901, P<0.05) before treatment. In the effective group of BMMSCs infusion, IL-10 20±17.4 pg/ml of day 14 was significantly higher than that 7.3±3.1 pg/ml before the treatment (t=-2.850, P<0.05), while , the serum levels of IL-2α, IL-6, IL-8, TNF-α were not statistically significantly different (P＞0.05).@*CONCLUSION@#The infusion of BMMSC is safe and effective in the treatment of refractory GVHD in children. TNF-αlevel relates with the severity of GVHD. BMMSC may play an anti-GVHD role by up regulating the level of cytokine IL-10 in vivo.

AGE/RAGE regulates the epithelial-mesenchymal transition and stemness maintenance of colorectal cancer cells / 肿瘤

Objective: To explore the effects of advanced glycation end products (AGEs) on the epithelialmesenchymal transition (EMT) and stemness maintenance of colorectal cancer HCT116 cells and its possible mechanism. Methods: The abilities of proliferation, migration, invasion, clone formation and sphere formation of HCT116 cells after treatment with 200 μg/mL AGEs and 200 μg/mL AGEs in combination with 50 μmol/L phosphatidylinositol-3 kinase (PI3K)-specific inhibitor LY294002 were detected by CCK-8, wound-healing assay, Transwell chamber assay, clone formation assay and sphere formation assay, respectively. After treatment with 200 μg/ mL AGEs and 200 μg/mL AGEs in combination with 50 μmol/L LY294002, respectively, the ability of invasion and the proportion of CD133plus signsphered HCT116 cells as well as the expressions of CD133, matrix metalloproteinase-2 (MMP-2) and MMP-9 in sphered HCT116 cells were detected by Transwell chamber assay, FCM and Western blotting, respectively. The expressions of the receptor of advanced glycation end products (RAGE), E-cadherin, N-cadherin, vimentin, Snail, PI3K, phosphorylated PI3K (p-PI3K), protein kinase B1 (PKB1, Akt1) and phosphorylated Akt1 (p-Akt1) in sphered HCT116 cells after treatment with different concentrations of AGEs, 200 μg/mL AGEs and 200 μg/mL AGEs in combination with 50 μmol/L LY294002 respectively were detected by Western blotting. Results: The abilities of migration, invasion, clone formation and sphere formation of HCT116 cells after treatment with 200 μg/mL AGEs were improved (P < 0.01, P < 0.05, P < 0.01, P < 0.01, P < 0.05), and these effects were inhibited by 50 μmol/L LY294002 (P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.05). After treatment with AGEs, the ability of invasion and the proportion of CD133plus sign sphered HCT116 cells were increased (P < 0.01, P < 0.05), and the expression levels of CD133, MMP-2 and MMP-9 were up-regulated (all P < 0.05), whereas these effects were opposite by 50 μmol/L LY294002 (P < 0.01, P < 0.05, all P < 0.05). The expression level of RAGE in HCT116 cells after treatment with different concentrations of AGEs was up-regulated (P < 0.05). After treatment with 200 μg/mL AGEs, the expression levels of p-PI3K, p-Akt1, N-cadherin, vimentin and Snail proteins were up-regulated (all P < 0.05), whereas the expression level of E-cadherin protein was down-regulated (P < 0.05); but these effects were opposite by 50 μmol/L LY294002 (all P < 0.05). Conclusion: AGE activates the RAGE signal pathway and improves the abilities of proliferation, migration, invasion, clone formation and stemness maintenance of colorectal cancer HCT116 cells, and this mechanism may be related to EMT mediated by AGE/RAGE/PI3K-Akt signal pathway.

Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome.

Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS.

Real-time vascular imaging and photodynamic therapy efficacy with micelle-nanocarrier delivery of chlorin e6 to the microenvironment of melanoma.

