Comparative study on radiological features between serum aquaporin 4 antibody positive and negative neuromyelitis optica spectrum disorder / 中华放射学杂志

Objective:To investigate the clinical and imaging differences between serum aquaporin 4 (AQP4) antibody positive and negative patients with neuromyelitis optica spectrum disorder (NMOSD).Methods:The clinical data and radiologic findings of 89 NMOSD patients diagnosed at Beijing Tiantan Hospital, Capital Medical University from January 2018 to June 2022 were retrospectively analyzed. There were 17 male cases and 72 female cases, aged 18-74 years. According to the results of serum AQP4 antibody test, the patients were divided into AQP4 antibody positive group and AQP4 antibody negative group, and the differences in clinical data, lesion distribution, lesion characteristics, and brain area volume between the 2 groups were compared using independent sample t-test and χ 2 test, and the correlation between brain area volume and expanded disability status scale (EDSS) scores was further investigated using Spearman correlation analysis. Results:There were 68 cases in the AQP4 antibody positive group and 21 cases in the AQP4 antibody negative group. Patients in both groups were predominantly female, but the percentage of females in the AQP4 antibody-positive group (86.8%, 59/68) was higher than that in the AQP4 antibody-negative group (61.9%, 13/21), with a statistically significant difference (χ 2=4.91, P=0.027). The incidence of optic neuritis in AQP4 antibody negative group (66.7%, 14/21) was higher than that in antibody positive group (41.2%, 28/68), with a statistically significant difference (χ 2=4.18, P=0.041). In the distribution of intracranial lesions on MRI, the probability of lesions involving the brain stem in AQP4 antibody negative group (47.6%, 10/21) was higher than that in AQP4 antibody positive group (23.5%, 16/68), the difference had statistically significance (χ 2=4.50, P=0.034). The volumes of whole brain white matter, right amygdala, right accumbens-area and right ventral diencephalon in AQP4 antibody positive group were lower than those in AQP4 antibody negative group ( P<0.05), and the volumes of the right accumbens-area were negatively correlated with the EDSS scores in AQP4 antibody positive group ( r=-0.628, P=0.009). Conclusion:There are differences in clinical and imaging manifestations between AQP4 antibody positive and AQP4 antibody negative patients, which provides more basis for clinical in-depth understanding of NMOSD.

The mechanism of iNKT2 cell improving lipid deposition in the liver of nonalcoholic fatty liver mice / 中华内分泌代谢杂志

Objective:To investigate the mechanism of invariant natural killer T (iNKT)2 cell improving hepatic fat deposition in nonalcoholic fatty liver (NAFL).Methods:NAFL model was established by feeding C57BL/6J mice with high fat diet. The levels of serum total cholesterol, triglyceride, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the peripheral blood of mice were analyzed using automatic biochemical analyzer. The pathological changes of liver were observed with HE staining. The cell frequencies of iNKT, iNKT1, and iNKT2 in liver were detected by flow cytometry. Western blotting was used to detect the expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator activated receptor (PPAR)-α, and nuclear factor-κB (NF-κB) in liver tissues.Results:Compared with control group, the body weight of NAFL mice increased, the levels of total cholesterol, HDL-C, LDL-C, ALT, and liver fat deposition increased, the protein expression of SREBP-1c and PPAR-α in liver increased as well as the the protein phosphorylation level of NF-κB. After intraperitoneal injection of α-galactosylceramide (α-GalCer), the levels of total cholesterol, HDL-C, and LDL-C, liver fat deposition decreased, liver SREBP-1c was down-regulated, PPAR-α expression was up-regulated, and the proportion of liver iNKT2 subgroup increased in NAFL mice.Conclusion:iNKT2 cells improve NAFL liver fat deposition, which is related to the down-regulation of SREBP-1c and up-regulation of PPAR-α.

