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.

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.

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 investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective To establish an index system for assessing the quality of hospital accreditation data and determine the hierarchical weights of indices at different levels,providing a reference for enhancing the governance of such data.Methods A quality assessment system for hospital accreditation data was developed using literature analysis method and Delphi method.The analytic hierarchy process was employed to create a pairwise comparison judgment matrix to determine the weights of indices.Results An evaluation system was constructed with the following levels:"Indicator Screening Quality-Data Reporting Quality-Data Quality Control Quality-Data On-Site Verification Quality."The system includes 4 first-level indicators and 18 second-level indicators.The indicator with the highest weight among the first-level indicators was Data Reporting Quality(0.496 5),followed by Data Quality Control Quality(0.313 2).Among the second-level indicators,Timeliness(0.428 6)and Cooperation(0.428 6)had the highest weights.Conclusion The establishment of the quality evaluation system of hospital accreditation da-ta is a strategy to optimize the control of hospital accreditation data quality and is beneficial for continuous improvement of hospital accreditation data quality.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective:To investigate the relationship and clinical significance of circulating tu-mor DNA(ctDNA)methylation with postoperative recurrence of thyroid cancer.Method:5 pa-tients with recurrent thyroid cancer in our hospital from March 2021 to April 2022 were selected as the observation group,and 2 healthy volunteers were selected as the control group.The level of ctDNA methylation in peripheral blood of the two groups was detected by Illumina high-throughput sequencing system.Gene ontology(GO)function analysis and Kyoto gene and genome encyclope-dia(KEGG)signal pathway analysis were carried out on the methylation region genes with signifi-cant differences through the DAVID gene function analysis platform.Result:There were 7787 dif-ferential ctDNA methylation sites between the two groups.2914(37.4％)were hypermethylation sites and 4873(62.6％)were low methylation sites.GO functional analysis showed that differentially methylated genes were enriched in molecular functions such as DNA-binding transcriptional acti-vation,cell-substrate adhesion,glycoprotein complex and other cellular components.KEGG path-way analysis showed that differentially methylated genes were enriched in thyroid carcinoma signal pathway,cell adhesion molecules,RAP1 signal pathway,RAS signal pathway,MAPK signal path-way and so on.Conclusion:ctDNA methylation may be involved in cancer recurrence in postop-erative patients with thyroid cancer.Monitoring the level of ctDNA methylation in peripheral blood may be an effective method to indicate the recurrence or metastasis of thyroid cancer and guide clinical diagnosis and treatment.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

Objective:To investigate the characteristics, diagnosis and therapeutic effect of acquired lymphangiectasia of the vulva (ALV).Methods:A retrospective analysis of clinicopathological and follow-up data was conducted on the patients treated in Capital Medical University Affiliated Beijing Shijitan Hospital due to female ALV from July 2009 to July 2023. The patients who completed the staged operations [partial labiectomy and reconstruction + thoracic ductplasty and (or) perineal lymphovenous anastomosis] were included in the study and followed up. The improvement of perineal swelling, blister range, fluid leakage volume and frequency were evaluated through outpatient visits by the symptom rating scale of ALV (hereinafter referred to as the symptom rating scale) before and after surgery.Results:A total of 48 patients were treated due to ALV from July 2009 to July 2023, of which 98% (47/48) were postoperative pelvic malignant tumors and 94% (45/48) had a history of radiotherapy. A total of 10 patients with ALV who completed the staged operations were included in this study. (1) Clinical characteristics and diagnosis: 10 patients had a median age of 60 years old (50, 63 years old ). The median duration from cervical cancer surgery and radiation therapy to vulvar swelling was 1.5 years (0.0, 2.0 years), and the median duration from vulvar swelling to blister formation and leakage was 0.0 years (0.0, 4.8 years). Seven patients (7/10) had a history of recurrent erysipelas; 7 patients (7/10) had the most severe symptom (widespread blisters, persistent fluid leakage, and large amount of fluid leakage); noncontrast magnetic resonance lymphography (NCMRL) showed edema signals in the perineal region of all the patients, and increase of agent in the perineal region was observed in lymphoscintigram (LS). (2) Surgical treatment and postoperative pathological examination: of the 10 ALV patients who completed staged surgical treatment, 6 cases (6/10) were diagnosed with thoracic duct outlet obstruction and underwent thoracic ductplasty and partial labiectomy and reconstruction. Perineal lymphovenous anastomosis and partial labiectomy and reconstruction were performed in 4 cases (4/10) without thoracic duct outlet obstruction. Postoperative routine pathological examination of 10 patients (10/10) showed dermal papilla lymphangiectasia. Immunohistochemical tests were performed on 5 patients, all of which were positive for D2-40 and negative for CD 34. (3) Efficacy: 8 patients completed the postoperative follow-up, and the median follow-up time was 31.0 months (17.5, 78.3 months). The perineal swelling and the blister fluid leakage were all significantly improved after the staged operations. All indexes of the symptom rating scale, including the degree of perineal swelling, blister range, fluid leakage volume and frequency, were significantly improved in 8 follow-up patients, and 3 (3/8) of them were cured; the median symptom score decreased significantly from 11.0 before surgery to 3.0 after surgery ( P<0.001). The incidence of erysipelas was significantly reduced from 7/10 before surgery to 2/8 after surgery ( P=0.035). Conclusions:The main causes of female ALV are pelvic tumor surgery and radiotherapy. The clinical diagnosis is made from relevant medical history, clinical manifestations, LS and magnetic resonance imaging. The diagnosis is confirmed by histopathological findings. Pathological results show lymphangiectasia in the dermal papilla, and immunohistochemical staining show positive for D2-40 and negative for CD 34. The effect of staged surgery on ALV is remarkable and even cured, and could effectively reduce the incidence of erysipelas.