LncRNA SNHG4 regulates miR-152-3p during osteoblastic differentiation of periodontal ligament stem cells / 中国组织工程研究

BACKGROUND:Studies have shown that long non-coding RNA small nucleolar RNA host gene 4(lncRNA SNHG4)is involved in the progress of many inflammatory diseases,but the effect of lncRNA SNHG4 on the osteogenic differentiation of human periodontal ligament stem cells during the treatment of periodontitis is still unclear. OBJECTIVE:To investigate the effect of lncRNA SNHG4 on the osteogenic differentiation of human periodontal ligament stem cells by regulating miR-152-3p. METHODS:Human periodontal ligament stem cells were isolated from periodontal membranes of premolars extracted for orthodontic purposes.After human periodontal ligament stem cells were induced to differentiate into osteoblasts for 0,7,and 14 days,the expression levels of RUNX family transcription factor 2,osteocalcin mRNA,lncRNA SNHG4 and miR-152-3p in human periodontal ligament stem cells were detected by qRT-PCR.The third-generation human periodontal ligament stem cells were divided into the NC group,pcDNA group,pcDNA-SNHG4 group,inhibitor NC group,miR-152-3p inhibitor group,pcDNA-SNHG4+mimic NC group,and pcDNA-SNHG4+miR-152-3p mimic group.The expression of lncRNA SNHG4 and miR-152-3p in human periodontal ligament stem cells was detected by qRT-PCR.The proliferation of human periodontal ligament stem cells was detected by CCK-8 assay.Alkaline phosphatase activity was detected by colorimetry.The formation of mineralized nodules was detected by alizarin red staining.Western blot assay was used to detect the expression of RUNX family transcription factor 2,osteocalcin and alkaline phosphatase proteins.A double luciferase reporter gene experiment was applied to verify the relationship between lncRNA SNHG4 and miR-152-3p. RESULTS AND CONCLUSION:(1)The expression of RUNX family transcription factor 2,osteocalcin mRNA and lncRNA SNHG4 in human periodontal ligament stem cells after 7 and 14 days of osteogenic induction was higher than that after 0 days of osteogenic induction,while the expression of miR-152-3p was lower(P<0.05).(2)Overexpression of lncRNA SNHG4 or inhibition of miR-152-3p was able to enhance the proliferation of human periodontal ligament stem cells,the alkaline phosphatase activity,mineralized nodule formation,the expression of RUNX family transcription factor 2,osteocalcin,and alkaline phosphatase proteins(P<0.05).miR-152-3p mimic attenuated the promoting effect of overexpression of lncRNA SNHG4 on osteogenic differentiation of human periodontal ligament stem cells.LncRNA SNHG4 had a targeting relationship with miR-152-3p.(3)These findings indicate that overexpression of lncRNA SNHG4 may promote the osteogenic differentiation of human periodontal ligament stem cells by inhibiting miR-152-3p.

Impact of BRCA1/2 germline mutation on the incidence of second primary cancer following postoperative radiotherapy in patients with triple-negative breast cancer / 中国癌症杂志

Background and purpose:BRCA1/2 plays an important role in maintaining the genome stability.Whether BRCA1/2 germline mutation could increase the tumor sensitivity to radiotherapy,thereby inducing secondary primary cancer after radiotherapy is unclear.This study aimed to investigate whether postoperative radiotherapy is a risk factor for the development of second primary cancer in triple-negative breast cancer(TNBC)patients with BRCA1/2 germline mutation.Methods:This research was based on a previously reported retrospective cohort,i.e.,the Fudan University Shanghai Cancer Center TNBC cohort.Between January 1,2007 and December 31,2014,a total of 292 female TNBC patients with BRCA1/2 mutation were enrolled.We performed logistic regression analysis in patients without BRCA1/2 germline mutation(n=261)and BRCA1/2 germline mutation patients(n=31),respectively,to assess the risk factors affecting the incidence of second primary cancer.We then performed interactive analysis on the above two analyses to evaluate the interactive effect between BRCA1/2 germline mutation and postoperative radiotherapy.P<0.05 indicates a statistically significant difference.The research was approved by Fudan University Shanghai Cancer Center TNBC Ethics Committee(050432-4-2108),and each patient provided written informed consent.Results:Logistic regression analysis in patients with BRCA1/2 germline mutations showed that postoperative radiotherapy significantly increased the risk of secondary primary disease compared to non-radiotherapy[odds ratio(OR)=2.475,95%confidence interval(CI):1.933-3.167,P<0.001].In patients without BRCA1/2 germline mutation,the effect of radiotherapy on the incidence of second primary tumor was not significant.There was a significant interaction between BRCA1/2 germline mutation and postoperative radiotherapy for the incidence of secondary primary cancer(OR=9.710,95%CI:0.320-295.250,P=0.193).Conclusion:Although statistical analysis results show that patients with BRCA1/2 germline mutations have an increased risk of developing a second primary tumor after postoperative radiotherapy compared to patients who have not received radiotherapy,there is no significant correlation between BRCA1/2 germline mutations and radiotherapy for the development of a second primary tumor.Therefore,patients with BRCA1/2 germline mutations who receive radiotherapy after surgery may not increase the risk of developing a second primary tumor.