BACKGROUND: Strategies combining anti-vascular therapy and vascular imaging may facilitate the prediction of early response and outcome in cancer treatment. OBJECTIVE: The aim of this study was to investigate the relationship between the tumor-associated vasculature in melanoma and to develop an approach for melanoma treatment by utilizing the free form and micelle form of the photosensitizer (PS) chlorin e6 in photodynamic therapy (PDT). METHODS: Green fluorescence protein (GFP) expressing B16-F10 melanoma cells were implanted into the mouse ear dermis. Ce6 in free form or in micelle form was administered via the tail vein. An OV100 imaging system was used to record the red fluorescence of Ce6 to obtain real-time vascular images in the GFP tumor. RESULTS: Compared to free Ce6, Ce6 linked to the micelle-nanocarrier depicted a much clearer vascular image and had an effective vascular destruction by PDT. Micelle Ce6 was localized in lysosomes and in the endoplasmic reticulum of cultured endothelial cells, implying an active endocytosis of the nano-carrier. CONCLUSION: Micelle Ce6 can serve as a bifunctional PS for vascular imaging and PDT, which facilitates its delivery in the tumor microenvironment.

Relationship between the degree of displacement and the Baumnann angle in pediatric supracondylar humeral fractures / 中国骨伤

<p><b>OBJECTIVE</b>To analyze the relationship between the degree of displacement and Baumann angle in pediatric supracondylar humeral fractures by using Excel, and to guide treatment for humeral fractures of children.</p><p><b>METHODS</b>From July 2010 to July 2011,56 children with humeral supracondylar fractures were collected (34 boys and 22 girls, 15 patients with radial deviation and 41 patients with ulnar deviation,ranging in age from 3 to 14 years). The data of the patients about fracture displacement and the Baumann angle measured by MB-Ruler were input in Excel and then were analyzed to obtain data fitting curve.</p><p><b>RESULTS</b>There were close results between two methods, and the tangent of the radial deviation was more than tangent of ulnar deviation, which indicated that the influence of ulnar deviation was stronger than that of the radial deviation in pediatric supracondylar humeral fractures,so the correction should be paid attention to in clinic. When the radial deviation coefficient was less than -0.18 and ulnar deviation coefficient was more than 0.50,the Baumann angle would change to the reverse trend, so the angle range of Baumann in clinic should be between 65.70 and 96.77 degree. When the ulnar deviation factor was more than 0.15(including 0.15) and Baumann angle more than 82 degrees(including 82 degree), cubitus varus deformity occurred inevitably,so the practices and surgical reduction should be focused on in clinic.</p><p><b>CONCLUSION</b>According to data curves analysis results,the influence of ulnar deviation is stronger than that of the radial deviation in pediatric supracondylar humeral fractures. When the ulnar deviation factor is more than 0.15 (including 0.15), correction should be focused on in order to prevent cubitus varus deformity.</p>

Influence of serum containing Liuwei Dihuang decoction (see text) on proliferation of osteoblasts under stretch-stress environment / 中国骨伤

<p><b>OBJECTIVE</b>To study influence of serum containing Liuwei Dihuang decoction (see text) on proliferation and differentiation of osteoblast form neonatal SD rats cultured in vitro at different times and different stretch stress.</p><p><b>METHODS</b>After osteoblast cultured for 24 hours in the serum containing Liuwei Dihuang decoction (see text) and serum in control group, the 0.5 Hz frequency, 6% and 12% stretch-stress were added. The MTT1 and the activity of ALP were measured at the 12th and 24th hours, and the data were analyzed.</p><p><b>RESULTS</b>1. In the environment of stretch stress to the frequency of 0.5 Hz, and stretched for 24 hours, the osteoblast was stimulated under elongation rate of 6% and 12%; the proliferation and differentiation of osteoblast was more active under elongation rate of 12% than that of 6%. 2. There were no stimulating effects on osteoblast proliferation and differentiation of serum containing Liuwei Dihuiang decoction (see text) acted on osteoblast cells of SD rats cultured in vitro for a shot time.</p><p><b>CONCLUSION</b>Stretch stress environment can enhance osteoblast proliferation and differentiation cultured in vitro.</p>

Experimental study on the isolated culture of osteocytes and identification of osteoblasts in rats / 中国骨伤

