The structure of N-glycans on specific proteins can regulate innate and adaptive immunity via sensing environmental signals. Meanwhile, the structural diversity of N-glycans poses analytical challenges that limit the exploration of specific glycosylation functions. In this work, we used THP-1-derived macrophages as examples to show the vast potential of a N-glycan structural interpretation tool StrucGP in N-glycoproteomic analysis. The intact glycopeptides of macrophages were enriched and analyzed using mass spectrometry (MS)-based glycoproteomic approaches, followed by the large-scale mapping of site-specific glycan structures via StrucGP. Results revealed that bisected GlcNAc, core fucosylated, and sialylated glycans (e.g., HexNAc₄Hex₅Fuc₁Neu5Ac₁, N₄H₅F₁S₁) were increased in M1 and M2 macrophages, especially in the latter. The findings indicated that these structures may be closely related to macrophage polarization. In addition, a high level of glycosylated PD-L1 was observed in M1 macrophages, and the LacNAc moiety was detected at Asn-192 and Asn-200 of PD-L1, and Asn-200 contained Lewis epitopes. The precision structural interpretation of site-specific glycans and subsequent intervention of target glycoproteins and related glycosyltransferases are of great value for the development of new diagnostic and therapeutic approaches for different diseases.
Humans ; B7-H1 Antigen ; Glycosylation ; Polysaccharides/metabolism*

Objective:To observe the changes of optic disc structure in patients with high myopia and the correlation with the morphological markers of the fundus.Methods:A retrospective study. From July 2018 to January 2020, 90 patients (155 eyes) diagnosed as high myopia in Department of Ophthalmology of Beijing Friendship Hospital affiliated to Capital Medical University were included in the study. Among them, there were 31 males (52 eyes) and 59 females (103 eyes), with age of 57.1±14.2 years old and axial length (AL) of 28.5±2.6 mm. According to the classification of myopic macular degeneration, patients were divided into 4 groups based on forms and degree of lesions, including non-pathological myopia group, mild traction lesions group, severe traction lesions group and neovascular lesions group, 35, 58, 41, 21 eyes, respectively. The digitized fundus photographs and an Image J system were used to measure the horizontal, vertical, maximal, and minimal diameter of the optic disc, the horizontal and vertical diameter of the parapapillary δ zone and γ zone, ovality index, distance between the most superior point of the temporal superior arterial arcade and most inferior point of the temporal inferior arterial arcade (VDA), angle between the temporal arterial arcade and optic disc (angle kappa), distance between the optic disc center and the fovea (DFD), angle between the horizontal disc axis and the disc-fovea line (DFA). The correlation between the diameter of the optic disc and other parameters was analyzed. Univariate and multivariate analysis were used to compare differences between groups.Results:The horizontal diameter of the optic disc was positively correlated with the horizontal diameter of the δ zone ( r=0.300, P<0.001), Kappa angle ( r=0.260, P=0.003), and elliptic index ( r=0.650, P<0.001); it was negatively correlated with DFD ( r=-0.190, P=0.030). Optic disc vertical diameter and optic disc horizontal diameter ( r=0.280), δ-zone horizontal diameter ( r=0.330) and vertical diameter ( r=0.460), γ-zone horizontal diameter ( r=0.430) and vertical diameter ( r=0.390), DFD ( r=0.390) was positively correlated ( P<0.001); it was negatively correlated with DFA ( r=-0.210, P=0.001) and Kappa angle ( r=-0.210, P=0.004). Compared with the non-pathological myopia group, there were statistically significant differences in the horizontal and vertical diameters of the optic disc in the severe traction disease group ( P<0.05). Among them, the horizontal diameter difference did not depend on the eye axis and age difference; the vertical diameter difference was caused by the eye axis difference. Compared with the non-pathological myopia group, the difference in the horizontal diameter of the optic disc in the neovascular disease group was statistically significant ( P<0.05), and did not depend on the difference in the axis and age; the difference in the vertical diameter of the optic disc was not statistically significant ( P>0.05). Conclusion:The morphology of optic disc was related to several fundus morphological markers, which was differentiated according to the age, AL and the degree of disease in patients with high myopia.