Intratumoral and peritumoral radiomics features of apparent diffusion coefficient for predicting prognosis of children with medulloblastoma / 中国医学影像技术

Objective To observe the value of intratumoral and peritumoral radiomics features of apparent diffusion coefficient(ADC)for predicting prognosis of children with medulloblastoma(MB).Methods Data of 74 children with MB were retrospectively analyzed.The children were divided into progression group(n=29)or non-progression group(n=45)according to results of 2-year follow-up,also into training set(n=44)or validation set(n=30)at the ratio of 6∶4.The intratumoral and peritumoral radiomics features were extracted and screened based on ADC images.The intratumoral,peritumoralas well as intratumoral+peritumoral radiomics models were established,and 3 combination models were constructed combining with clinical and conventional imaging features.The predictive efficiency were compared between each 2 combination models.Results In training set,the area under the curve(AUC)of clinical-conventional imaging-peritumoral radiomics model and clinical-conventional imaging-intratumoral+peritumoral radiomics model were both larger than that of peritumoral radiomics models(both P＜0.05).In validation set,AUC of clinical-conventional imaging-intratumoral+peritumoral radiomics model was the largest,but no significant difference of AUC was found among 3 combination models(all P＞0.05).Conclusion The intratumoral and peritumoral ADC radiomics features could be used to predict prognosis of MB children.Combining with clinical and conventional imaging features might improve the efficiency of prediction.

Application of cell-free transcription and translation system in CRISPR technologies and the associated biosensors / 生物工程学报

Cell-free transcription and translation (TXTL) system is a cell extract-based system for rapid in vitro protein expression. The system bypasses routine laboratory processes such as bacterial transformation, clonal screening and cell lysis, which allows more precise and convenient control of reaction substrates, reduces the impact of bacteria on protein production, and provides a high degree of versatility and flexibility. In recent years, TXTL has been widely used as an emerging platform in clusterd regularly interspaced short palindromic repeat (CRISPR) technologies, enabling more rapid and convenient characterization of CRISPR/Cas systems, including screening highly specific gRNAs as well as anti-CRISPR proteins. Furthermore, TXTL-based CRISPR biosensors combined with biological materials and gene circuits are able to detect pathogens through validation of related antibiotics and nucleic acid-based markers, respectively. The reagents can be freeze-dried to improve portability and achieve point-of-care testing with high sensitivity. In addition, combinations of the sensor with programmable circuit elements and other technologies provide a non-biological alternative to whole-cell biosensors, which can improve biosafety and accelerate its application for approval. Here, this review discusses the TXTL-based characterization of CRISPR and their applications in biosensors, to facilitate the development of TXTL-based CRISPR/Cas systems in biosensors.