Machine learning models based on radiomics in diagnosis of pituitary prolactin macroadenoma / 中华放射学杂志

Objective:To explore the effectiveness and feasibility of the machine learning models based on radiomics in the diagnosis of pituitary prolactin macroadenoma.Methods:Totally 122 histologically proven pituitary macroadenoma patients, including 70 cases of pituitary prolactin macroadenoma (PPM) and 52 cases of non-pituitary prolactin macroadenoma (NPPM), were retrospectively recruited. The differences of age, sex, serum prolactin value, bleeding, cystic degeneration and Knosp classification were compared between PPM and NPPM. The pre-processing, delineation of the region of interest and feature extraction of the preoperative axial contrast-enhanced T 1WI image were performed in the 3Dslicer software. The optimal feature set were selected by least absolute shrinkage and selection operator. All patients were randomly divided into the training group ( n=85) and the test group ( n=37) at a ratio of 7∶3. The models were established in the training group by logistic regression and support vector machine (SVM), and then verified by the test group. ROC curves were drawn respectively, and specificity, sensitivity, accuracy and area under the ROC curve (AUC) were calculated. Results:The age [(38±12) years vs . (43±11) years], gender ratio (male/female 50 cases/20 cases vs . 14 cases/38 cases) and prolactin value [366.00 (117.75, 1 156.25)μg/L vs . 47.25 (32.68, 62.40) μg/L] of patients with PPM and NPPM were statistically different ( P<0.05). The AUC values of logistic regression and SVM in the training group were 0.936 and 0.946, and the AUC values of the test group were 0.768 and 0.774, respectively. The diagnostic accuracy of logistic regression and SVM in the training group were 88.2% and 91.8%, and the accuracy of the test group were 73.0% and 77.8%. Conclusion:The machine learning models based on the radiomics can predict the pituitary prolactin macroadenoma well with a high accuracy.

Changes in invariant nature kiler T (iNKT) cell percentages and subsets in immune organs of mice at different stages of obesity / 中华微生物学和免疫学杂志

Objective:To observe the changes in percentages and subsets of invariant nature kiler T (iNKT) cells in adipose and related tissues at different stages of obesity, and analyze the role of iNKT cells during chronic inflammation in adipose tissues in a mouse model of obesity established with high-fat diet.Methods:Changes in mouse body weight, mental state, glucose tolerance and insulin tolerance were recorded. Hematoxylin and eosin (HE) staining was used to observe pathological changes in adipose tissues. Flow cytometry was performed to detect the percentages and subsets of iNKT cells as well as the percentages and subtypes of macrophages. The levels of cytokines in serum samples and the culture supernatants of lymphocytes in adipose tissues were detected with CBA. The expression of related proteins in adipose tissues was detected by Western blot.Results:(1) The volume of adipose cells increased significantly after four weeks of high-fat feeding, but the infiltration of inflammatory cells was not obvious. Significantly increased infiltration of inflammatory cells was observed after 12 weeks of high-fat feeding. (2) High-fat feeding could reduce the percentage of iNKT cells, increase the proportion of iNKT1 subgroup and decrease the proportion of iNKT10 subgroup in adipose tissues. The proportion of iNKT1 subgroup in thymus increased, but that of iNKT2 subgroup decreased. The percentage of macrophages and the proportion of M1 subgroup in adipose tissues increased, while the proportion of M2 subgroup decreased, which were more obvious after 12 weeks of high-fat feeding. (3) High-fat feeding resulted in decreased expression of E4BP4 and arginase-1 (Arg-1) in adipose tissues and increased expression of inducible nitric oxide synthase (iNOS). (4) High-fat feeding significantly increased the pro-inflammatory cytokines and decreased the anti-inflammatory cytokines in mouse serum and culture supernatants of lymphocytes in adipose tissues with more significant changes observed after 12 weeks of high-fat feeding.Conclusions:Increased iNKT1 and decreased iNKT10 in obese adipose tissues might be closely related to the increased M1 polarization and the imbalance of iNKT subsets might be involved in the progression of chronic inflammation in obese adipose tissues.

Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway / 中国天然药物

Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin (HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12 (HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1 (Arg-1), interleukin-10 (IL-10), transforming growth factor β (TGF-β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase (iNOS) was down-regulated in LPS- and IFN-γ-treated (M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490 (inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.