Macrophages are widely distributed immune cells that contribute to tissue homeostasis. Human THP-1 cells have been widely used in various macrophage-associated studies, especially those involving pro-inflammatory M1 and anti-inflammatory M2 phenotypes. However, the molecular characterization of four M2 subtypes (M2a, M2b, M2c, and M2d) derived from THP-1 has not been fully investigated. In this study, we systematically analyzed the protein expression profiles of human THP-1-derived macrophages (M0, M1, M2a, M2b, M2c, and M2d) using quantitative proteomics approaches. The commonly and specially regulated proteins of the four M2 subtypes and their potential biological functions were further investigated. The results showed that M2a and M2b, and M2c and M2d have very similar protein expression profiles. These data could serve as an important resource for studies of macrophages using THP-1 cells, and provide a reference to distinguish different M2 subtypes in macrophage-associated diseases for subsequent clinical research.
Humans ; Macrophages/metabolism* ; Phenotype ; Proteomics ; THP-1 Cells

Objective:To preliminarily estimate and study the effect of nucleic acid testing in blood screening on the residual risk (RR) of transfusion transmitted HBV infection (TTI HBV).Methods:Using the NAT yield/WP ratio model and adopting the relevant data of information management system of practice comparison working party in the Mainland of China, this paper analyzed the trend of the RR of TTI HBV among 18 blood centers from 2015 to 2019 in China, and compared the impact of two kinds of blood screening strategies which were ELISA+ ID-NAT/MP-NAT (individual-donation nucleic acid testing or mini-pool nucleic acid testing) and ELISA + MP-NAT on RR in 2019.Results:The overall trends of the 5-year RR of HBV among 18 blood centers showed by trend chi square test were NAT single positive rate trend χ2= 39.42( P<0.01) and residual risk trend χ2= 279.792( P<0.01); The influence on RR from the differences of ELISA+ ID-NAT/MP-NAT and ELISA+ MP-NAT was statistically significant, and chi square test showed that χ2= 7.4( P<0.01). Conclusions:Since the implementation of nucleic acid testing in the blood screening in China from 2015, the residual risk of transfusion transmitted HBV infection has decreased year by year. The observed two blood screening strategies which dominated in China may lead to discrepancy in the residual risk of TTI.

Objective:To clarify the effect and related factors of antiviral therapy on the change of esophageal varices in patients with hepatitis B virus-related cirrhosis.Methods:Fifty-two cases with hepatitis B virus-related cirrhosis who underwent endoscopy before and after antiviral therapy were selected from prospective cohorts. Patients were divided into three groups: no, mild, and moderate-severe based on the degree of esophageal varices. The changes in the severity of esophageal varices in each group were compared after antiviral therapy. Clinical characteristics (platelet, liver and kidney function, liver stiffness, and virological response) of patients with different regressions were analyzed. Measurement data were analyzed by independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test, and Chi-Square test was used for count data.Results:All patients received entecavir-based antiviral therapy. The median treatment time was 3.1 (2.5-4.4) years. The proportion of patients without esophageal varices increased from 30.8% to 51.9%, the proportion of mild esophageal varices decreased from 40.4% to 30.8%, and the proportion of patients with moderate-to-severe esophageal varices decreased from 28.8% to 17.3% ( χ2=14.067, P=0.001). A total of 40.4% of patients had esophageal varices regression, and 13.5% had esophageal varices progression. The progression rate was significantly higher in patients with moderate-severe esophageal varices than patients with mild and no esophageal varices ( χ2=28.126, P<0.001), and 60.0% of patients with moderate-severe esophageal varices still remained in moderate-severe state after antiviral treatment. Baseline platelet count and 5-year mean change rates were significantly lower in patients with progressive moderate-to-severe esophageal varices than in those without progression (+3.3% vs. +34.1%, Z=7.00, P=0.027). Conclusion:After effective antiviral treatment, 40.4% of patients with hepatitis B virus-related cirrhosis combined with esophageal varices has obtained esophageal varices regression, but those with moderate to severe esophageal varices still have a considerable risk of progression while receiving mono antiviral treatment only. Thrombocytopenia and without significant improving are the clinical signs of progression risk after receiving antiviral treatment.