Mahuang Shengmatang Based on Five Depression Syndromes in Huangdi Neijing / 中国实验方剂学杂志

Mahuang Shengmatang was first recorded in the chapter "Reverting Yin Diseases" in the Treatise on Cold Damage （《伤寒论》）. Whether it is a classic prescription created by ZHANG Zhong-jing is controversial among scholars and physicians due to its distinctiveness in contexts and drug composition. In fact， its proven efficacy in a number of clinical cases cannot be denied， and it is rather biased to judge that Mahuang Shengmatang is a fallacy of later generations. The present study pointed out that Mahuang Shengmatang was a representative in the Treatise on Cold Damage in the treatment of diseases with complicated syndromes. In this formula， although the compatibility of drugs effective in dispersion， astringing， nourishing Yin， assisting Yang， clearing heat， dissipating cold， ascending， floating， sinking， and descending seems complex， it follows certain therapeutic principles. Five depression syndromes in the Huangdi Neijing （《黄帝内经》） highly reflect the Five Elements losing the nature， and embody multiple characteristics of the five elements， such as the movement forms， functions， and disease nature. Furthermore， the corresponding treatment methods were pointed out in the Plain Questions · Major Discussion on the Progress of the Six Climatic Changes of Huangdi′s Internal Classic， including "stagnation of wood should be treated by smoothing， stagnation of fire by dispersing， stagnation of earth by attacking， stagnation of metal by dredging， and stagnation of water by inhibiting"， aiming to restore the physiological conditions of the five elements. The indicated syndromes of Mahuang Shengmatang are complex in superior-inferior， asthenia-sthenia， and cold-heat. The five depression syndromes and their treatment methods recorded in the Huangdi's Internal Classic can reflect the key syndrome pathogenesis and therapeutic principles， which are conducive to analyzing the syndrome differentiation and formulating principles of Mahuang Shengmatang. In the disease progression， impaired Yang Qi in greater Yin and inward invasion of cold pathogens in reverting Yin happen in the initial stage of indicated syndromes of Mahuang Shengmatang， with characteristics of water stagnation， earth stagnation， and wood stagnation. Furthermore， mental stagnation and fire stagnation triggered by Yang Qi accumulation in greater Yang and Yang brightness are the secondary consequences. The compatibility of five types of drugs in Mahuang Shengmatang can act on five depression syndromes in a targeted manner. Based on the five-depression theory in the Huangdi′s Internal Classic and available literature， the present study summarized syndrome pathogenesis and medication characteristics of Mahuang Shengmatang， clarified the correlation between formula and syndrome， and reviewed clinical reports in recent years， which is expected to provide references for the clinical application of Mahuang Shengmatang.

Key performance indexes of two HBsAg ELISA reagents: A retrospectively comparative analysis / 中国输血杂志

【Objective】 To retrospectively analyze the key performance indicators of two hepatitis B surface antigen (HBsAg) ELISA reagents used in blood stations, so as to provide basis for reagent selection from the perspective of laboratory performance. 【Methods】 The test results, reactive rate of initial/repeat test, concordance rate of initial and repeat test, and the NAT-yield implicated in ELISA-reactive samples with one assay from 2016 to 2019 were analyzed to compare the detection performance of two ELISA reagents. 【Results】 The total ELISA reactive rate of HBsAg was 0.39%(1 863/480 741), with 0.31% and 0.29% in two reagents, respectively. The initial reactive rate were 0.44% and 0.39%, concordance rate of initial and repeat test was 70.21% and 74.55%, respectively. 43 NAT-yield samples were implicated in ELISA-reactive samples with one assay. 【Conclusion】 There are differences underlying in the detection performance of the two reagents. In order to avoid blood waste and ensure blood safety, the key performance indexes and test results should be taken into consideration when selecting reagents.

Distribution and haplotype polymorphism of HLA-A、-B、-C、-DRB1、-DQB1 alleles in Anhui Han population / 中国输血杂志

【Objective】 To study the distribution and haplotype polymorphism of HLA-A, -B, -C, -DRB1, -DQB1 alleles in Anhui Han population. 【Methods】 The HLA-A, -B, -C, -DRB1 and -DQB1 genotyping of 3 169 random unrelated stem cell donors was performed by PCR-SBT. The allele frequency, haplotype frequency and linkage imbalance parameters were calculated by counting method, maximum expectation algorithm and PyPop software. 【Results】 A total of 411 HLA alleles were detected in the population, of which 67, 143, 65, 75 and 64 alleles were detected for HLA-A, -B, -C, -DRB1 and -DQB1, respectively. The alleles with frequency >0.1 were HLA-A*11∶01, A*11∶01, A*24∶02, A*02∶01, C*01∶02, C*07∶02, C*06∶02, DRB1*09∶01, DRB1*15∶01, DRB1*07∶01, DQB1* 03∶01, DQB1* 03∶03, and DQB1*02∶01. 1426 HLA-A~HLA-B, 1 772 HLA-B~HLA-DRB1, 798 HLA-B~HLA-C, and 446 HLA-DRB1~HLA-DQB1 haplotypes were detected. The haplotypes showed linkage imbalance, and 19 of them showed strong linkage imbalance (RLD>0.80). 【Conclusion】 The frequency and haplotype distribution of HLA-A, -B, -C, -DRB1 and -DQB1 alleles in Anhui Han population were obtained. The distribution of those alleles and haplotypes have their own characteristics.