Transforming growth factor-β and renal fibrosis / 生理学报

Transforming growth factor-β (TGF-β) is a driving force of renal fibrosis, which may lead to chronic kidney diseases and even end stage renal diseases. By activating canonical and non-canonical signaling pathways, TGF-β promotes the synthesis of extracellular matrix while preventing their degradation. In the injured kidney, TGF-β induces apoptosis, proliferation and fibrotic response of renal cells including epithelial cells, endothelial cells, podocytes, fibroblasts, pericytes and macrophages, and it also promotes transdifferentiation, activation and proliferation of myofibroblasts. Additionally, TGF-β exerts profibrotic effects by interplaying with other signaling pathways like BMP-7, Wnt/β-catenin and MAP kinase. Smad3 is the central pathological gene in renal fibrosis, and epigenetic regulation of TGF-β/Smad3 is a hot topic in kidney field. Although direct targeting TGF-β may cause side effects including tumorigenesis and immune diseases, the therapeutic strategies targeting the balance of downstream Smad3 and Smad7 may prevent or delay the progression of fibrotic kidney disease.

Risk Management to Shanghai Medical Device Registrants / 中国医疗器械杂志

In Nov.2017, Shanghai CFDA began to pilot medical device registrant project in China. This project is a bold attempt to medical device supervision. And it's quite helpful for promoting innovation and development of medical devices in Shanghai. However, the "R&D-Production-separate" characteristic enhances risks in medical device life-cycle. It also brings more challenges to registrant on medical device risk management. In order to protect interested parties fully and effectively, we will discuss why registrants need to manage risk and what they should pay attention to in this article.

Application of online tests through two-dimensional code in the course of Fundamental Nursing / 中国实用护理杂志

Objective To explore the application effects of online tests through two-dimensional code in the course of Fundamental Nursing. Methods A total of 79 nursing students in 2016 were included in the study. Compared with traditional method in the first term, online tests through two-dimensional code were implemented in the second term. The students′ appraisal on online tests through two-dimensional code was investigated with a self-designed questionnaire. Results The students showed a positive attitude to online tests through two-dimensional code. 97.3%(71/73) of the students thought online tests through two-dimensional code was easy to implement, and 93.2%(68/73) of them agreed that online tests help them to know how they learned and improved the efficiency and quality of class. Conclusions Online tests through two-dimensional code, which are novel, energy-saving and environmental friendly,can improve students′learning interest and enhance learning effect.Therefore,it is worthy to be applied and recommended.

Alcohol promotes renal fibrosis by activating Nox-mediated DNA methylation of Smad7 / 中国药理学与毒理学杂志

OBJECTIVE Alcohol is mainly metabolized through liver and excreted by kidney in the body. Kidney damage has been considered as the secondary to liver injury and kidney dysfunction is common in hospitalized patients with severe alcoholic hepatitis. Both acute and chronic alcoholism accumulation can compromise kidney function, although alcoholic kidney disease has drawn much more attention recently,the methodology for establishing the in vivo and in vitro alcoholic renal fibrosis models are still lacking,and the underlying mechanisms are to be determined. METHODS and RESULTS Mice were feed with a liquid diet containing alcohol for 4 weeks, 8 weeks and 12 weeks respectively, results of Masson′s Trichrome staining showed that kidney fibrosis peaked in 8-week model group, which consistent with the results of albumin assay,Western blot,immunostaining and real-time PCR of collagen I and α-SMA.In vitro study also confirmed that ethanol upregulated the level of fibrotic index-es,including collagen I and α-SMA,in tubular epithelial cells(HK2 cells).Additionally,both in vivo and in vitro studies showed that Smad7 was decreased and Smad3 was highly activated. Then we further detected the underlying mechanisms by which alcohol induced the imbalance of Smad7 and Smad3. Results of Genome-wide methylation sequencing found DNA methylation of Smad7 in the alcoholic fibrosis kidney,which may be mainly mediated by DNA methyltransferase 1(DNMT1),because knock-down of DNMT1,but not DNMT2 and 3,largely restored Smad7 level in ethanol-treated HK2 cells.Con-sequently, we found that NADPH Oxidases (nox)-mediated oxidative stress is the major force upregu-lating DNMT1,since knockdown of Nox2 and 4 could both decrease DNMT1 while rebalancing Smad7/Smad3 axis, and thereby relieved ethanol-induced fibrotic response in HK2 cells. More importantly, intraperitoneal injection of apocynin,an inhibitor of NADPH oxidoreductase,attenuated renal fibrosis in alcoholic kidney fibrosis mouse model. CONCLUSION By establishing the novel in vivo and in vitro models,we found that through activating oxidative stress-induced DNA methylation of Smad7,alcohol induces renal fibrosis by breaking the balance between Smad7 and Smad3.Elimination of Nox-mediated oxidative stress may be a potential therapy for treatment of long-term alcohol abuse-induced kidney fibrosis.