<p><b>OBJECTIVE</b>To establish a more stable method to isolate osteocytes in vitro, and then to find the differences with osteoblast biological characteristics.</p><p><b>METHODS</b>Osteocytes and osteoblasts were isolated from the bone tissue of 3-day-old rats using sequential collagenase digestion. The cells were identified through cell morphology after 24 hours later. Alkaline phosphatase (ALP) kit was used to stain the first generation cells by Kaplow-way, the bone gla protein (BGP) of the cells were stained by immunocytochemitry. Measured ALP and computed its activity.</p><p><b>RESULTS</b>Osteocytes and osteoblasts showed obviously differences in cell morphology. Osteocytes were star-shaped or dendrite-shaped within more dendrites, while osteoblasts were spindle-shaped with short dendrites. Osteocytes were negative for ALP, but osteoblasts were positive; Osteocytes were more positive for BGP, and osteoblasts were less positive. The secretion of ALP in osteocytes was lower than that of osteoblasts.</p><p><b>CONCLUSION</b>Osteocytes can be isolated and cultured in vitro. These characteristics of osteocytes are apparently difference with those of osteoblasts.</p>

Progress on tantalum rod implanting for the treatment of femur head necrosis / 中国骨伤

Incorrect treatment for femur head necrosis can cause collapse of femoral head and tresult in severe harm for the patients (especially for the patient with middle-aged and young). The structure and mechanics characteristics of tantalum rod is similar to bone tissue, it higher strength and can adapt the internal environment of organism, so it has a large potency in treating femur head necrosis. Treatment of early femur head necrosis with tantalum rod implanting had alreadly widey applied at home and abroad, the method has the advantages of simple operation, little risk, less complication and beseems the patient with stage I - II of ARCO. But reasons that the difficult diagnosis of early femur head necrosis, localized effect of tantalum rod, different experience of medical worker,caused the contentions about effect of tantalum rod implanting. With development of science, tantalum rod implanting combined with correlative biotechnology should raise the effect in treating femur head necrosis.

Study on the correlation between short,long term efficacy with cut width in primary angle closure glaucoma iris weeks after cutting holes / 中国基层医药

Objective To investigate the primary angle-closure glaucoma iris weeks after cutting holes cut the width of the near future, long-term effect relationship, selected after close to long-term efficacy of the forecasting methods to improve iridectomy success rate. Methods 90 cases (116 eyes) with primary angle-closure glaucoma were randomly divided into three groups:A group(the width of the iris-week cut-hole cut 1.5mm) ,30 cases 42 eyes;B group(removal of the width of the iris weeks Ceccon 2 mm) ,30 cases 40 eyes;C group(the width of the iris-week cut-lole cut 3 mm) ,30 cases 34 eyes,after over 1 month,they were followed up to observe the intraocular pressure,anterior chamber angle width of the depth, depending on the features, the iris in recent weeks, as well as cutting holes,long-term concurrency disease. Results A:recent surgery success rate of 85.79% ,long-term surgical success rate of 76. 19% ;B group of recent surgery success rate of 87.5% ,long-term surgical success rate of 82.5% ;C group of recent surgery success rate of94.11% ,long-term surgical the success rate of 88.23%, X2 test the difference was significant(P＜ 0. 05) ;3 postoperative IOP decreased in varying degrees compared with the preoperative differences were significant(P＜0.01) ;peripheral angle after deep Random mean :A group of ≥ 1/3CT,compared the difference between before and after surgery were significantly( P ＜ 0.01 ) ;B group and C group ＞ 1/2CT,2 groups were compared before and after surgery the difference was highly significant( P ＜ 0.05 ). Conclusion Iridectomy was the treatment of primary angle-closure glaucoma safe and effective method of cutting holes. The width of the iris weeks to 2～3 mmwas appropriate, beneficial to control the iris weeks before the adhesion and angle-cut hole shallow narrowing.

Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum / 中国中药杂志

<p><b>OBJECTIVE</b>To study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity.</p><p><b>METHOD</b>BCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system.</p><p><b>RESULT</b>D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection.</p><p><b>CONCLUSION</b>The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.</p>