Incidence of unintended pregnancy within 2 years after delivery and its influencing factors in China / 中华妇产科杂志

Objective:To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China.Methods:Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women′s socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis.Results:A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95% CI: 4.5%－6.1%) and 13.1% (95% CI: 11.3%－14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions:In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.

CD127 imprints functional heterogeneity to diversify monocyte responses in human inflammatory diseases

Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.

Advance of diagnosis and medical treatment for neonatal necrotizing enterocolitis / 中华实用儿科临床杂志

Necrotizing enterocolitis (NEC) is one of the acquired intestinal inflammatory disease in neonate, with a high mortality rate.The morbidity and mortality rate of NEC remain at high level although recognition for NEC has been improved in last decades.Understanding of this disease has been furthered in latest years.The research advance of NEC is reviewed in present which is focus on the diagnosis and medical treatment to provide new evidence for further study.

Screening and confirmation of TP antibody and analysis of syphilis infection status among 12 295 blood donors in Huainan area / 中国基层医药

Objective:To understand the current situation of syphilis infection among 12 295 blood donors in Huainan area, so as to provide reference for the management of public health.Methods:The Treponema pallidum(TP) antibody of the blood donors was screened by enzyme-linked immunosorbent assay, and the unqualified blood donors for TP antibody were confirmed by Treponema pallidum particle agglutination(TPPA).Results:There were 48 blood donors TPPA positive among 12 295 blood donors in Huainan area, and the TPPA positive rate was 3.90‰(48/12 295). There was no statistically significant difference in the TPPA positive rate of the different gender blood donors[male 3.12‰(22/7 048) vs.female 4.96‰(26/5 247)] in Huainan area( u=1.61, P>0.05). There was statistically significant difference in the TPPA positive rate of the different marriage blood donors[married 5.33‰(42/7 884) vs.unmarried 2.01‰(6/2 989)] in Huainan area( u=2.33, P<0.05). There was statistically significant difference in the TPPA positive rate of the blood donors among different education level in Huainan area(χ 2=29.94, P<0.05). There was no statistically significant difference in the TPPA positive rate of the blood donors among ABO blood groups in Huainan area(χ 2=2.24, P>0.05). Conclusion:There are significant differences in the TPPA positive rates of the blood donors among marital status and education level in Huainan area.

The mediating effect of self-esteem between childhood trauma and aggressive behavior in patients with major depressive disorder / 中华行为医学与脑科学杂志

Objective:To explore the relationship between childhood trauma and aggressive behavior in patients with major depressive disorder(MDD), and the mediating role of self-esteem in childhood trauma and aggression.Methods:A total of 241 MDD patients with childhood trauma were investigated by Chinese version of the Buss & Perry aggression questionnaire(AQ-CV) and self-esteem scale (SES). Data were analyzed by SPSS 23.0 and AMOS 24.0.Pearson correlation analysis was used to assess the correlation of childhood trauma, aggressive behavior and self-esteem.The Bootstrap method was applied to test the mediating effect of self-esteem between childhood trauma and aggressive behavior.Results:The total score of attack questionnaire, self-esteem and childhood trauma were (48.81±18.81), (24.91±5.29)and(53.87±10.43), respectively. Self-esteem of MDD patients was negatively correlated with aggressive behavior and childhood trauma ( r=-0.45, -0.24, P<0.01). Childhood trauma was positively correlated with aggressive behavior ( r=0.42, P<0.01). The direct effect of childhood trauma on aggressive behavior was 0.438(95% CI: 0.305, 0.579). Self-esteem played a partly mediating effect between childhood trauma and aggressive behavior, and the mediating effect value was 0.161 (95% CI: 0.080, 0.256), accounted for 26.9% of the total effect. Conclusion:Self-esteem plays a partly mediating role between childhood trauma and aggressive behavior.Childhood trauma can directly and through the part of mediating role of self-esteem affect aggressive behavior.