Invariant nature killer T ( iNKT) cell percentages and subsets in non-obese diabetic ( NOD)/LtJ mice with different stages of type 1 diabetes / 中华微生物学和免疫学杂志

Objective To detect and analyze the percentages of CD4+T, CD8+T and invariant na-ture killer T ( iNKT) cells as well as iNKT subsets in different tissues and organs of non-obese diabetic (NOD)/LtJ mice before the onset and in the early and late stages of type 1 diabetes (T1D) for better under-standing the immune function in different disease stages. Methods Female NOD/LtJ mice were selected as experimental subjects. Their fasting blood glucose levels were measured by blood glucose meter. Glycosuria and blood glucose level ≥11. 1 mmol/L in two consecutive detections were used as the diagnostic criteria of T1D. These mice were divided into three groups as follows: non-onset, early stage and late stage groups. Changes in food and water intake, glucose level in the urine, body weight, mental state, fur color and urine volume were recorded. Percentages of CD4+T, CD8+T and iNKT cells and ratios of subsets in peripheral blood, thymus, spleen, liver and inguinal lymph nodes were detected by flow cytometry (FACS). Results (1) Compared with the non-onset and the early stage groups, mice in the late stage group were apathetic and had rough hair. Moreover, significantly increased water and food intake and urine output (P<0. 05) and de-creased body weight, thymus index, spleen index and the absolute lymphocyte counts of spleen, liver and thymus (P<0. 05) were observed in the late stage group. (2) Compared with the non-onset group, the early stage group showed significantly increased percentages of CD4+T cells in spleen, liver, thymus and inguinal lymph nodes (P<0. 05). Compared with the early stage group, the late stage group showed decreased per-centages of CD4+T cells in liver, thymus, inguinal lymph nodes and peripheral blood (P<0. 05). Compared with the non-onset group, the percentages of CD8+T cells in the early stage group were significantly increased in spleen and thymus, but reduced in inguinal lymph nodes (P<0. 05). Compared with the early stage group, the percentages of CD8+T cells in late stage group were significantly reduced in liver and thymus, but increased in inguinal lymph nodes (P<0. 05). (3) The percentages of iNKT cells in liver and inguinal lymph nodes of mice in the early stage group were significantly higher than those of the non-onset group (P<0. 05). The percentages of iNKT cells in peripheral blood and liver of mice in the late stage group were sig-nificantly lower than those of the early stage group (P<0. 05). No significant difference in the percentages of iNKT cells in spleen and thymus was found among the three groups (P>0. 05). (4) Compared with the non-onset group, the percentages of iNKT1 subset in thymus in the early and late stage groups were significantly increased, while the percentages of iNKT2 subset were significantly decreased (P<0. 05). No significant difference in the percentages of iNKT1 and iNKT2 subsets in spleen, liver and inguinal lymph nodes was found among the three groups (P>0. 05). (5) The percentages of iNKT2 subset in spleen, liver and ingui-nal lymph nodes were significantly lower than those of the iNKT1 subset in the three groups (P<0. 05). The percentage of iNKT2 subset in thymus was significantly higher than that of iNKT1 subset in the non-onset group (P<0. 05). (6) Compared with the non-onset and the late stage groups, the early stage group showed significantly increased levels of IFN-γ, IL-4 and IL-17A and up-regulated ratio of IFN-γ/IL-4 (P<0. 05). Compared with the non-onset and the early stage groups, the late stage group showed significantly increased IL-6 level (P<0. 05). Compared with the non-onset group, IL-10 level in the other two groups was in-creased, especially in the late stage group (P<0. 05). No significant difference in IL-2 level was found among the three groups (P>0. 05). Conclusion Increased percentages of iNKT cells and iNKT1 subset in NOD/LtJ mice with early stage of T1D might be involved in the development of T1D.

