Microglia are the inherent macrophages and immune surveillance cells in the central nervous system (CNS) and compose the first guard of immune defense in CNS .The activation of microglia is one of the pathological features of many CNS diseases and acts as an important role during the multiple sclerosis (MS) process.MS is a CNS disease characterized by neuroinflammatory infiltration , demyelination and axonal damage.Accumulation of activated microglia at the injury site has been observed in brains of MS patients and experimental animals with complicated mechanisms.Microglia have both detrimental and beneficial roles .For instance, microglia have been shown to recruit and reactivate T cells in the CNS and release many detrimental molecules such as proteases , inflammatory cytokines, and free radicals.Conversely, they have also been observed to aid in axonal regeneration and remyelination as well as assist in the clearance of inhibitory myelin debris .In addition, microglia have been shown to release a variety of neurotrophic factors . Cuprizone [oxalic acid bis (cyclohexylidene hydrazide )] is a well-known copper-chelating agent.Cuprizone ingestion in mice induces a highly reproducible demyelination of distinct brain regions .Discussion on the detrimental and beneficial aspects of microglia in cuprizone animal models will serve to better understand the development of MS and find out new therapeutic targets.This review will further our understanding of the dichotomous roles of microglia in cuprizone -induced demyelination in animal models of multiple sclerosis .

Objective The purpose of this study was to review all published reports on thoracic/ abdominal stent graft and investigate the incidence rates of six main adverse events(MAEs):myocardial infarction,paraplegia,renal failure,respiratory failure,stroke and all-cause mortality.Methods Electronic databases(PubMed、Embase、OVID、ProQuest、Elsevier and The Cochrane Library) were searched from inception through May 2014 to identify studies that assessed the safety of thoracic/abdominal aortic coated stents on MAEs.The incidence rates with 95％ confidence intervals(95％ CIs) were derived using a random effects model,considering the heterogeneity between the included studies.Subgroup and sensitivity analyses were applied to explore heterogeneity.Results A total of 152 studies were included in the analysis with 264 arms.For thoracic stent graft,meta-analysis yielded a combined estimated incidence rates of 12.2％,and the most common MAEs was all-cause mortality (8.1％),followed by respiratory failure (6.5 ％).For abdominal stent graft,meta-analysis yielded a combined estimated incidence rates of 4.6％,and the most common MAEs was all-cause mortality(4.0％),followed by myocardial infarction(2.1％).For thoracic and abdominal stent graft,subgroup analysis stratified by age and proportion of males indicated that middle-aged and females have a higher incidence rates of all-cause mortality.Besides,subgroup analysis stratified by follow-up time indicated that the longer follow-up time,the higher incidence rate of all-cause mortality.Conclusion The current evidence indicates that the incidence of MAEs of thoracic and abdominal stent graft is high,and we should pay more attention to the patients and follow up them as long as possible.

The relationship between tumor metabolism and immunity is complex and diverse. To date, the role of tumor-specific metabolic reprogramming in shaping the specific tumor microenvironment in tumor immunotherapy remains unclear. Lactic acid is the main product of glycolysis, and the aerobic glycolysis of tumor cells causes lactic acid to accumulate in the microenvironment. Recent studies have shown that the accumulation of lactic acid in the tumor microenvironment hinders anti-tumor immunity, especially affects the function, differentiation, and metabolism of immune cells, and participates in tumor immune escape, thus promoting tumor. This article reviews the effects of lactate accumulation in the tumor microenvironment on dendritic cells, T cells, NK cells, tumor-associated macrophages, and myeloid-derived suppressor cells. Targeted intervention of lactate production and efflux by tumor cells is expected to become a new strategy for tumor immunotherapy.

Objective To optimize the prescription of flaxseed lignans sustained release tables by central composite design-response surface methodology.MethodsWith HPMC, EC and starch dosage as factors, and flaxseed lignans in 2, 6 and 12 h of cumulative release as evaluation indexes, central composite design-response surface optimization method was used to conduct prescription optimization experiments, and optimized prescription analysis was carried out.Results The optimal prescription of flaxseed lignans sustained release tables was as following: HPMC dosage was 43%; EC was 26%; starch content was 17%. Optimized index forecast values were very close to the observed values. In vitro release test of three selected optimal formulations indicated that there existed high approximation between the observed and estimated values.Conclusion It shows that the established model is suitable for flaxseed lignans sustained release tables, which can be used in the optimization of the prescription of flaxseed lignans sustained release tables.