TMEM43-S358L mutation enhances NF-κB-TGFβ signal cascade in arrhythmogenic right ventricular dysplasia/cardiomyopathy

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor κB (NF-κB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFβ1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development.

Study on Improvement Effect and Mechanism of Shuangshen Yin on Liver Fibrosis Model Rats / 中国药房

OBJECTIVE： To study improvement effect and mechanism of Shuangshen yin on liver function and the degree of liver fibrosis in liver fibrosis model rats. METHODS： Healthy SD rats were collected and given 40％ CCl4 olive oil solution intraperitoneally for consecutive 7 weeks to induce liver fibrosis model. 47 model rats were randomly divided into model group， positive control group and Shuangshen yin low-dose， medium-dose and high-dose groups， with 9， 9， 9， 10， 10 rats respectively； another 10 healthy SD rats were included in normal group. From the next week after model induction， model group and normal group were given water intragastrically； positive control group [colchicines 0.2 mg/（kg·d）] and Shuangshenyin groups [Shuangshen yin water decoction 3， 6， 12 g/（kg·d）， by crude drug] were given corresponding medicines respectively for consecutive 28 d. The serum levels of liver function indicators （ALT， AST， TBIL， ALB， GLB） were determined by Rye’s analysis method. The serum levels of liver fibrosis indexes （HA， LN， Ⅲ-PC， Ⅳ-C） were determined by ELISA. The pathological changes of liver tissues were observed by HE staining and VG staining. The levels of SOD， MDA and HYP in liver tissues were determined by spectrophotometry. The expression of α-SMA was detected by immunohistochemistry. RESULTS： Compared with normal group， the serum levels of ALT， AST， TBIL， HA， LN， PC-Ⅲ and Ⅳ-C in model group were increased significantly， and the level of ALB was decreased significantly （P＜0.05）. There were some pathological phenomena such as vacuolar degeneration and fibrous tissue proliferation in rat liver. The levels of SOD in liver tissue were decreased significantly， while the levels of MDA and HYP were increased significantly （P＜0.05）. A large number of positive staining granules of α-SMA protein were observed in liver tissue， and the expression level of α-SMA protein was significantly increased （P＜0.05）. Comparison of model group， the serum levels of ALT， AST and liver fibrosis indexes were significantly decreased and ALB level was significantly increased in Shuangshen yin groups， while the TBIL levels in Shuangshen yin medium-dose， high-dose groups were significantly decreased （P＜0.05）； the phenomena of hepatocyte degeneration and fibrosis tissue proliferation were significantly improved； the levels of SOD in liver tissue were significantly increased， and the levels of MDA and HYP were significantly decreased （P＜0.05）； the positive staining of α-SMA protein decreased significantly， and the expression level of α-SMA protein was decreased significantly （P＜0.05）. CONCLUSIONS： Shuangshen yin has protective and anti-fibrotic effects on liver in rats with hepatic fibrosis， the mechanism of which may be associated with enhancing antioxidant capacity， down-regulating the expression of α-SMA， inhibiting the activation of hepatic stellate cells， reducing extracellular matrix synthesis so as to reverse liver fibrosis.

Induction of heme oxygenas-1 attenuates NLRP3 inflammasome activation in lipopolysaccharide-induced mastitis in mice.

Mastitis is one of most prevalent production disease in dairy herds worldwide, and is responsible for enormous economic losses. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme, which is involved in the response to oxidative stress and inflammatory response. The purpose of this study was to detect the protective effect of HO-1 on LPS-induced mastitis in mice. BALB/c mice were pretreated with hemin (HO-1 inducer) and zinc protoporphyrin (ZnPP; HO-1 inhibitor) at 2h before LPS stimulation. The results showed that the mammary gland damage, production of inflammatory cytokines IL-1ß, and MPO activity in mammary gland tissues were significantly reduced after pretreated with hemin compared with the group of LPS stimulation only. However, ZnPP reversed the effects of hemin. Furthermore, we found that the levels of ROS and NLRP3 inflammasome were increased after LPS stimulation. The increases were inhibited by hemin and the inhibition of hemin on ROS production and NLRP3 inflammasome activation were blocked by ZnPP. In addition, the results showed that hemin reduced the expression of thioredoxin-interacting protein (TXNIP) induced by LPS, and ZnPP attenuated these changes. In conclusion, the results suggested that overproduction of HO-1 may inhibit the activation of NLRP3 inflammasome and the expression of TXNIP. Induction of HO-1 may be served as a promising method against mastitis induced by LPS.