Application of Intravoxel Incoherent Motion Model-based Diffusion Weighted Imaging in the Diagnosis and Therapy of Breast Cancer / 中国医学科学院学报

Intravoxel incoherent motion model-based diffusion weighted imaging can distinguish the microcirculation reperfusion and true diffusion of water molecules,which can quantitatively or semi-quantitatively reflect the functional state and microstructure features of tissues.Thus,this technique has increasingly been used in breast tumor,especially in the differential diagnosis,pathological classification,and curative effect monitoring of breast cancer.

Effects of immunostimulator CH2 b on mixed peptides derived from glucose-6-phosphate isomerase induces arthritis / 中国免疫学杂志

Objective:To explore the effect of the synthetic immunomodulator CH 2b with a thiazolidin-4-one ring on the pathogenesis of rheumatoid arthritis (RA) mice induced by glucose-6-phosphate isomerase(GPI) mixed peptides.Methods:hGPI325-339 ,hGPI469-483 peptide fragments were mixed with complete freund′s adjuvant fully ,DBA/1 mice were givien subcutaneous injection of the emulsifiers,pertussis toxin to strengthen immunity.And then RA mice were intervened with α-GalCer and CH2b,the changes of body weight ,ankle joint symptoms scores were observed .The joint tissues stained with hematoxylin and eosin ( HE) was used to evaluate the inflammatory cells.Fluorescence-activated cell sorting ( FACS) was used to detect the frequency changes of iNKT cells .Cytometric bead array(CBA) was used to analyze the levels of serum cytokines TNF-α,IL-6,IL-4,IFN-γ.Results: Compared with the model group,α-GalCer,CH2b could reduce the inflammation of the model mice ,significantly improve the body weight growth and the joint swelling(P0.05).Conclusion:Immunomodulator CH2b by activating iNKT cells affect the secretion of inflammatory cytokines ,and it relieved the GPI induced arthritis .

Detection of chloroprene in human blood by headspace gas chromatography / 中国职业医学

OBJECTIVE: To establish a detection method for chloroprene in human blood by headspace gas chromatography.METHODS: The blood sample was placed directly in the headspace bottle,after the head space automatic sampling,the target object was detected by gas chromatography with electron capture detector,quantified by external standard method.RESULTS: The good linearity range of chloroprene was 0. 00-160. 00 μg / L,and the correlation coefficient was 0. 999 4. The detection limit was 0. 10 μg / L and the minimum detectable concentration in blood samples was 0. 10 μg / L. The with-run relative standard deviation( RSD) was 1. 38%-1. 91%,and the between-run RSD was 2. 11%-3. 08%. The average recovery rate was 89. 00%-93. 88%. CONCLUSION: The method has the features of high sensitivity,wide linear range and simple sample processing,which was suitable for efficient detection for large quantity of samples.

Microstructural white matter lesion in Alzheimer's disease：a diffusion tensor imaging study using vox- el-based analysis / 中国神经精神疾病杂志

Objective To study the microscopic changes of white matter and the relationship between white matter changes and cognitive impairment in Alzheimer's disease (AD) using voxel-based analysis of DTI. Methods Thirty-sev?en patients with probable AD,and 32 normal controls(NC) were all examined by MMSE scores, and underwent a diffusion tensor imaging. The value of FA changes and the correlations between FA and MMSE scores were investigated. Results FA reduction was detected in the right frontal, temporal and parietal lobes as well as the thalamus, the bilateral cingu?lum, corpus callosum, precuneus, inferior parietal lobule, inferior patieto gyrus, supramaginal gyrus and hippocampus in AD. FA values in the right cingulum, left corpus callosum, left inferior temporal gyrus and the bilateral inferior parietal lobule, inferior patieto gyrus and precuneus were significantly decreased in AD than in the health control groups (P<0.05, FWE corrected). There was a positive correlation between the values of FA and MMSE scores(P<0.001,uncorrect?ed). Conclusion AD patients have significant reduction of FA values in the specific regions. There is a positive correla?tion between white matter changes and impairments of cognitive function.