Objective To investigate any potential and independent demographic and serologic risk factors contributing to bone destruction in patients with rheumatoid arthritis ( RA) . Methods A total of 445 patients with RA were recruited in this study. Three autoantibodies including rheumatoid factor ( RF) , anti-cyclic citrullinated peptide antibody ( anti-CCP antibody) and anti-citrullinated alpha-enolase peptide 1 antibody ( anti-CEP-1 antibody) were quantified by using specific ELISA kits. The hand radiographs of all subjects were graded by using the modified Sharp/van der Heijde score ( Sharp score) . The potential and in-dependent risk factors were assessed by using univariate linear regression analyses and the stepwise multiple regression analysis, respectively. Results Based upon the univariate regression analyses, 7 covariates were identified as the potential risk factors for bone destruction in patients with RA, which were female (β=0. 100, P=0. 035), longer disease duration (β=0. 498, P=3. 26×10-29), RF (β=0. 096, P=0. 042), younger age at onset (β=-0. 312, P=1. 60 × 10-11 ), anti-CCP antibody positive (β=0. 202, P=1.74×10-5), anti-CEP-1 antibody positive (β=0.148, P=0.017) and positive for either anti-CCP or anti-CEP-1 antibodies (β=0. 157, P=1. 42×10-3). However, smoking (β=-0. 121, P=0. 018) were identi-fied as the potential protective factors. The multiple regression analysis indicated that the longer disease du-ration (P=2. 24×10-15) and anti-CCP antibody positive (P=0. 012) were independent risk factors for bone destruction. Conclusion Female, longer disease duration, younger age at onset, RF, anti-CCP and anti-CEP-1antibodies are potential risk factors for bone damage in patients with RA. Moreover, longer disease du-ration and anti-CCP antibody are two independent risk factors contributing to bone destruction in RA.

Abstract: Objective To establish a rapid detection assay based on fluorescence recombinase polymerase amplification (RPA) targeting Necator americanus eggs, and to evaluate its efficacy, providing technical support for rapid detection of Necator americanus in fecal samples. Methods The fluorescence RPA primers and probe were designed based on the cox1 gene of Necator americanus and then screened the optimal combination to develop the assay. The genomic DNA of Necator americanus eggs was diluted to 7 concentration gradients including 100 pg/µL, 10 pg/µL, 1 pg/µL, 100 fg/µL, 10 fg/µL, 1 fg/µL, 0.1 fg/µL, to determine the detection limit of the assay. The specificity of the assay was demonstrated by detected genomic DNA from Schistosoma japonicum, Ascaris lumbricoides, Clonorchis sinensis and Fasciola hepatica. A total of 44 fecal samples were collected and DNA extraction was performed, and the modified Kato-Katz method, semi-nest PCR method, and fluorescent RPA method were simultaneously used for detection to evaluate the sensitivity and specificity. Results The established fluorescence RPA assay can specifically amplify a fragment of 194 bp of the Necator americanus cox1 gene within 20 min, with a detection limit of 10 fg/µL. There was no cross-reactivity with Schistosoma japonicum, Ascaris lumbricoides, Clonorchis sinensis, Fasciola hepatica after specificity validation. In 44 fecal samples, 27 positive samples were detected by the fluorescence RPA assay, and 26 positive samples were detected by both the Kato-Katz and the semi-nested PCR. The fluorescence curve of sample number 1 was slightly higher than the negative control in the later stage of the reaction, but did not show a similar trend to the positive control, and was therefore judged to be a suspected negative sample. Compared with the Kato-Katz method and the semi-nest PCR method, The sensitivity of the fluorescent RPA method were 100.00% and the specificity were 94.44%, and the consistency of the detection results was good (Kappa=0.953>0.75). Conclusions The assay based on the fluorescence RPA is an efficient, sensitive and specific technique for detecting Necator americanus and it can be applied for surveillance and early warning of hookworm infection.

Abstract: Objective To establish a sensitive and specific nucleic acid detection method for Schistosoma japonicum based on loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) technology. Methods The LAMP primers, gRNA and ssDNA probe that target Schistosoma japonicum SjR2 genes were designed according to the principles of LAMP and CRISPR. The LAMP-CRISPR reaction system was established and optimized. The sensitivity and specificity of the method were evaluated against the ten-fold serial dilutions of plasmid containing SjR2 target sequences, as well as genomic DNA at different stages of Schistosoma japonicum and other parasites, including Fasciola hepatica, Schistosoma mansoni, Taenia saginata, Clonorchis sinensis, Ascaris lumbricoides, Necator americanus, Paragonimus westermani, and Echinococcus granulosus. Additionally, 15 schistosome-infected snail and 30 uninfected samples were tested by LAMP-CRISPR and LAMP methods, respectively, to evaluate the potential of this method for screening for infected snails. Results　The developed LAMP-CRISPR method was able to specifically amplify and detect the SjR2 gene of S. japonicum. The optimal reaction temperature was 37 ℃, and the optimal reaction concentrations were both 40 nmol/L for gRNA and Cas12a protein. No cross-reaction was observed with genomic DNA from other parasites such as F. hepatica. The detection limit of the method was 10 copies/μL when testing 10-fold dilutions of recombinant plasmids as a template. Furthermore, the LAMP-CRISPR method was able to accurately detect genomic DNA from S. japonicum at various stages of development, including eggs, cercariae, schistosomula, juvenile worms, and adult worms. The results of testing 45 snail samples showed no significant difference between the LAMP-CRISPR and LAMP methods for detecting infected snails (χ2=0.05, P>0.05). The sensitivity and specificity of the LAMP-CRISPR method were 100.00% (15/15) and 96.67% (29/30), respectively, compared to the gold standard, while the sensitivity and specificity of the LAMP method were 100.00% (15/15) and 93.33% (28/30), respectively. Conclusions　This established LAMP-CRISPR detection method presented good sensitivity, specificity and reliability, making it a promising tool for rapid detection and risk monitoring of S. japonicum.

