Aim To investigate the effect of histamine H, receptor (HjR) on the immune responses in astrocytes induced by lipopolysaccharide (LPS) and the regulatory mechanism of its signaling pathway. Methods LPS was used to establish an in vitro astrocyte inflammation model. Rat primary astrocytes were divided into the control group, LPS group, LPS + Hj R agonist group (2-pyridylethlamine, Pyri), and HjR agonist group. Astrocytes were treated with Pyri 100 p,mol • L~ for 1 h, then stimulated with LPS at 100 p,g • L~ for 24 h. Cell viability was measured using the CCK-8 assay. The expression of GFAP and HjR was detected by immunofluorescence. Glial morphological changes were observed under a microscope. The levels of proinflammatory mediators (TNF-a and IL-6) were detected by ELISA. The protein expressions of p-Akt, Akt, p-NF-KB p65, and NF-KB p65 were detected by Western blot. Results Compared with the control group, more activated astrocytes with fewer cell processes and branches were observed in the LPS group. Besides, LPS enhanced the GFAP expression level, reduced the H,R expression level and stimulated the production of TNF-a and IL-6 from astrocytes. Pre treatment with Pyri for 1 h ameliorated the glial morphological changes stimulated by LPS, inhibited LPS-induced upregulation of GFAP level and the inflammatory factors secretion. In addition, LPS stimulated astrocytes showed a higher phosphorylation of Akt and NF-KB p65, which was also ameliorated by Pyri. Conclusions H, R agonist can inhibit LPS-induced astrocyte activation and inflammatory factor secretion, and the Akt/NF-KB signaling pathway may be an important pathway for the involvement of H,R in immune regulation.

Objective To investigate the imaging features of intestinal schwannoma(IS)in order to improve the diagnostic ability of the disease.Methods The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed,including the location,size,morphology,nature,growth pattern,CT density,MRI signal,PET/CT metabolism and other characteristics of the tumors.Results Of the 14 IS cases,the lesions of 3 cases were located in the duodenum,2 cases in the cecum,8 cases in the colon and 1 case in the rectum.The lesions were all round or oval,with an average maximum diameter of(2.4±1.1)cm.The lesions were solid in 13 cases,extraluminal growth in 10 cases,cystic degeneration in 1 case and myxoid degeneration in 1 case.Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases,and the short diameter of lymph nodes was greater than 5 mm in 6 cases.All 14 cases of IS showed low attenuation on plain CT scan,and progressive enhancement after contrast injection,including 1 case of mild enhancement,2 cases of moderate enhancement,and 11 cases of obvious enhancement.Two cases of IS showed low signal intensity on T1WI,slightly high signal intensity on T2WI,significantly high signal intensity on DWI,and obvious progressive enhancement after contrast injection on MRI.Two cases of IS showed high metabolism on 18F-FDG-PET/CT,and the SUVmax was 9.4 and 8.8,respectively.Conclusion The imaging findings of IS were characteristic to a certain extent.They mainly manifested as solid nodules or masses derived from the intestinal submucosa,with uniform attenuation or signal intensity,obvious progressive enhancement after contrast injection,obvious hypermetabolism on 18F-FDG-PET/CT,and slightly larger homogeneous lymph nodes were common around the lesions.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases.MethodsBased on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (Dmd^Mu/+) mice were obtained after genotype identification. Male hemizygous Dmd^Mu/+(Dmd^Mu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting.An acute inflammation model was established in Dmd^Mu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry.Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (Dmd^Mu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of Dmd^Mu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P<0.05). Compared with wild-type mice of the same background, Dmd^Mu/Y mice at 3 and 9 months of age showed significant weight loss (P<0.01) and decreased muscle tension (P<0.05). 9-month-old Dmd^Mu/Y mice exhibited significant pathological changes in skeletal muscle and myocardium, including widening of intermuscular space. Under normal condition, compared with wild-type mice, the proportion of neutrophils and monocytes in the peripheral blood of 3-month-old Dmd^Mu/Y mice was significantly lower than that of wild-type mice (P<0.01). After lipopolysaccharide stimulation, the proportion of neutrophils in peripheral blood of 3-month-old Dmd^Mu/Y mice remained significantly lower compared to that of wild-type mice (P<0.01). The proportion of neutrophils in peripheral blood of 9-month-old Dmd^Mu/Y mice significantly decreased after lipopolysaccharide induction (P<0.01), with a trend of change observed in monocytes between groups.Conclusion The successful construction of the Dmd gene mutant mouse model has confirmed the vital function of Dmd gene in maintaining normal muscle tissue morphology and muscle tone. It preliminarily indicated that Dmd gene deletion could significantly reduce the proportion of neutrophils in peripheral blood, offering a new perspective for the study of immune system alterations in Duchenne muscular dystrophy patients.