Effcets on immunoregulation of iNKT cells in RA by novel synthetic immunos-timulator CH1 b / 中国免疫学杂志

Objective:To investigate effects of a novel synthetic immunostimulator CH1b containing thiazolidin-4-one on the immunoregulation funotion of iNKT ( invariant nature killer T ) cells in active RA patients in vitro.Methods: Peripheral blood mononuclear cells( PBMCs) isolated from active RA patients were cultured with stimulation of α-Galcer and IL-2 in vitro and iNKT cells were then separated by using magnetic activated cell sorting( MACS) method with iNKT isolation kit.The cells were divided into three groups:control group (IL-2),α-Galcer group (IL-2+α-Galcer),CH1b group(IL-2 +CH1b).The effects of CH1b on the proliferation of iNKT cells in active RA patients were analyzed by using MTT assay.MILLIPLEX MAP Human Cytokine/Chemokine kit was used to evaluate the secretion of IFN-γand IL-4 in iNKT cells culture media.The expressions of IFN-γmRNA and IL-4 mRNA in iNKT cells were analyzed by RT-PCR.Results: Compared with control and α-Galcer group,the proliferation of iNKT cells of CH1b group were significantly higher( P<0.05).Compared with control,the ratio of IFN-γ/IL-4 in iNKT cells culture media in active RA patients of CH1b group were significantly lower (P<0.05).Compared with control,expressions of IFN-γmRNA and IL-4 mRNA were higher inα-Galcer group;compared with control,expressions of IL-4 mRNA were higher in CH1b group,while there were no obvious difference on expressions of IFN-γmRNA.Conclusion:CH1b was found to significantly stimulate the actived iNKT cells in active RA patients proliferation,promote the secretion of IL-4,and increase the ratio of IFN-γ/IL-4,promote the expression of IL-4 mRNA in iNKT cells in active patients.

Immunization with mixed peptides derived from glucose-6-phosphate isomerase induces rheumatoid arthritis in DBA/1 mice / 中国病理生理杂志

[ ABSTRACT] AIM:To establish an animal model of rheumatoid arthritis ( RA) in DBA/1 mice induced by im-munodominant mixed peptides derived from glucose-6-phosphate isomerase (GPI).METHODS: The DBA/1 mice were immunized with emulsified mixed peptide fragments of hGPI 325-339+hGPI469-483 or single peptide hGPI325-339 in com-plete Freund′s adjuvant by subcutaneous injection to induce the model of RA .Body weight , ankle joint symptom scores , the pathological change of the ankle joint , the levels of CD4 +T cells in the spleen and peripheral blood , the proportion of iNKT cells in the peripheral blood , and the levels of TNF-αand IL-6 in serum were detected to evaluate and analyze the model.RESULTS:The hind paw of the model mice appeared red swelling on the 8th day, and then aggravated gradually to the limbs.The red swelling reached peak on the 14th day, and then relieved gradually .Inflammation response dominated by lymphocytes and monocytes was observed in the ankle joint .The inflammatory effect of mixed peptides was more obvious than that of the single one (P<0.05).Compared with control group and the mice treated with single peptide , the weight gain was slow, the amount of CD4 +T cells in the peripheral blood and spleen were increased , the proportion of peripheral iNKT cells in the inflammatory peak was decreased (P<0.05), and the serum level of TNF-αwas increased significantly ( P<0.05) in the mice treated with mixed peptide fragments .CONCLUSION: The immunological characteristics of RA model induced by mixed GPI peptides in DBA/1 mice is closer to that in RA patients , especially in the immunopathology of iNKT cells.Therefore, this model can be used as a new tool for studying the mechanism and immunological intervention of RA.

Design and synthesis of photoaffinity biotin labelled 2'-O-propargyl-guanosine / 药学学报

Photoaffinity labeling is widely applied to demonstrate targets of small molecule ligands. In this paper, biotin photoaffinity labeled molecule with propargyl group 1 has been designed and synthesized, followed it's labeling of N2-acetyl-2'-O-propargyl guanosine 9 by "click chemistry". This technology presents delight development potential in labeling of second messenger cyclic nucleotide, antisense oligonucleotide or siRNA.