Objective: To investigate the genetic characteristics of Lamivudine-resistant mutation patterns and HBV S gene mutants in patients with chronic hepatitis disease of different disease progression. Methods: Blood samples of LAM-resistant patients with chronic hepatitis disease were collected. HBV RT gene nucleotide sequences were obtained, and then differences in drug-resistant mutation patterns, drug susceptibility and HBV S gene mutants characteristics between the two groups were analyzed. Results: Forty-seven chronic hepatitis B (CHB) patients and 16 HBV-related liver cirrhosis (LC)/HBV-related hepatocellular carcinoma (HCC) patients were included in this study. M204I single point mutation and L180M+ M204I/V were the most common pattern during patients with chronic hepatitis disease (35/63, 55.56%). The numbers of resistant to three nucleos(t)ide analogues in LC/HCC group was higher than CHB group’s (62.50% vs 34.04%, P=0.046). In HBV S gene, more immune associated HBsAg-escape mutations were detected in LC/HCC group than that in CHB group (62.50% vs 31.91%, P=0.031). I126T/V and G145A (for LCC/HCC group, 60%), I126S/T and S117T (for CHB group, 46.67%) were showed as the most common form for HBsAg escape mutations in the two groups. The two groups both detected RT mutations concomitantly with stop codon mutations in S gene (rtA181T/sW172* and rtM204I/sW196*). Conclusions Different characteristics in Lamivudine-resistant mutations and associated HBV S gene mutants were found in patients with chronic hepatitis disease of different disease progression, and LC/HCC patients exhibit more multi-drug resistant variants and immune associated HBsAg-escape mutants than CHB patients.

Objective To understand the association between pregnancy intention and pregnancy-related anxiety in the second and third trimester and its strength.Methods A prospective cohort study was conducted in Ma' anshan,Anhui province.A total of 3 474 eligible pregnant women within 14 weeks of gestation were recruited.The information about their demographic characteristics were collected in early pregnancy.The completed questionnaire of pregnancy-related anxiety were asked to return in the second and third trimester.Logistic regression analysis was conducted to evaluate the association between pregnancy intention and pregnancy-related anxiety in the second and third trimester.Results A total of 3 083 pregnant women were included in final analysis,The rate of unintentional pregnancy was 15.00％ (n=461).The detection rates of pregnancy-related anxiety in the second and third trimester were 29.13％ (n=898) and 30.36％ (n=936).After controlling potential confounding factors,unintentional pregnancy increased the risk of pregnancy-related anxiety in the second trimester compared with intentional pregnancy (OR=1.85,95％ CI:1.44-2.38);The risk of pregnancy-related anxiety also increased in the third trimester (OR=1.84,95％ CI:1.44-2.35).Intentional pregnancy did not increase the risk of pregnancy-related anxiety in the second and third trimester.Conclusion The study results suggests that unintentional pregnancy could increase the risk of pregnancy-related anxiety in the second and third trimester.

Objective To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with severe dysmenorrhea in a prospective cohort study. Methods From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients′parameters were recorded prospectively, including symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, carrying status of LNG-IUS, menstruation patterns and adverse effects. Changes of scores and patterns of pain during follow-up were analyzed. Results Totally 1 100 women meets inclusion criteria, among which 640 cases (58.18%, 640/1 100) had severe dysmeorrhea, with median follow-up period of 35 months (range 1-60 months), and accumulative carrying rate of 65% at 60 months follow-up. After placement of LNG-IUS, scores of pain and ratio of severe dysmenorrhea had decreased significantly compared with baselines (all P<0.01), the scroes of visual analog scale (VAS) were 8.1 ± 0.9, 5.5 ± 2.4, 4.6 ± 2.4, 3.3 ± 2.2, 2.2 ± 2.1, 2.2 ± 1.8, 1.4 ± 1.6 and 1.3 ± 1.3 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 36 months after placement of LNG-IUS, scores of pain had improved significantly compared with preceding period (all P<0.01). We found no universal dependent factors predicting improvement of pain, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). Conclusion LNG-IUS is effective for adenomyosis of severe dysmenorrhea. Improvement of pain is independent on patients characters, menstruation patterns or adverse effects.

Objective To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system (LNG-IUS) for symptomatic adenomyosis in a prospective cohort study. Methods From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients′ parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results Totally 1 100 cases met inclusion criteria, with median age 36 years (range 20-44 years), median follow-up 35 months (range 1-108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383) and 29.6%(82/277) patients achieved amenorrhea respectively (P<0.01). Total and subclassification of adverse effects decreased significantly (P<0.01). Within 12 months and >12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status (all P>0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of menstruation patterns or adverse effects neither have any risk factor nor have impact on treatment effects.