ObjectiveTo observe the effectiveness and safety of the Chinese herbal medicine Mingshi Granules （明视方颗粒） for low myopia in children with heart yang insufficiency. MethodsA multicentre， prospective， double-blind randomised controlled study was conducted， in which 290 children with low myopia from 8 centres were randomly divided into 145 cases in the treatment group and 145 cases in the control group， and the treatment group was given education， dispensing glasses， and Chinese herbal medicine Mingshi Granules， while the control group was given education， dispensing glasses， and granules placebo. Both Mingshi Granules and placebo granules were taken orally， 1 bag each time， twice daily， 4 weeks of oral intake and 2 weeks of rest as 1 course of treatment， a total of 4 courses of treatment （24 weeks）. Equivalent spherical lenses， best naked-eye distance visual acuity， ocular axis， corneal curvature K1， adjustment amplitude， traditional Chinese medicine （TCM） symptom scores， calculate the amount of progression of equivalent spherical lenses， were observed at the 12th and the 24th week of treatment， at the 36th week and 48th week of follow-up， resectively， the control rate of myopia progression was evaluated at the 24th week， and safety indexes were observed before treatment. ResultsThe amount of progression of equivalent spherical lenses was lower in the treatment group than in the control group at the 48-week follow-up （P＜0.05）. The control rate of myopia progression at 24 weeks after treatment in the treatment group was higher （57.60%， 72/125） than that in the control group （44.63%， 54/121） （P＜0.05）. The best naked-eye distance visual acuity at 36-week follow-up in the treatment group was higher than that in the control group （P＜0.05）. Equivalent spherical lenses were significantly lower in both groups at all observation time points compared with pre-treatment （P＜0.05）， and were higher in the treatment group than in the control group at the 48-week follow-up （P＜0.05）. The ocular axes of both groups were significantly higher at each observation time point after treatment and at follow-up compared with before treatment （P＜0.05）. The amount of eye axis growth in the treatment group was lower than that in the control group at 24 weeks after treatment and at the 48-week follow-up （P＜0.05）. Corneal curvature K1 was significantly lower in the treatment group at the 24th week of treatment compared to pre-treatment （P＜0.05）. The magnitude of adjustment in the treatment group was significantly higher at the 36-week follow-up and at the 48-week follow-up than before treatment （P＜0.05）. The scores of white/dark complexion， white coating thin pulse， fatigue and total TCM symptom scores of children in both groups at the 12th， 24th， 36th and 48th weeks of follow-up were significantly lower than those before treatment （P＜0.05）； the scores of blurred vision at the 24th and 36th weeks of follow-up were significantly lower than those before treatment （P＜0.05）； and the scores of blurred vision in the treatment group at the 48th week of follow-up were signi-ficantly lower than those before treatment （P＜0.05）. In the treatment group， the score of fatigue was higher than that of the control group at the 36-week follow-up， and the score of blurred vision was lower than that of the control group at the 48-week follow-up （P＜0.05）. No adverse reactions or obvious abnormalities of the safety indexes were observed of the two groups during the treatment. ConclusionChinese herbal medicine Mingshi Granules showed the effect of controlling the progression of low myopia， improving the best naked eye distance visual acuity， slowing down the growth of the eye axis， improving some of the TCM symptoms， with good safety.