Folate involves in one-carbon metabolism pathway,which contributes to nucleotide synthesis,amino acid transformation and methylation.Early embryo development requires a number of cell proliferation and differentiation,in which folate plays a vital role.Studies revealed folate supplement lowers the incidence of congenital heart disease (CHD),and single nucleotide polymorphisms of key enzyme in folate metabolism are closely related to CHD.Folate metabolism disorder may cause hyperhomocysteinemia,which is considered as one of the independent risk factors of CHD.Mechanism in folate metabolism disorder and CHD is unclear,and studies indicate that folate metabolism disorder may lead to CHD by various ways,such as perturbing cardiac neural crest formation and migration,inhibiting DNA synthesis and interfering cell proliferation and apoptosis.Therefore,it is important to explore the role of folate metabolism disorder in CHD,which will be helpful in preventing the disease and reducing the disease burden.

ObjectiveTo analyze the epidemiological characteristics of newly diagnosed occupational welder's pneumoconiosis (OWP) in the shipbuilding industry in Guangzhou City from 2006 to 2022. Methods Data on newly diagnosed OWP cases in the shipbuilding industry in Guangzhou City from 2006 to 2022 was collected and ananlyzed from the Health Hazard Monitoring Information System subsystem of the Chinese Disease Prevention and Control System. ResultA total of 250 cases of new welder's pneumoconiosis were diagnosed in the shipbuilding industry in Guangzhou City from 2006 to 2022. The number of new cases per year showed an initial increase followed by a rapid decline, reaching a peak in 2013 (65 cases). Most of the cases were male, accounted for 99.2%. There were 220 cases reported the OWP stage, with the stage Ⅰ and stage Ⅱ cases accounted for 93.6% and 6.4%, respectively, but no stage Ⅲ cases were reported. The median (M) age and the 25th and 75th percentiles (P₂₅, P₇₅) at diagnosis was 43.0 (39.0, 47.0) years and the dust exposure years M (P₂₅, P₇₅) was 11.2 (8.1, 14.7) years. The M of age at diagnosis of new OWP cases in 2015-2018 and 2019-2022 were higher than those in 2006-2010 and 2011-2014, respectively (all P<0.05). The M of dust exposure duration of new OWP cases from 2006-2010 and 2019-2022 was higher than that in cases from 2015-2018 and 2011-2014, respectively (all P<0.05). Most of the small shadows of the cases were circular small p shadows and distributed in the bilateral middle and lower lung zones, with a density mostly of 1/1, according to the X-ray chest films. Conclusion The hazard of welding fumes in the shipbuilding industry in Guangzhou City has been controlled, but the prevention and control of OWP among welders remains severe.

Objective:To prepare ketoprofen-loaded solid lipid nanoparticles ( SLN) and evaluate the properties. Methods: The formula was optimized by orthogonal experiments with the encapsulation efficiency as the index. The optimal preparation was investiga-ted by the morphology, particle size, zeta potential and drug forms. The release property was characterized by a dialysis method and the release process was fitted. Results: The best formula was as follows: poloxamer 0. 1g, Tween-800. 2g, lecithin 0. 15g, glycerol monostearate 0. 05g and ketoprofen 50mg. The particles were spherical in shape with the encapsulation efficiency of 61. 95%, the par-ticle size was 151. 7 nm and the zeta potential was-30. 2 mV. The result of DSC indicated the drug dispersed in the lipid matrix was a-morphous and molecular state. The in-vitro release curve showed the release was rapid at the early stage and then slowed down with the accumulated amount up to (85. 11 ± 7. 62)% in 12h. The drug was released slowly from SLN with the matrix erosion. The release pro-file fitted well with a Higuchi equation. Conclusion: The solid lipid nanoparticles containing ketoprofen exhibit good quality and the preparation method is simple and feasible, therefore, it is valuable to be further studied.