Study of the correlation between the percentage of iNKT cells and the ratio of IFN-γ/IL-4 in patients with rheumatoid arthritis / 中华微生物学和免疫学杂志

Objective To investigate the alterations of invariant nature killer T( iNKT) cells in peripheral blood samples from patients with rheumatoid arthritis ( RA) and to clarify the correlation between the percentage of iNKT cells and the ratio of IFN-γ/IL-4 in order to further understand the significance of iNKT cells in the development of RA.Methods Peripheral blood mononuclear cells ( PBMCs) were isola-ted from 70 patients with RA and 40 healthy subjects.Among them, thirty patients in the stage of inactive RA were involved in a follow-up study.Fluorescence activated cell sorting ( FACS) was used to detect the percentage of iNKT cells.PBMCs were cultured in vitro for analysis of cytokine production.The dynamic changes of iNKT cells in percentages were analyzed by FACS.MILLIPLEX MAP Human Cytokine/Chemo-kine kit was used to measure the secretion of IFN-γand IL-4 in serum samples and culture media of PBMCs. The expression of IFN-γand IL-4 in iNKT cells at mRNA level were analyzed by RT-PCR.Results Com-pared with the healthy subjects, the patients with active RA showed the delayed proliferation of iNKT cells and the decreased percentages and proliferation rates of iNKT cells (P0.05).The ratios of IFN-γ/IL-4 in serum samples and culture media of PBMCs were increased in patients with active RA as compared with those in patients with inactive RA and healthy subjects (P0.05).Compared with healthy subjects and patients with inactive RA, patients with active RA showed increased transcriptional level of IFN-γand decreased transcriptional level of IL-4.No significant differences with the expression of IFN-γand IL-4 in iNKT cells at mRNA level were observed between healthy subjects and patients with inactive RA.The per-centage of iNKT cells was negatively related to the IFN-γ/IL-4 ratio in patients with RA (P<0.05).Con-clusion Decreased percentage and impaired function of iNKT cells were detected in patients with RA. iNKT cells were closely related to the development and disease activity of RA.

Effects of a novel synthetic immunostimulator CH2b on iNKT cells isolated from patients with active rheumatoid arthritis / 中华微生物学和免疫学杂志

Objective To investigate the effects of a novel synthetic immunostimulator CH2b containing thiazolidin-4-one on the function of invariant nature killer T (iNKT) cells isolated from patients with active rheumatoid arthritis (RA).Methods Peripheral blood mononuclear cells (PBMCs) isolated from patients with active RA were in vitro cultured with α-Galcer and IL-2.The iNKT cells were separated by using magnetic activated cell sorting (MACS) method.The effects of CH2b on the proliferation of iNKT cells were analyzed by using MTT assay.MILLIPLEX MAP Human Cytokine/Chemokine kit was used to measure the levels of IFN-γ and IL-4 in the supernatants of iNKT cell culture.The expressions of IFN-γand IL-4 at mRNA level in iNKT cells were analyzed by RT-PCR.Western blot assay was used to detect the levels of T-bet and GATA-3 in iNKT cells.Results CH2b significantly enhanced the proliferation of IL-2 activated iNKT cells isolated from the patients with active RA.CH2b promoted the secretion of IL-4,resulting in a decrease in the ratio of IFN-γ/IL-4.Moreover,CH2b promoted the expressions of GATA-3 and IL-4 at mRNA level in iNKT cells.Conclusion The novel immunostimulator,CH2b,might enhance the immunoregulatory effects of iNKT cells by promoting the GATA-3 pathway-mediated secretion of Th2-1ike cytokines and inducing the differentiation of Th0 to Th2 cells.

Clinical Characteristics, Radiological Features and Gene Mutation in 10 Chinese Families with Spinocerebellar Ataxias / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs.</p><p><b>METHODS</b>In this study, we investigated 10 SCAs Chinese families with SCA1, SCA3/Machado-Joseph disease (MJD), SCA7, SCA8. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but failed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were performed.</p><p><b>RESULTS</b>We found that SCA3/MJD was the most common subtype in Han population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively correlated with the number of cytosine-adenine-guanine (CAG) repeats; the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset.</p><p><b>CONCLUSIONS</b>Collectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.</p>