Objective To evaluate the change of energy metabolism during cisplatin-induced acute kidney injury.Methods Adult CD-1 male mice were intraperitoneally injected with a single dose of cisplatin (20 mg/kg), and renal function and renal tissue pathology were tested;gene expression was analyzed and signaling pathways were en-riched in cisplatin-treated renal tubular epithelial cells using transcriptome; the contents of renal glycolysis and a-mino acid metabolites were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) .Re-sults Serum urea nitrogen and blood creatinine significantly increased in cisplatin-treated mice.Pathological his-tology observed swelling and shedding of renal tubular epithelial cells.Transcriptome analysis revealed that 2632 genes were upregulated and 2799 genes were downregulated in cisplatin-treated HK-2 cells.GO and KEGG analy-sis showed that differential genes were enriched in energy metabolism.The GSEA analysis results showed that cispl-atin caused an upregulation of the oxidative phosphorylation pathway and a downregulation of the glycolysis pathway in renal tubular epithelial cells, further KEGG analysis demonstrated that cisplatin caused changes in the expression of amino acid genes in renal cells.Metabolomics showed that the contents of glycolytic intermediates and several a-mino acids were altered in the kidney of cisplatin-treated mice.Conclusion Cisplatin-induced acute renal injury is accompanied by modification in renal tubular cell glycolysis and amino acid metabolism.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

The acupoint sensitization theory,a breakthrough in acupuncture and moxibustion over the past two decades,has greatly enhanced the understanding of meridians and acupoints while increasing the effectiveness of clinical diagnosis and treatment in acupuncture and moxibustion practices.The number of studies on surface sensitization site detection for different diseases is increasing.However,systematic sorting and a summary of the detection mode of surface sensitization points are lacking.Therefore,this study categorizes the method of surface sensitization point detection into two modes:pan-scanning and focused scanning.The classification is based on the characteristics of the openness of the research purpose,the precision of the target range,and the degree of variation during detection.The two modes have considerable differences in the exploration efficiency and the presentation of result.The pan-scanning mode can be further subdivided into holistic and localized pan-scanning modes,whereas the focused-scanning mode can be subdivided into fixed-and variable-focused scanning modes.This study analyzes the application scenarios,characteristics,advantages,and limitations of each detection mode and presents opinions on mode selection,mode innovation,and future development directions.This study aims to provide valuable insights and guidance for the follow-up research on surface sensitization site detection of various diseases.

Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

Objective To analyze the prevalence of chronic diseases and its influencing factors of dust-exposed male workers in a coal mine. Methods A total of 9 782 dust-exposed male workers from a coal mine in Shanxi Province were selected as the study subjects using the purposive sampling method. Their occupational health examination results were collected to analyze the prevalence of chronic diseases and its influencing factors. Results The prevalence of dyslipidemia, hyperuricemia, hypertension and diabetes were 40.3%, 30.7%, 23.5% and 5.6%, respectively. The prevalence of chronic diseases was 64.8%. Among them, the prevalence of having one, two, three or more chronic diseases were 36.5%, 21.6% and 6.7%, respectively. The prevalence of comorbid chronic diseases was 28.3%, with the highest prevalence of concurrent dyslipidemia and hyperuricemia of 11.0%. The results of binary logistic regression analysis showed that the risk of chronic disease was higher in workers <40 years old, smoking, overweight, obesity and total working years >20 years (all P<0.05). The results of multinomial logistic regression analysis showed that workers <40 years old, overweight, obesity and total working years >20 years were risk factors for having one chronic disease (all P<0.05). The workers <40 years old, smoking, overweight, obesity and total working years >20 years were risk factors for having two chronic diseases (all P<0.05). The workers <40 years old, smoking, alcohol consumption, overweight, obesity, other types of work, and working years >20 years were risk factors for having three or more chronic diseases (all P<0.05). Conclusion The prevalence of chronic diseases is high and the comorbidity of chronic diseases is common among dust-exposed male workers. The main influencing factors were age, smoking, alcohol consumption, overweight, obesity, type of work, and working year. Workers with more contributing factors have higher risk of chronic comorbidities.