Regulation of gene expression via control of transcription elongation during immune responses / 中国免疫学杂志

Transcription is a multi-stage process that coordinates several steps during the transcription cycle including pre-initiation,initiation and elongation.Recent advances by genome-wide study suggest that control of transcription elongation is a critical step for precise regulation of gene expression across species from Drosophila to mammals.Here we review the molecular mechanisms of how transcription elongation of RNA polymeraseⅡ(PolⅡ) is modulated by the major pausing factors-NELF,DSIF and the positive elongation factor P-TEFb,which is the key player in pause release.We also discuss the potential implications of regulation of transcription elongation in pathogenesis of cancer,inflammation and virus infection.

Role of Notch signaling in regulating innate immunity and inflammation in health and disease

The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.

RBP-J is required for M2 macrophage polarization in response to chitin and mediates expression of a subset of M2 genes

Development of alternatively activated (M2) macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP-J as an essential regulator of differentiation and function of alternatively activated macrophages.

Comparison of human and Drosophila atlastin GTPases

Formation of the endoplasmic reticulum (ER) network requires homotypic membrane fusion, which involves a class of atlastin (ATL) GTPases. Purified Drosophila ATL is capable of mediating vesicle fusion in vitro, but such activity has not been reported for any other ATLs. Here, we determined the preliminary crystal structure of the cytosolic segment of Drosophila ATL in a GDP-bound state. The structure reveals a GTPase domain dimer with the subsequent three-helix bundles associating with their own GTPase domains and pointing in opposite directions. This conformation is similar to that of human ATL1, to which GDP and high concentrations of inorganic phosphate, but not GDP only, were included. Drosophila ATL restored ER morphology defects in mammalian cells lacking ATLs, and measurements of nucleotide-dependent dimerization and GTPase activity were comparable for Drosophila ATL and human ATL1. However, purified and reconstituted human ATL1 exhibited no in vitro fusion activity. When the cytosolic segment of human ATL1 was connected to the transmembrane (TM) region and C-terminal tail (CT) of Drosophila ATL, the chimera still exhibited no fusion activity, though its GTPase activity was normal. These results suggest that GDP-bound ATLs may adopt multiple conformations and the in vitro fusion activity of ATL cannot be achieved by a simple collection of functional domains.

Analysis of the clinical risk factors of type 2 diabetes complicated with cerebral infarction / 国际检验医学杂志

Objective To analyze the clinical risk factors of type 2 diabetes complicated with cerebral infarction .Methods 508 patients with type 2 diabetes were selected and divided into two groups :group A (complicated with cerebral infarction ,n=240) and group B (without cerebral infarction ,n=268) .The basic clinical information of two groups were recorded .The coagulation indica‐tors and biochemical indicators (including blood glucose ,blood lipid ,HbA1c ,blood β2 microglobulin ,urineβ2 microglobulin ,urine microalbuminuria ,fasting insulin ,fasting C peptide etc) were detected respectively .Results There were significant differences in age ,age at onset of diabetes ,duration of hypertension and systolic blood pressure between group A and group B (P<0 .05) .The in‐cidence of hypertension and coronary heart disease in group A were higher than group B (P<0 .05) .Comparing with group B ,the levels of HbA1c ,ApoB ,fasting insulin ,fasting C‐peptide ,lipoprotein (a) ,Hcy ,blood β2 microglobulin ,urineβ2 microglobulin ,and urine microalbuminuria of group A were significantly different (P<0 .05) .The ATⅢ level of group A was significantly lower than that of group B (P<0 .05) .Conclusion The risk factors of type 2 diabetes complicated with cerebral infarction include age ,hyper‐tension ,HbA1c ,ApoB ,fasting insulin ,fasting C‐peptide ,lipoprotein (a) ,Hcy ,etc make diabetics be more prone to cerebral infarc‐tion ect .